Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Pediatric, Patients

Age range

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

Gender

Male

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

14 Nov 2022 → ongoing

Decision date (initial)

2025-02-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2022-500470-33-00

ClinicalTrials.gov

NCT05145127

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine the safety and tolerability of long-term treatment with marstacimab in severe hemophilia A or moderately severe to severe hemophilia B (FVIII activity <1% or FIX activity ≤2%, respectively) participants 1 to <75 years of age with or without inhibitors.

Secondary objectives 2

1. To evaluate long-term efficacy of treatment with marstacimab in severe haemophilia A or moderately severe to severe hemophilia B (FVIII activity <1% or FIX activity ≤2%, respectively) participants 1 to <75 years of age with or without inhibitors.
2. To evaluate the effect of marstacimab on HRQoL

Conditions and MedDRA coding

Haemophilia

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002285-PIP02-19

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participants continuing from Study B7841005 and from Study B7841008 have met age criteria in their respective studies.
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures
3. All participants continuing from Study B7841005 and from Study B7841008 will have met minimum weight criteria in their respective study.
4. The investigator, or a person designated by the investigator, will obtain written/electronically signed informed consent and assent from each study participant or participant’s legal guardian//legally designated representative and the participant’s assent, when applicable, before any study-specific activity is performed. All legal guardians/legally designated representative should be fully informed, and participants should be informed to the fullest extent possible, about the study in language and terms they are able to understand. The investigator will retain the original copy of each participant's signed consent/assent document.
5. Participants who successfully completed participation in Studies B7841005 or B7841008, defined as did not require “Early Termination” from Studies or B7841008, respectively.

Exclusion criteria 8

1. Previous or current treatment for or history of coronary artery disease, venous or arterial thrombosis (CTCAE Grade >3), or ischemic disease (except catheter associated thrombosis).
2. Abnormal renal function as defined by eGFR <30 mL/min/1.73 m2 (see Section 10.2.1 of the protocol for formulas used in eGFR calculation). Prior determinations of eGFR up to 90 days prior to TPY1 Day 1 visit may be used to determine eligibility
3. Known planned surgical procedure during the planned study period. Potential participants who have a surgical procedure planned during the study period may be eligible for participation on a case-by-case basis, only after consultation between the investigator and the Pfizer medical monitor
4. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgement, make the participant inappropriate for the study. Unstable hepatic function as determined by the investigator clinical assessment and review of the participant’s most recent laboratory results, which would make the participant inappropriate for the study. • For participants known to be HIV+, worsening disease status as determined by the investigator clinical assessment and review of the participant’s most recent laboratory results, to include recent locally available CD4 count (if available), which would make the participant inappropriate for the study.
5. Regular, concomitant therapy with immunomodulatory drugs (eg, IVIG, and routine systemic corticosteroids, rituximab).
6. Ongoing or planned use of immune tolerance induction or prophylaxis with FVIII or FIX replacement during the study.
7. Participation in other studies involving investigational drug(s) or investigational vaccine(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry or during study participation, with the exception of participation in Studies B7841005 and B7841008.
8. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 9

1. Safety Endpoints •AEs and SAEs
2. Incidence and severity of thrombotic events.
3. Incidence and severity of thrombotic microangiopathy.
4. Disseminated intravascular coagulation/consumption coagulopathy.
5. Immunogenicity (incidence of ADA and clinically significantly persistent NAb against marstacimab).
6. Incidence and severity of injection site reaction.
7. Changes in vital signs.
8. Incidence of clinically significant laboratory value abnormalities.
9. Incidence of severe hypersensitivity and anaphylactic reactions.

Secondary endpoints 12

1. The following efficacy endpoints will be reported for each year of participation (Year 1, Year 2, etc): •Annualized rate of treated bleeding episodes.
2. Incidence of joint bleeds.
3. Incidence of spontaneous bleeds.
4. Incidence of target joint bleeds
5. Incidence of total bleeds (treated and untreated).
6. Change in joints as measured by the HJHS for participants ≥4 years of age.
7. Number of target joints
8. Haem-A-QoL (≥17 years of age)/Haemo-QoL (age-dependent versions 12 to <17 years of age and 8 to <12 years of age).
9. Health Utilities Measure (EQ-5D-5L) for participants ≥12 years of age.
10. Total coagulation factor or bypass product consumption.
11. Health Utilities Measure (EQ-5D-Y) Self Assessment for participants ≥7 to ≤11 years of age
12. Health Utilities Measure (EQ-5D-Y) Proxy Assessment for participants ≥4 to ≤ 6 years of age

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 10

Locations

9 EU/EEA countries · 21 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 215 files

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

Application history

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