Marstacimab for Hemophilia

Recruiting at 53 trial locations

Overseen By Pfizer CT.gov Call Center

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Marstacimab

Must not be taking: Immunomodulatory drugs

Disqualifiers: Coronary artery disease, Thrombosis, Ischemic disease, Abnormal renal function, Unstable hepatic function, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 7 years

245 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications like immunomodulatory drugs (e.g., IVIG, routine systemic corticosteroids, rituximab) and FVIII or FIX replacement during the study. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the drug Marstacimab for treating hemophilia?

Research shows that Marstacimab, a drug targeting a protein involved in blood clotting, effectively reduces bleeding episodes in patients with severe hemophilia A and B. In a long-term study, participants experienced fewer bleeding events, and the drug was well-tolerated with no serious side effects. ^{1 2 3 4 5}

How is the drug Marstacimab different from other hemophilia treatments?

Marstacimab is unique because it is a human monoclonal antibody that targets and inhibits the tissue factor pathway inhibitor (TFPI), which is different from traditional treatments that replace missing clotting factors. It is designed as a prophylactic treatment to prevent bleeding episodes in patients with hemophilia A and B, and is administered as a weekly subcutaneous injection. ^{1 2 3 4 5}

What is the purpose of this trial?

Study B7841007 is an open-label extension study to assess the long-term safety, tolerability, and efficacy of prophylaxis treatment with marstacimab in participants who did not require "Early Termination" from the Phase 3 Study B7841005 and from the Phase 3 Study B7841008. Study B7841005: approximately 145 adolescent and adult participants 12 to \<75 years of age with severe hemophilia A or moderately severe to severe hemophilia B (defined as FVIII activity \<1% or FIX activity ≤2%, respectively) with or without inhibitors are expected to be enrolled in Study B7841005 during which they will receive prophylaxis (defined as treatment by SC injection of marstacimab). Study B7841008: this is an ongoing Phase 3, open-label study in pediatric participants \<18 years of age with severe hemophilia A (FVIII Coagulation Factor Activity \<1%) or moderately severe to severe hemophilia B (FIX Coagulation Factor Activity ≤2%). A sequential approach will be used in enrolling at least 100 pediatric participants, at least 20 of which will be aged ≥12 to \<18 years and at least 80 participants will be aged ≥1 to \<12 years. At the start of study B7841008, the dosing and data available in adolescent and adult participants in Study B7841005 supported the initiation of B7841008 study in participants aged ≥12 to \<18 years. Subsequently, additional safety and efficacy data from adolescent participants in Study B7841005 became available for benefit/risk assessment in support of dosing participants aged ≥6 to \<12 years. Based on the positive benefit/risk assessment conducted by both internal Pfizer review and eDMC review, dosing of the ≥6 to \<12 years age group was initiated in June 2023 in B7841008 Study. Data from participants ≥6 years from B7841008 Study and Study B7841005 will support the dosing of participants aged ≥1 to \<6 years. All participants will be provided the prefilled pen (PFP) for administration of marstacimab in the study. Use of the prefilled syringe (PFS) will be permitted at the investigator's discretion for those participants who have difficulty with administration of the PFP. Additionally, participants will be provided the PFS for use in this study in countries where the PFS is anticipated to be the only presentation available commercially. An optional, open-label, single arm, substudy using the PFP was completed in the first 23 participants rolled over from Study B7841005 who agreed to participate in the substudy.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adolescents and adults aged 12 to <75 with severe hemophilia A or B, weighing at least 35 kg, who completed a prior study without early termination. It's not for those planning surgery, with unstable HIV or liver function, abnormal kidney function, using certain immune treatments, or having a history of significant heart or blood vessel problems.

Inclusion Criteria

Participants have successfully completed participation in study B7841005, defined as did not require "Early Termination" from study B7841005

I weigh at least 35 kg.

Exclusion Criteria

I am currently using or plan to use immune tolerance therapy for my condition.

You cannot participate in this study if you have recently participated in another research study involving experimental drugs or vaccines within the last 30 days or during this study. However, there is an exception if you participated in a study called B7841005.

I am on regular treatment with drugs that affect my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive prophylaxis treatment with marstacimab via subcutaneous injection

Up to 7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Long-term safety, tolerability, and efficacy of marstacimab prophylaxis are assessed

Long-term

Treatment Details

Interventions

• Marstacimab

Trial Overview The trial tests marstacimab (PF-06741086), given as a weekly subcutaneous injection to prevent bleeding in hemophilia patients. Participants from an earlier phase will continue treatment to assess long-term safety and effectiveness. An optional substudy uses a pre-filled pen for administration.

Participant Groups

Group I: PF-06741086 Experimental Treatment 1 Intervention

For participants aged ≥12 years 300 milligrams(mg) subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria. For participants aged ≥6 to \<12 years is marstacimab 150 mg SC for initial loading dose followed by 75 mg SC QW. 150 mg sc qw is prescribed for participants who meet dose escalation criteria.

Marstacimab is already approved in United States, European Union for the following indications:

Approved in United States as Hympavzi for:

• Hemophilia A
• Hemophilia B

Approved in European Union as Hympavzi for:

• Hemophilia A
• Hemophilia B

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Marstacimab, a monoclonal antibody, effectively enhances hemostasis in hemophilia A and B by increasing thrombin generation without causing excessive levels, making it a promising prophylactic treatment.

In a mouse model, marstacimab combined with activated prothrombin complex concentrate (aPCC) significantly reduced bleeding by 83.3%, indicating its potential effectiveness in preventing bleeding episodes in hemophilia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemostatic efficacy of marstacimab alone or in combination with bypassing agents in hemophilia plasmas and a mouse bleeding model. Pittman, DD., Rakhe, S., Bowley, SR., et al.[2023]

In a study involving 18 patients with rare bleeding disorders, Marstacimab showed potential to improve thrombin generation in plasma samples, indicating it may help restore blood clotting balance.

While Marstacimab improved key thrombin generation metrics (lag time, peak, and ETP), none of the values reached normal levels, suggesting further research is needed to assess its clinical effectiveness in treating these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-TFPI for hemostasis induction in patients with rare bleeding disorders, an ex vivo thrombin generation (TG) guided pilot study. Barg, AA., Brutman-Barazani, T., Avishai, E., et al.[2022]

Marstacimab, a monoclonal antibody, was found to be safe and effective in preventing bleeding episodes in patients with severe hemophilia A and B during a long-term study of up to 365 days involving 20 participants.

The treatment was well tolerated, with no serious adverse events or thrombotic events reported, and it maintained a low annualized bleeding rate, demonstrating comparable efficacy to previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of the anti-tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results. Mahlangu, J., Luis Lamas, J., Cristobal Morales, J., et al.[2023]

In a three-month study involving 26 participants with hemophilia A or B, marstacimab, a monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), was found to be safe and well tolerated, with 80.8% of participants experiencing treatment-emergent adverse events (TEAEs).

Marstacimab significantly reduced annualized bleeding rates (ABRs) compared to both an external control group and pretreatment rates, demonstrating its efficacy in managing bleeding episodes in hemophilia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b/2 clinical study of marstacimab, targeting human tissue factor pathway inhibitor, in haemophilia. Mahlangu, JN., Lamas, JL., Morales, JC., et al.[2023]

Marstacimab is a promising investigational treatment for severe hemophilia A or B that works by neutralizing tissue factor pathway inhibitor (TFPI), potentially increasing the effectiveness of the coagulation pathway to prevent bleeding episodes.

Three validated electrochemiluminescence-based methods have been developed to detect antidrug antibodies (ADAs) against marstacimab, which is crucial for assessing the safety and efficacy of the treatment in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of Antidrug Antibody Assays During the Development of Anti-Tissue Factor Pathway Inhibitor Monoclonal Antibody Marstacimab. Donley, J., Jani, D., Zhu, T., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Hemostatic efficacy of marstacimab alone or in combination with bypassing agents in hemophilia plasmas and a mouse bleeding model. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Anti-TFPI for hemostasis induction in patients with rare bleeding disorders, an ex vivo thrombin generation (TG) guided pilot study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of the anti-tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A phase 1b/2 clinical study of marstacimab, targeting human tissue factor pathway inhibitor, in haemophilia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Evolution of Antidrug Antibody Assays During the Development of Anti-Tissue Factor Pathway Inhibitor Monoclonal Antibody Marstacimab. [2023]