Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
50
Countries
6
Sites
11
Haemophilia A
The primary objective of this study is to evaluate the overall perioperative haemostatic efficacy of Nuwiq, in combination with ongoing emicizumab prophylaxis, in patients with severe haemophilia A undergoing major surgery.
Key facts
- Sponsor
- Octapharma AG
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 19 Oct 2023 → ongoing
- Decision date (initial)
- 2023-09-11
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- Octapharma AG
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Prophylaxis, Efficacy
The primary objective of this study is to evaluate the overall perioperative haemostatic efficacy of Nuwiq, in combination with ongoing emicizumab prophylaxis, in patients with severe haemophilia A undergoing major surgery.
Secondary objectives 5
- To evaluate intra- and post-operative surgical haemostatic efficacy of Nuwiq, in combination with emicizumab prophylaxis.
- To evaluate perioperative coagulation factor VIII (FVIII) plasma levels in patients receiving Nuwiq in combination with emicizumab prophylaxis.
- To evaluate perioperative thrombin generation (TG) in patients receiving Nuwiq in combination with emicizumab prophylaxis.
- To evaluate perioperative efficacy of Nuwiq, in combination with emicizumab prophylaxis, assessed by the criteria recommended by the World Federation of Hemophilia (WFH).
- To evaluate perioperative safety of Nuwiq in combination with emicizumab prophylaxis.
Conditions and MedDRA coding
Haemophilia A
Regulatory references
- EMA paediatric investigation plan (PIP)
- EMEA-001024-PIP01-10
- Plan to share IPD
- No
- IPD plan description
- N/A
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Severe haemophilia A (FVIII activity [FVIII:C] <1%) according to medical history.
- Male patients at least 12 years of age.
- Previous treatment with any FVIII product(s) for at least 150 exposure days.
- On regular prophylaxis with emicizumab for at least 3 months prior to a scheduled major elective surgery requiring FVIII treatment.
- Freely given written informed consent.
Exclusion criteria 7
- Coagulation disorder other than haemophilia A.
- Present or past FVIII inhibitor (≥0.6 Bethesda units [BU]/mL) according to medical history.
- Severe liver or kidney disease (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] levels >5 times the upper limit of normal; or creatinine >120 μmol/L).
- Current participation in another interventional clinical trial.
- Treatment with any investigational product within 30 days prior to screening visit.
- Known hypersensitivity to Nuwiq’s active substance or its excipients (sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium citrate dihydrate, poloxamer 188)
- Already had surgery in this study
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is the overall haemostatic efficacy (“success” or “failure”) of Nuwiq in severe haemophilia A patients receiving emicizumab prophylaxis and undergoing major surgery.
Secondary endpoints 9
- Assessment of intraoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale.
- Assessment of postoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale.
- Perioperative FVIII plasma levels immediately before (≤30 minutes) and after (15-30 minutes) Nuwiq injections.
- Perioperative haemostatic efficacy assessed using the 4-point scale recommended by the WFH.
- Incidence of adverse events (AEs).
- Incidence of thrombotic events.
- Incidence of FVIII inhibitor formation.
- Number of allogeneic blood products (red blood cells, platelets, and other blood products) transfused
- Perioperative TG immediately before (≤30 minutes) and after (15-30 minutes) Nuwiq injections
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 8
Nuwiq 1500 IU powder and solvent for solution for injection
PRD9437977 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/008
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nuwiq 2500 IU powder and solvent for solution for injection
PRD5992277 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/005
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nuwiq 4000 IU powder and solvent for solution for injection
PRD5992275 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/007
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nuwiq 3000 IU powder and solvent for solution for injection
PRD5992276 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/006
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nuwiq 2000 IU powder and solvent for solution for injection
PRD1696360 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/004
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nuwiq 250 IU powder and solvent for solution for injection
PRD1696357 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/001
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nuwiq 500 IU powder and solvent for solution for injection
PRD1696358 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/002
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nuwiq 1000 IU powder and solvent for solution for injection
PRD1696359 · Product
- Active substance
- Simoctocog Alfa
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 0 IU international unit(s)
- Max total dose
- 0 IU international unit(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BD02 — COAGULATION FACTOR VIII
- Marketing authorisation
- EU/1/14/936/003
- MA holder
- OCTAPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Octapharma AG
- Sponsor organisation
- Octapharma AG
- Address
- Seidenstrasse 2
- City
- Lachen Sz
- Postcode
- 8853
- Country
- Switzerland
Scientific contact point
- Organisation
- Octapharma AG
- Contact name
- Sigurd Knaub, SVP CRD Haematology
Public contact point
- Organisation
- Octapharma AG
- Contact name
- Sigurd Knaub, SVP CRD Haematology
Locations
6 EU/EEA countries · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Croatia | Ongoing, recruiting | 2 | 1 |
| Finland | Authorised, recruiting | 28 | 1 |
| France | Ongoing, recruiting | 3 | 2 |
| Germany | Ongoing, recruiting | 5 | 2 |
| Italy | Ongoing, recruiting | 4 | 3 |
| Spain | Ongoing, recruiting | 3 | 2 |
| Rest of world
United States, United Kingdom
|
— | 5 | — |
Investigational sites
University Hospital Centre Zagreb
Hematology Department, Ulica Mije Kispatica 12, Zagreb, Grad Zagreb
HUS-Yhtymae
Coagulation disorders Unit, Department of Hematology, Haartmaninkatu 4, 00290, Helsinki
Centre Hospitalier Regional Universitaire De Tours
Service : Hématologie - Hémostase, 2 Boulevard Tonnelle, 37000, Tours
Centre Hospitalier Universitaire De Nantes
Centre d'hémostase clinique, 1 Place Alexis Ricordeau, 44000, Nantes
University Medical Center Hamburg-Eppendorf
II. Medizinische Klinik und Poliklinik, Martinistrasse 52, Eppendorf, Hamburg
Vivantes Netzwerk fuer Gesundheit GmbH
Klinik fuer Angiologie/Haemastaseologie, Landsberger Allee 49, Friedrichshain, Berlin
Careggi University Hospital
Centro Emofilia, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Azienda Ospedaliera Pugliese Ciaccio
Emato-Oncologico, UO Emostasi e Trombosi, Via Vinicio Cortese 25, 88100, Catanzaro
Humanitas Research Hospital
Thrombosis and Haemorrhagic Diseases Center, Via Alessandro Manzoni 56, 20089, Rozzano
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 |
|---|---|---|---|---|---|
| Croatia | 2023-11-29 | 2025-02-15 | |||
| Finland | 2024-05-17 | ||||
| France | 2024-03-25 | 2025-02-26 | |||
| Germany | 2024-04-12 | 2025-08-14 | |||
| Italy | 2023-12-18 | 2025-09-09 | |||
| Spain | 2023-10-19 | 2025-09-09 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | K1_2022-502060-21-00_ES_Recruitment arrangements_Sanitized | 1 |
| Recruitment arrangements (for publication) | K1_2022-502060-21-00_ITA_Recruitment arrangements_Sanitized | 1 |
| Recruitment arrangements (for publication) | K1_DE_Recrutiment arrangements_Redacted | 1 |
| Recruitment arrangements (for publication) | K1_FI_Recruitment and Informed consent procedure_Redacted | 1 |
| Subject information and informed consent form (for publication) | L1_2022-502060-21-00_ES_SIS and ICF for 12-17 years_Sanitized | 3.0 |
| Subject information and informed consent form (for publication) | L1_2022-502060-21-00_ES_SIS and ICF for Adult_Sanitized | 3.0 |
| Subject information and informed consent form (for publication) | L1_2022-502060-21-00_ES_SIS and ICF for Parents-Guardians_Sanitized | 3.0 |
| Subject information and informed consent form (for publication) | L1_2022-502060-21-00_ITA_ICF_ Parents EU Italy ICF 16 May 2023_Sanitized | 2.0 |
| Subject information and informed consent form (for publication) | L1_2022-502060-21-00_ITA_ICF_Adult Patient Italy ICF_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_2022-502060-21-00_ITA_ICF_Italy Assent for adolescents 12-17 years 16 May 2023_Sanitized | 2.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS and ICF Adolescents 12-16 yr_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS and ICF Adults_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS and ICF Parents_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS and ICF_Adolescents 12-16 yr_TC_redacted | 3 |
| Subject information and informed consent form (for publication) | L1_FIN-FIN ICF Adult_Sanitized | 6.0 |
Application history
10 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-01-31 | Germany | Acceptable 2023-05-19
|
2023-08-15 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-10-03 | Acceptable | 2023-11-17 | |
| 3 | SUBSEQUENT ADDITION OF MSC | APP-3 | 2023-11-24 | Acceptable 2023-05-19
|
2024-02-27 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-05-10 | Germany | Acceptable 2024-07-15
|
2024-07-16 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-06-25 | Germany | Acceptable | 2025-07-11 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-06-25 | Acceptable | 2025-08-01 | |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-06-25 | Acceptable | 2025-09-25 | |
| 8 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-06-25 | Acceptable | 2025-07-29 | |
| 9 | SUBSTANTIAL MODIFICATION | SM-8 | 2025-08-22 | Germany | Acceptable | 2025-09-04 |
| 10 | SUBSTANTIAL MODIFICATION | SM-9 | 2025-08-22 | Acceptable | 2025-09-17 |