Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Authorised, recruiting
Participants planned
79
Countries
8
Sites
14
Type 3 Von Willebrand Disease
To evaluate the efficacy of prophylactic emicizumab (i.e., administered on a scheduled basis with the intent to prevent bleeds) over time compared with on-demand standard of care (SOC) based on the superiority assessment of the following primary endpoint
Key facts
- Sponsor
- F. Hoffmann-La Roche AG
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 4 Jun 2025 → ongoing
- Decision date (initial)
- 2025-05-05
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- F. Hoffmann-La Roche AG
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Pharmacokinetic, Others
To evaluate the efficacy of prophylactic emicizumab (i.e., administered on a scheduled basis with the intent to prevent bleeds) over time compared with on-demand standard of care (SOC) based on the superiority assessment of the following primary endpoint
Secondary objectives 5
- To evaluate the efficacy of prophylactic emicizumab over time compared with on-demand and/or prophylactic SOC based on the assessment of the following secondary efficacy endpoints
- To evaluate the overall safety and tolerability of prophylactic emicizumab in participants with Type 3 von Willebrand disease
- To characterize the emicizumab pharmacokinetics in patients with Type 3 von Willebrand Disease
- To evaluate the immune response of emicizumab
- To evaluate the quality of life in participants with Type 3 von Willebrand disease
Conditions and MedDRA coding
Type 3 Von Willebrand Disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 27.1 | PT | 10047715 | Von Willebrand´s disease | 100000004850 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | A PHASE III, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE EFFICACY, SAFETY, PHARMACOKINETICS, AND P This is a phase III, multicentre, open-label clinical study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab prophylaxis in participants aged 2 years and above, who have been diagnosed with Type 3 VWD. Participants on prior SOC on-demand therapy will be assessed via a randomized comparison (Arms A and B), while participants on prior SOC prophylactic therapy (Arm C) will be assessed via intrapatient analysis with data obtained from the preceding non-interventional study (NIS: WP45335).
A NIS (WP45335), preceding this Phase III interventional study, has been initiated to document the number, location, and types of bleeds, and current treatment with prophylactic SOC VWD treatments, and safety in participants with Type 3 VWD. The assessments in the NIS will ensure consistency in bleed reporting between the NIS and the interventional study, and the resulting data will serve as a source of comparator information for key analyses conducted in this Phase III clinical study. In addition, the NIS will enable earlier identification and confirmation of participants who may qualify for this Phase III clinical study. It is anticipated that the majority of participants in WP45335 will enrol in this study, as long as they maintain the same SOC treatment regiment with appropriate exposure as per local label or treatment guidelines during the 24-week continued observational period in the NIS. Participants will be specifically required to have adhered to at least 80% of prescribed doses as per label or local treatment guidelines during the period of the NIS to qualify to enter Arm C of this study, meet the inclusion and exclusion criteria of this Phase III clinical study, and are able to enrol at a participating site while the study is open for enrolment.
|
Not Applicable | None | A: Prior SOC On-demand: participants taking ondemand SOC at the time of study entry (and for at least 24 weeks prior to enrollment) Treatment in this Phase III : Emicizumab prophylaxis B: Prior SOC On-demand: participants taking ondemand SOC at the time of study entry (and for at least 24 weeks prior to enrollment) Treatment in this Phase III: On-demand SOC for 24 weeks, then switch to emicizumab prophylaxis at study extension phase C: Prior SOC Prophylaxis: Participants taking SOC prophylactic treatment at the time of study entry and for at least 24 weeks of observation during the preceding NIS Study WP45335 Treatment in this Phase III: Emicizumab prophylaxis |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- EMA paediatric investigation plan (PIP)
- EMEA-000018-PIP10-43
- Plan to share IPD
- No
- IPD plan description
- n/a
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Age ≥ 2 years at the time of signing Informed Consent/Assent Form (Arm C)
- Adequate hematological function
- Documented exposure to on-demand and prophylactic SOC
- For patient with childbearing potential; agreement to adhere to the contraception requirements
- Confirmed diagnosis of Type 3 VWD, based on evaluation of VWF and FVIII levels
- Age ≥ 1 month at the time of signing Informed Consent/Assent Form (Arms A and B)
Exclusion criteria 5
- Inherited or acquired bleeding disorder other than Congenital Type 3 VWD
- History of intracranial hemorrhage
- Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
- Other conditions (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
- History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Number of treated bleeds over time
Secondary endpoints 14
- Number of all bleeds over time
- Number of treated spontaneous bleeds over time
- Number of treated joint bleeds over time
- Incidence and severity of adverse events
- Incidence and severity of thromboembolic events
- Incidence and severity of thrombotic microangiopathy events
- Incidence and severity of injection-site reactions
- Incidence of adverse events leading to drug discontinuation
- Incidence of severe hypersensitivity, anaphylaxis, or anaphylactoid reactions
- Changes from baseline in physical examination findings, vital signs, and ECG parameters
- Incidence of laboratory abnormalities
- Trough plasma concentration of emicizumab
- Prevalence and incidence of ADAs to emicizumab
- Change from baseline in Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Hemlibra 150 mg/mL solution for injection
PRD5960585 · Product
- Active substance
- Emicizumab
- Substance synonyms
- RO5534262, ACE910
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BX06 — -
- Marketing authorisation
- EU/1/18/1271/004
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Re-labeled for Clinical Trial Use
Comparator 26
Wilate 1000, 1000 IU VWF/1000 IUFVIII, powder and solvent for solution for injection
PRD326465 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- PL 10673/0038
- MA holder
- OCTAPHARMA-LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Wilate 500, 500 IU VWF/500 IUFVIII, powder and solvent for solution for injection
PRD326466 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- PL 10673/0038
- MA holder
- OCTAPHARMA-LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Willfact 2000 IU Powder and solvent for solution for injection
PRD2875591 · Product
- Active substance
- Human Von Willebrand Factor
- Substance synonyms
- HUMAN PLASMA-DERIVED VON WILLEBRAND FACTOR
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD10 — -
- Marketing authorisation
- PL 28315/0007
- MA holder
- LFB BIOMEDICAMENTS
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
VEYVONDI 1300 IU powder and solvent for solution for injection.
PRD6590238 · Product
- Active substance
- Vonicog Alfa
- Substance synonyms
- Recombinant human von Willebrand factor
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD10 — -
- Marketing authorisation
- EU/1/18/1298/002
- MA holder
- BAXALTA INNOVATIONS GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
VEYVONDI 650 IU powder and solvent for solution for injection.
PRD6590056 · Product
- Active substance
- Vonicog Alfa
- Substance synonyms
- Recombinant human von Willebrand factor
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD10 — -
- Marketing authorisation
- EU/1/18/1298/001
- MA holder
- BAXALTA INNOVATIONS GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
FEIBA 50 U/ml powder and solvent for solution for infusion
PRD3234144 · Product
- Active substance
- Factor Viii Inhibitor Bypassing Fraction
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD03 — FACTOR VIII INHIBITOR BYPASSING ACTIVITY
- Marketing authorisation
- PL 34078/0003
- MA holder
- BAXALTA INNOVATIONS GMBH
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fanhdi 500 IU powder and solvent for solution for injection.
PRD360177 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- PA0849/001/002
- MA holder
- INSTITUTO GRIFOLS, S.A.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11321358 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- 1997095755
- MA holder
- CSL BEHRING GMBH
- MA country
- Luxembourg
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11321356 · Product
- Active substance
- Human Von Willebrand Factor
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- 1997095756
- MA holder
- CSL BEHRING GMBH
- MA country
- Luxembourg
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11321357 · Product
- Active substance
- Human Von Willebrand Factor
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- 1987095757
- MA holder
- CSL BEHRING GMBH
- MA country
- Luxembourg
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 1500 IU Powder and solvent for solution for injection
PRD3961065 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/005
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 1000 IU Powder and solvent for solution for injection
PRD3961045 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/004
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 250 IU Powder and solvent for solution for injection
PRD3960817 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/001
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 750 IU Powder and solvent for solution for injection
PRD3960978 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/003
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 3000 IU Powder and solvent for solution for injection
PRD6601850 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/007
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 2000 IU Powder and solvent for solution for injection
PRD3961084 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/006
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 4000 IU powder and solvent for solution for injection
PRD6832304 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/008
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELOCTA 500 IU Powder and solvent for solution for injection
PRD3960959 · Product
- Active substance
- Efmoroctocog Alfa
- Substance synonyms
- Recombinant fusion protein consisting of human coagulation factor VIII attached to the Fc domain of human IgG1, BIIB031
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/15/1046/002
- MA holder
- SWEDISH ORPHAN BIOVITRUM AB (PUBL)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7945682 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- EU/1/13/857/003
- MA holder
- CSL BEHRING GMBH
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7945683 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- EU/1/13/857/004
- MA holder
- CSL BEHRING GMBH
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7945680 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- EU/1/13/857/001
- MA holder
- CSL BEHRING GMBH
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7945681 · Product
- Active substance
- Human Coagulation Factor Viii
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD06 — VON WILLEBRAND FACTOR AND COAGULA-TION FACTOR VIII IN COMBINATION
- Marketing authorisation
- EU/1/13/857/002
- MA holder
- CSL BEHRING GMBH
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
NovoSeven 8 mg (400 KIU) powder and solvent for solution for injection
PRD3583263 · Product
- Active substance
- Eptacog Alfa (Activated)
- Substance synonyms
- Recombinant human coagulation Factor VIIa, rFVIIa, EPTACOG ALFA
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD08 — EPTACOG ALFA (ACTIVATED)
- Marketing authorisation
- EU/1/96/006/011
- MA holder
- NOVO NORDISK A/S
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
NovoSeven 5 mg (250 KIU) powder and solvent for solution for injection
PRD3583261 · Product
- Active substance
- Eptacog Alfa (Activated)
- Substance synonyms
- Recombinant human coagulation Factor VIIa, rFVIIa, EPTACOG ALFA
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD08 — EPTACOG ALFA (ACTIVATED)
- Marketing authorisation
- EU/1/96/006/010
- MA holder
- NOVO NORDISK A/S
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
NovoSeven 1 mg (50 KIU) powder and solvent for solution for injection
PRD3583255 · Product
- Active substance
- Eptacog Alfa (Activated)
- Substance synonyms
- Recombinant human coagulation Factor VIIa, rFVIIa, EPTACOG ALFA
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD08 — EPTACOG ALFA (ACTIVATED)
- Marketing authorisation
- EU/1/96/006/008
- MA holder
- NOVO NORDISK A/S
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
NovoSeven 2 mg (100 KIU) powder and solvent for solution for injection
PRD3583257 · Product
- Active substance
- Eptacog Alfa (Activated)
- Substance synonyms
- Recombinant human coagulation Factor VIIa, rFVIIa, EPTACOG ALFA
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD08 — EPTACOG ALFA (ACTIVATED)
- Marketing authorisation
- EU/1/96/006/009
- MA holder
- NOVO NORDISK A/S
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 4
ADVATE 1 500 IU/2 ml powder and solvent for solution for injection
PRD8047980 · Product
- Active substance
- Octocog Alfa
- Substance synonyms
- Octocog alpha, OCTOCOG ALFA (GENETICAL RECOMBINATION)
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/03/271/020
- MA holder
- TAKEDA MANUFACTURING AUSTRIA AG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ADVATE 1 500 IU/2 ml powder and solvent for solution for injection
PRD8047969 · Product
- Active substance
- Octocog Alfa
- Substance synonyms
- Octocog alpha, OCTOCOG ALFA (GENETICAL RECOMBINATION)
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/03/271/020
- MA holder
- TAKEDA MANUFACTURING AUSTRIA AG
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ADVATE 1 500 IU/2 ml powder and solvent for solution for injection
PRD8047971 · Product
- Active substance
- Octocog Alfa
- Substance synonyms
- Octocog alpha, OCTOCOG ALFA (GENETICAL RECOMBINATION)
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/03/271/020
- MA holder
- TAKEDA MANUFACTURING AUSTRIA AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ADVATE 1 500 IU/2 ml powder and solvent for solution for injection
PRD8047975 · Product
- Active substance
- Octocog Alfa
- Substance synonyms
- Octocog alpha, OCTOCOG ALFA (GENETICAL RECOMBINATION)
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0 DF dosage form
- Max total dose
- 0 DF dosage form
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/03/271/020
- MA holder
- TAKEDA MANUFACTURING AUSTRIA AG
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
F. Hoffmann-La Roche AG
- Sponsor organisation
- F. Hoffmann-La Roche AG
- Address
- Grenzacherstrasse 124
- City
- Basel
- Postcode
- 4058
- Country
- Switzerland
Scientific contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Public contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Third parties 6
| Organisation | City, country | Duties |
|---|---|---|
| BioAgilytix Europe GmbH ORG-100016335
|
Hamburg, Germany | Other |
| Almac Clinical Technologies LLC ORG-100043036
|
Souderton, United States | Other |
| Eresearchtechnology Inc. ORG-100013039
|
Philadelphia, United States | Other |
| Medpace Reference Laboratories LLC ORG-100041727
|
Cincinnati, United States | Other |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Other |
| QPS Netherlands B.V. ORG-100009393
|
Groningen, Netherlands | Other |
Locations
8 EU/EEA countries · 14 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 5 | 1 |
| France | Ongoing, recruiting | 4 | 2 |
| Germany | Ongoing, recruiting | 13 | 3 |
| Italy | Ongoing, recruiting | 6 | 3 |
| Netherlands | Ongoing, recruiting | 5 | 1 |
| Poland | Ongoing, recruiting | 3 | 1 |
| Spain | Authorised, recruiting | 7 | 2 |
| Sweden | Authorised, recruitment pending | 4 | 1 |
| Rest of world
South Africa, United Kingdom, United States, Colombia, Japan, Canada
|
— | 32 | — |
Investigational sites
Hopital Necker Enfants Malades
Service d'hématologie adulte, 149 Rue De Sevres, 75015, Paris
Centre Hospitalier Universitaire De Lille
Hémostase Clinique, Boulevard Du Professeur Jules Leclercq, 59000, Lille
Universitaetsklinikum Bonn AöR
Institut für Experimentelle Hämatologie und Transfusionsmedizin Gebäude B 42, Venusberg-Campus 1, Venusberg, Bonn
Universitaetsklinikum Frankfurt AöR
Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Gerinnungszentrum Rhein-Ruhr Aerztepartnerschaft Dr. med. Hannelore Rott Fachaerztin fuer Transfusionsmedizin Haemostaseologie Dr. med. Susan Halimeh Fachaerztin fuer Transfusionsmedizin Haemostaseologie Dr. med. Guenther Kappert Facharzt fuer Laboratoriumsmedizin Haemostaseologie
Gerinnungszentrum Rhein-Ruhr, Koenigstrasse 13, Altstadt, Duisburg
Azienda Ospedaliero Universitaria Careggi
Centro Malattie Emorragiche e della Coagulazione, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Divisione di Ematologia, Viale Del Policlinico 155, 00161, Rome
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
S.C. Medicina Emostasi e Trombosi, Via Francesco Sforza 28, 20122, Milan
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Hematologie, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Instytut Hematologii I Transfuzjologii
Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych, Ul Indiry Gandhi 14, 02-776, Warsaw
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2025-06-04 | 2025-06-27 | |||
| France | 2025-08-08 | 2025-12-05 | |||
| Germany | 2025-06-18 | 2025-06-30 | |||
| Italy | 2025-07-17 | 2025-09-03 | |||
| Netherlands | 2025-08-22 | 2026-01-08 | |||
| Poland | 2025-08-18 | 2025-09-10 | |||
| Spain | 2025-06-26 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 107 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | d1_protocol-2024-515622-80-00-redacted | 2 |
| Protocol (for publication) | d4_patient-facing-documents_Redaction memo_ENG | 3 |
| Recruitment arrangements (for publication) | K1 recruitment procedure | 2.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed consent procedure_WP45338 | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 3.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and Informed Consent Procedure | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and Informed Consent Procedure | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_WP45338 | 2 |
| Recruitment arrangements (for publication) | K2_ Recruitment material companion ICF_adults-children_redacted | 1 |
| Recruitment arrangements (for publication) | K2_ Recruitment material companion ICF_adults-children_redacted | 2 |
| Recruitment arrangements (for publication) | K2_Document_additionnel_WP45338_REDACTED | 1 |
| Recruitment arrangements (for publication) | K2_WP45338_Adult-Child-companion guide | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF 12 tot 16 REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF IAF | 4 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF infant Authorization | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF main REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Main_REDACTED | 2 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Parent REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF PPA | 2 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Pregnant Partner | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF tot 12 REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_Appendix 1 data privacy parents | 2.0 |
| Subject information and informed consent form (for publication) | L1_Appendix 1 data privacy patient | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF Adult Patients_redacted | 3 |
| Subject information and informed consent form (for publication) | L1_ICF Parents_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_ICF_12-16 year_redacted | 3 |
| Subject information and informed consent form (for publication) | L1_ICF_3-6 year | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_7-11 year_redacted | 3 |
| Subject information and informed consent form (for publication) | L1_Privacy consent form other subjects | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 12-17 yr_redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 12-17 yr_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 3-6 yr | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 7-11 years_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 7-11 yr_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 12 to 17 years_EN_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 12 to 17 years_FR_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 12 to 17 years_NL_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 3 to 6 years_EN | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 3 to 6 years_FR | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 3 to 6 years_NL | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 7 to 11 years_EN_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 7 to 11 years_FR_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent Form Ages 7 to 11 years_NL_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF IAF | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Infant and Privacy sheet | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Infant Authorization Form_EN | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Infant Authorization Form_FR | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Infant Authorization Form_NL | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF main adults-parents_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main ICF_EN_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main ICF_FR_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main ICF_NL_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA_EN | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA_FR | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PPA_NL | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnant partner and Privacy sheet | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 1 Risks_Adult_Clean | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 1 Risks_ages 15-17_Clean | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 1 Risks_Caregiver_Clean | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 2 GDPR_Adult_Clean | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Caregiver_REDACTED | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Enfant-ne_WP45338_CLEAN | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_IAF_Clean | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_adult_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_ages 15-17_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_ages 3-6_Clean | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_ages 7-14_REDACTED | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Partenaire-enceinte_WP45338_CLEAN | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_PPA_Clean | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Principal_Adulte_WP45338_REDACTED | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Principal_Aidant_WP45338_REDACTED | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_principal_Enfants_12-17_WP45338_REDACTED | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_principal_Enfants_3-6_WP45338_CLEAN | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_principal_Enfants_7-11_WP45338_REDACTED | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Principal_Parents_WP45338_REDACTED | 2 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Guide_adultes-enfants_WP45338_REDACTED | 1 |
| Subject information and informed consent form (for publication) | L2_Other Subject Information Material_ICF Companion Guidelines_REDACTED | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Recruitment and Informed consent procedure_WP45338 | 2 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Sac-Isotherme | 1 |
| Subject information and informed consent form (for publication) | L2_Sponsor Statement On Use Of ICF | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-elocta | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-fanhdi | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-fanhdi-2024-515622-80-00 | NA |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-FEIBA | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-feiba-2024-515622-80-00 | NA |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-haemate-p | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-Haemate-P b-2024-515622-80-00 | NA |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-NovoSeven | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-novoseven.pdf | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-veyvondi | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-voncento | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-wilate-2024-515622-80-00 | NA |
| Summary of Product Characteristics (SmPC) (for publication) | e2_smpc-willfact | N/A |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_BE-DE-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_ENG-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_ES-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_FR-BE-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_FR-FR-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_IT-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_NL-BE-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_NL-NL-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_PL-2024-515622-80-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_SE-SE-2024-515622-80-00 | 2 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-16 | Belgium | Acceptable with conditions 2025-05-05
|
2025-05-05 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-05-22 | Belgium | Acceptable with conditions 2025-05-05
|
2025-05-22 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-06-11 | Belgium | Acceptable with conditions 2025-05-05
|
2025-06-11 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-06-27 | Belgium | Acceptable with conditions 2025-05-05
|
2025-06-27 |
| 5 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-10-23 | Belgium | Acceptable 2026-02-02
|
2026-02-03 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2026-02-20 | Acceptable 2026-02-02
|
2026-02-20 | |
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-6 | 2026-03-11 | Belgium | Acceptable 2026-02-02
|
2026-03-11 |