Marstacimab for Hemophilia

(BASIS KIDS Trial)

Recruiting at 78 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Factor VIII, Factor IX

Must not be taking: Emicizumab, Fitusiran

Disqualifiers: Coronary artery, Thrombotic, Ischemic, 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: 12

Duration: 12 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effects of marstacimab, a new treatment for children with hemophilia, a condition causing frequent bleeding due to poor blood clotting. The goal is to determine if marstacimab, administered as a weekly under-the-skin shot, can prevent these bleeding episodes. Children who may qualify have severe forms of hemophilia A or B and have maintained detailed records of their treatment and bleeding events for at least a year. Participants will compare their experiences on marstacimab to their previous treatment, aiding researchers in assessing its effectiveness. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for hemophilia.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain medications like systemic antifibrinolytics, medications that may increase the risk of bleeding, and some non-steroidal anti-inflammatory drugs within 120 hours of the first dose and while on the study. Also, ongoing or planned use of ITI, or prophylaxis with FVIII or FIX replacement after starting the study intervention is not allowed. Please discuss your current medications with the study team to ensure they are permitted.

Is there any evidence suggesting that marstacimab is likely to be safe for pediatric patients with hemophilia?

Research has shown that marstacimab is generally well-tolerated in adults with severe hemophilia. Most adults in previous studies did not experience serious side effects, though some had mild reactions at the injection site.

The FDA has approved marstacimab for adults to prevent bleeding episodes, indicating it has met safety standards for that age group. While this trial focuses on children, the adult data provides some reassurance about its safety.

This is a Phase 3 trial, indicating researchers' confidence in its safety based on earlier studies. However, more information from this trial is needed to confirm its safety for children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hemophilia?

Marstacimab is unique because it offers a new approach for treating hemophilia through weekly subcutaneous injections. Unlike traditional treatments that often require frequent intravenous infusions, marstacimab targets tissue factor pathway inhibitor (TFPI), a protein that regulates blood clotting. This mechanism of action is different from the standard use of factor replacement therapies, which focus on replacing the missing or deficient clotting factors. Researchers are excited about marstacimab because its convenient administration and novel action could improve patient quality of life and potentially enhance treatment efficacy.

What evidence suggests that marstacimab might be an effective treatment for hemophilia?

Research has shown that marstacimab, which participants in this trial will receive, helps treat hemophilia by reducing bleeding episodes. In studies, marstacimab significantly lowered the annual number of bleeding incidents for patients with hemophilia A and B. This treatment is a monoclonal antibody that blocks a protein interfering with normal blood clotting, aiding the body in stopping bleeding more effectively. Even patients with inhibitors—antibodies that prevent standard treatments from working—experienced fewer bleeding episodes with marstacimab. Overall, marstacimab has demonstrated promising results for safety and effectiveness in managing hemophilia. ^{1 3 6 7 8}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for boys with severe Hemophilia A or moderately to severe Hemophilia B, ages 1-17. They must have a history of consistent treatment and bleed documentation for at least a year, weigh enough (specifics vary by age), and not be on certain other treatments like gene therapy or non-factor replacement therapies.

Inclusion Criteria

I have been diagnosed with severe hemophilia A or moderate to severe hemophilia B.

I am a man of the right age and weight for the study.

I am aged 6 to 11 and weigh at least 19 kg.

Exclusion Criteria

Abnormal hematology, renal or hepatic function laboratory results at screening

Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members

I have a surgery scheduled during the study period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive weekly subcutaneous injections of marstacimab for 12 months

12 months

10 visits (in-person), 2 visits (home), 6 calls (telephone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Marstacimab

Trial Overview The study tests marstacimab's safety and effectiveness in preventing bleeding episodes in pediatric hemophilia patients. Participants will receive weekly subcutaneous shots of marstacimab over a 12-month period, with their experiences compared to historical data from when they weren't taking the medicine.

How Is the Trial Designed?

Group I: marstacimab (PF-06741086) Experimental Treatment 1 Intervention

Weekly subcutaneous injections.

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

Published Research Related to This Trial

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]

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]

HLA-A*31:01 is strongly associated with carbamazepine-induced DRESS in both European and Chinese populations, indicating it could be a useful genetic marker for predicting this severe reaction in patients taking carbamazepine.

In contrast, HLA-B*15:02 is linked to carbamazepine-induced SJS/TEN specifically in Chinese patients, highlighting the need for further research into genetic factors influencing these reactions in different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis. Genin, E., Chen, DP., Hung, SI., et al.[2022]

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 of 119 multiple sclerosis patients, those with the HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly more likely to experience anaphylactic reactions to natalizumab, indicating a strong genetic risk factor for these severe allergic responses.

Conversely, the presence of the HLA-DRB1*15 allele was associated with a lower risk of anaphylactic reactions, suggesting that HLA-DRB1 genotyping could be a useful tool for identifying patients at risk for serious hypersensitivity reactions before starting natalizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles. de la Hera, B., Urcelay, E., Brassat, D., et al.[2018]

HLA-A*31:01 is a significant genetic risk factor for both serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI) caused by carbamazepine, with odds ratios indicating a strong association in European populations.

The study identified that the hypersensitivity syndrome is particularly linked to HLA-A*31:01, while a different genetic marker, HLA-B*57:01, is associated with more severe cases like Stevens-Johnson syndrome, highlighting the importance of genetic testing in predicting adverse reactions to carbamazepine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions. Nicoletti, P., Barrett, S., McEvoy, L., et al.[2021]

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]

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]

A scoping review of 149 studies found that certain HLA alleles, particularly HLA-B*15:02, are associated with idiosyncratic adverse drug reactions (ADRs) to medications like carbamazepine, suggesting that HLA-typing could help prevent these reactions in susceptible individuals.

The studies reviewed were highly heterogeneous, making direct comparisons difficult, highlighting the need for standardized definitions and reporting methods in future research to better understand HLA-associated ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-associated adverse drug reactions - scoping review. Jeiziner, C., Wernli, U., Suter, K., et al.[2023]

Oxcarbazepine, a common treatment for focal epilepsy, can cause serious hypersensitivity reactions, similar to other antiepileptic drugs, but routine genetic screening for the HLA-B*15:02 allele, which increases risk, is not currently recommended before its use.

A case study of a pediatric patient who developed severe drug reactions after taking oxcarbazepine highlights the need for increased awareness and potential implementation of preemptive pharmacogenomic testing to prevent such adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-A*31:01 and Oxcarbazepine-Induced DRESS in a Patient With Seizures and Complete DCX Deletion. Kim, H., Chadwick, L., Alzaidi, Y., et al.[2021]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-phase-3-results

Pfizer Announces Positive Topline Phase 3 Results for ... Study demonstrates superiority, showing both statistically significant and clinically meaningful reduction in annualized bleeding rate with ...

2. ashpublications.org ashpublications.org/blood/article/146/14/1654/546041/Marstacimab-prophylaxis-in-hemophilia-A-B-without

Marstacimab prophylaxis in hemophilia A/B without inhibitors Key PointsMarstacimab, a monoclonal antibody, targets the tissue factor pathway inhibitor to rebalance hemostasis.Marstacimab reduced bleeding events and w.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12205756/

Marstacimab for the Treatment of Hemophilia A or B - PMC Although marstacimab appears to have a favorable safety and efficacy profile, the potential for immunogenicity remains a critical consideration, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03938792

NCT03938792 | Study of the Efficacy and Safety PF ... Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial. Blood. 2025 Oct 2;146(14):1654-1663. doi: 10.1182/blood ...

5. hematologyadvisor.com hematologyadvisor.com/news/hemophilia-marstacimab-efficacy-inhibitors-treatment-risk/

Marstacimab Shows Efficacy in Hemophilia With Inhibitors Once-weekly subcutaneous marstacimab (Hympavzi™) significantly reduced bleeding episodes in patients with hemophilia A or B with inhibitors, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03938792

NCT03938792 | Study of the Efficacy and Safety PF ... Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial. Blood. 2025 Oct 2;146(14):1654-1663. doi: 10.1182/blood ...

7. bleeding.org bleeding.org/news/pfizer-announces-phase-3-trial-results-for-hemophiliainhibitor-therapy

Pfizer Announces Phase 3 Trial Results for Hemophilia ... HYMPAVZI™ (marstacimab-hncq) is FDA-approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40608864/

Marstacimab prophylaxis in hemophilia A/B without inhibitors Previous phase 1 and 2 trials established marstacimab safety and efficacy in adults with severe hemophilia A (HA) or B (HB). BASIS is an open- ...