Marstacimab for Hemophilia

(BASIS KIDS Trial)

Recruiting at 65 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

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called marstacimab) for the potential treatment of hemophilia in pediatric patients. This study will enroll pediatric participants from ages 1 to 17 years in a sequential manner. The study will open enrollment to adolescent participants aged 12 to 17 years first. Then children aged 6 to 11 years will be permitted to enroll. Lastly, children aged 1 to 5 years will be permitted to enroll. This study will enroll participants who: * have severe Hemophilia A or moderately severe to severe Hemophilia B (with or without inhibitors) * have accurate historical records documenting all factor VIII, factor IX, or bypass agent infusions and hemophilia bleed events for at least 1 year prior to entering the study * if a non-inhibitor patient, must be on a stable routine prophylaxis regimen with factor VIII or factor IX replacement products for at least 12 months prior to study entry * if an inhibitor patient, must be on an on-demand bypass treatment regimen during the 12 months prior to study entry All participants in this study will receive marstacimab to use prophylactically. Marstacimab will be given once a week as a subcutaneous (under the skin) shot. The first dose of marstacimab will be given at the study site by the study site staff. During the 12-month treatment period, weekly doses of marstacimab can be given at home, or if preferred, the doses may be given by the study site staff. To help us determine if the study medicine is safe and effective, we will compare participant experiences when they are taking the study medicine to a historical period when they were not. Researchers want to see if the study medicine works to prevent the bleeding episodes commonly experienced by patients with Hemophilia. Participants will be in this study for about 14 months (approximately 1 month in a Screening period, 12 months receiving treatment, and 1 month in a follow-up period) during which they will visit the study site at least 10 times. If preferred, and if local regulations allow it, 2 of the study visits can be completed at the participant's home instead of at the study site. There will also be 6 scheduled telephone calls approximately every 2 months.

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.

What data supports the idea that Marstacimab for Hemophilia is an effective treatment?

The available research shows that Marstacimab is effective in reducing bleeding episodes in patients with hemophilia. In a long-term study, participants who received weekly doses of Marstacimab had an average of 0 to 3.6 bleeding episodes per year, which is a significant reduction. Additionally, the treatment was well-tolerated, with no serious side effects reported. Compared to other treatments, Marstacimab offers a promising option for managing bleeding in hemophilia patients. ^{1 2 3 4 5}

What safety data is available for Marstacimab in treating Hemophilia?

The provided research does not contain any safety data related to Marstacimab, Hympavzi, PF-06741086, or marstacimab-hncq for Hemophilia. The studies focus on HLA-associated adverse drug reactions with other medications, such as natalizumab and carbamazepine, and do not mention Marstacimab or its related names. ^{6 7 8 9 10}

Is the drug Marstacimab a promising treatment for Hemophilia?

Yes, Marstacimab is a promising drug for treating Hemophilia. It is designed to prevent bleeding episodes in patients with Hemophilia A and B. Studies show that it can significantly reduce bleeding rates and is well-tolerated by patients, making it a potential long-term solution for managing the condition. ^{1 2 3 4 5}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

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]

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 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]

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]

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]

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]

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]

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

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles. [2018]

7. United States 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. [2022]

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

HLA-A*31:01 and Oxcarbazepine-Induced DRESS in a Patient With Seizures and Complete DCX Deletion. [2021]

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

Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions. [2021]

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

HLA-associated adverse drug reactions - scoping review. [2023]