Nuwiq Dosing and outcomes In the ManagEment of women/girls with haemophilia A Needing FVIII treatment for Surgery – an International, Open-label, Non-controlled study (NuDIMENSION)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Octapharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

15 Dec 2023 → ongoing

Decision date (initial)

2023-08-21

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Octapharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis

To evaluate the overall perioperative haemostatic efficacy of Nuwiq in women/girls with haemophilia A undergoing major surgery.

Secondary objectives 5

1. Intra- and post-operative surgical haemostatic efficacy of Nuwiq
2. Perioperative coagulation factor FVIII (FVIII) plasma levels
3. Perioperative efficacy of Nuwiq assessed by the criteria recommended by the World Federation of Hemophilia (WFH)
4. Perioperative safety of Nuwiq
5. Perioperative use of allogeneic blood products (red blood cells, platelets, and other blood products)

Conditions and MedDRA coding

Haemophilia A

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001024-PIP01-10

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Women/girls with moderate or mild haemophilia A (FVIII activity [FVIII:C] ≥1 - <40%) according to medical history
2. At least 12 years of age
3. Scheduled to undergo major elective surgery* requiring FVIII treatment, including elective and emergency procedures and caesarean section in pregnant women with haemophilia A Note: - Pregnant participants may be included regardless of current FVIII activity levels, acknowledging physiological increases during pregnancy; Inclusion is permitted if, in the opinion of the Investigator, the participant is expected to require FVIII treatment before and during the immediate postpartum period (for a minimum of 3 days following deliverycaesarean section). Participants undergoing eEmergency surgeries may be included if the Investigator confirms that all protocol requirements are can be met, including timely informed consent (ICF) and adherence to the sampling schedule.
4. Freely given written informed consent of the participant, or parent/legal representative where applicable, obtained in accordance with local regulations
5. Additionally, women/girls with documented FVIII activity levels between ≥>40% and 50% may be included if the following criteria are met: There is a documented history of clinically significant bleeding episodes consistent with haemophilia A; and/or There is either documented prior treatment with FVIII concentrates or a clear clinical indication that FVIII treatment would have been appropriate (e.g., use of FVIII from a family member, or treatment with alternative haemostatic agents due to access limitations);
6. Note: Participants with transiently elevated FVIII levels due to physiological or pathological conditions (e.g., inflammation, pregnancy, malignancy) may still be eligible if historical data supports a diagnosis of haemophilia A.

Exclusion criteria 8

1. Coagulation disorder other than haemophilia A
2. Present or past FVIII inhibitors (≥0.6 Bethesda units [BU]/mL)
3. 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)
4. Pregnancy (except in participants with a planned caesarean section)
5. Current participation in another interventional clinical trial
6. Treatment with any investigational medicinal product (IMP) within 30 days prior to screening visit
7. Known hypersensitivity to Nuwiq’s active substance or its excipients (sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium citrate dihydrate, poloxamer 188)
8. Already had surgery in this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The overall haemostatic efficacy of Nuwiq in women/girls with haemophilia A undergoing major surgery assessed at the end of surgery by the surgeon and at the end of the POP by the investigator. Overall haemostatic efficacy will be adjudicated by the IDMC, using a pre-defined algorithm. The end of the POP for a surgical event will be defined as completion of wound healing, as defined by the investigator. Subsequent dosing of Nuwiq, if necessary, will not included in the assessment of efficacy

Secondary endpoints 8

1. Assessment of intraoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale
2. Assessment of postoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale
3. Perioperative FVIII plasma levels immediately before (≤30 minutes) and after (15-30 minutes) Nuwiq injections
4. Perioperative haemostatic efficacy assessed using the 4-point scale recommended by the WFH (1)
5. Incidence of adverse events (AEs)
6. Incidence of thrombotic events
7. Incidence of FVIII inhibitor formation
8. The number of allogeneic blood products (red blood cells, platelets, and other blood products) transfused

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

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, PhD, SVP CRD Haematology

Public contact point

Organisation

Octapharma AG

Contact name

Sigurd Knaub, PhD, SVP CRD Haematology

Locations

6 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications