SR604 for Hemophilia

Recruiting at 5 trial locations

Age: 18 - 65

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Equilibra Bioscience LLC

Disqualifiers: Thrombosis, Cardiac disease, Hypertension, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) of SR604 in healthy participants (Part A) and to evaluate the safety, tolerability, PK, PD, and efficacy of SR604 in participants with Hemophilia A or Hemophilia B, with or without inhibitors (Part B).

Will I have to stop taking my current medications?

The trial requires participants with Hemophilia A or B to undergo a weaning period from their current treatment or prophylaxis. This means you may need to gradually reduce or stop your current hemophilia medications before starting the study treatment.

What data supports the effectiveness of the drug SR604 for Hemophilia?

Research on hemophilia treatments shows that new therapies, like recombinant clotting factors with extended half-life, can improve treatment adherence and outcomes by allowing for less frequent dosing and maintaining higher levels in the blood. These advancements have led to better management of bleeding episodes and improved quality of life for patients. ^{1 2 3 4 5}

What safety data exists for treatments similar to SR604 for hemophilia?

The safety data for treatments similar to SR604, such as recombinant factor VIII products like REFACTO and Monoclate, show that while some patients experienced adverse events, these were generally not serious and similar to those seen with other treatments. Additionally, Premofil M SRK, another factor VIII concentrate, showed no side reactions or infections in patients during testing, indicating a good safety profile. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for individuals with severe Hemophilia A or B whose bleeding isn't controlled well by current treatments, and healthy subjects. Participants must have a BMI of 18-30 kg/m^2, weigh 50-90 kg, and have no significant medical issues. Men must use birth control during the study and for 90 days after.

Inclusion Criteria

Part B: Medical records documenting a minimum of 2 years of bleeding event history

My current treatment does not control my bleeding well.

My recent health checks, including heart and lab tests, show no significant issues.

Exclusion Criteria

Part A: Participants with a history of all types of thrombosis or related conditions

Part A: Participant has specific vital sign criteria at the screening visit

My family or I have a history of specific genetic conditions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Healthy participants receive single ascending doses of SR604 or placebo

8 weeks

Multiple visits for dose administration and monitoring

Treatment Part B

Participants with Hemophilia A or B receive multiple ascending doses of SR604

12 weeks

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• SR604 (Monoclonal Antibodies)

Trial Overview The study tests SR604's safety, how it's tolerated, its movement through and effects on the body (PK/PD) in healthy people (Part A), and those same factors plus effectiveness in those with severe Hemophilia A/B (Part B). Some will receive SR604; others a placebo.

Participant Groups

Group I: Part B: Cohort 4B (SR604 Dose 8) Experimental Treatment 1 Intervention

Participants with Hemophilia A or Hemophilia B will receive SR604 dose 8 as SC injection.

Group II: Part B: Cohort 3B (SR604 Dose 7) Experimental Treatment 1 Intervention

Participants with Hemophilia A or Hemophilia B will receive SR604 dose 7 as SC injection.

Group III: Part B: Cohort 2B (SR604 Dose 6) Experimental Treatment 1 Intervention

Participants with Hemophilia A or Hemophilia B will receive SR604 dose 6 as SC injection.

Group IV: Part B: Cohort 1B (SR604 Dose 5) Experimental Treatment 1 Intervention

Participants with Hemophilia A or Hemophilia B will receive SR604 dose 5 as SC injection.

Group V: Part A: Cohort 4A (SR604 Dose 4) Experimental Treatment 2 Interventions

Participants will receive single SC dose of SR604 dose 4 or matching placebo to SR604 on Day 1.

Group VI: Part A: Cohort 3A (SR604 Dose 3) Experimental Treatment 2 Interventions

Participants will receive single SC dose of SR604 dose 3 or matching placebo to SR604 on Day 1.

Group VII: Part A: Cohort 2A (SR604 Dose 2) Experimental Treatment 2 Interventions

Participants will receive single SC dose of SR604 dose 2 or matching placebo to SR604 on Day 1.

Group VIII: Part A: Cohort 1A (SR604 Dose 1) Experimental Treatment 2 Interventions

Participants will receive single subcutaneous (SC) dose of SR604 dose 1 or matching placebo to SR604 on Day 1.

Who Is Running the Clinical Trial?

Equilibra Bioscience LLC

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

Only 25 out of 2352 reviewed references on haemophilia outcomes were eligible for inclusion, indicating that it is still uncommon for registries to publish peer-reviewed research on treatment outcomes, particularly in Europe and North America.

The focus of existing research has been more on traditional outcomes like comorbidities and factor consumption, rather than on health-related quality of life or the social impacts of haemophilia, highlighting a gap in understanding the full effects of the disorder on patients' lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Registry-based outcome assessment in haemophilia: a scoping study to explore the available evidence. Osooli, M., Berntorp, E.[2022]

The GOAL-Hēm tool was refined based on feedback from 38 participants (19 adults with hemophilia and 19 caregivers), resulting in significant changes: 45% of original goal descriptors were removed, and new goals and descriptors were added to enhance relevance and clarity.

Participants expressed that the patient-centric language of GOAL-Hēm empowered them in the goal-setting process and recognized its potential to measure meaningful clinical changes in their experiences with hemophilia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporating the patient voice and patient engagement in GOAL-Hēm: Advancing patient-centric hemophilia care. Roberts, JC., Recht, M., Gonzales, SE., et al.[2023]

Advancements in hemophilia treatment over the past 50 years have led to the availability of safe and effective factors VIII and IX, as well as integrated care models, but challenges remain in completely preventing joint bleeding and deterioration.

New recombinant clotting factors with extended half-lives may enhance treatment adherence and improve clinical outcomes by allowing for more convenient infusion schedules and better management of individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapies for hemophilia. Pipe, SW.[2018]

Recent advancements in haemophilia care, including improved treatment protocols and the use of recombinant factor VIII therapy, have significantly increased life expectancy and quality of life for patients, allowing them to transition to adulthood with healthier joints.

Despite these improvements, challenges remain, such as the short half-life of factor VIII requiring frequent re-administration and the development of inhibitors, prompting ongoing research to optimize treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemophilia care then, now and in the future. Oldenburg, J., Dolan, G., Lemm, G.[2018]

In a study analyzing claims data from 776 hemophilia A patients, it was found that patients using extended half-life (EHL) recombinant factor VIII (rFVIII) products dispensed significantly more international units (IUs) compared to those using standard half-life (SHL) products, with increases of 10% and 45% in two different databases.

Patients switched to EHL products experienced consistently higher expenditures, with costs being 51% to 122% greater than those using SHL products, indicating that while EHL may offer benefits in dosing frequency, it also leads to higher treatment costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Analysis of Dispensed International Units of Coagulation Factor VIII and Resultant Expenditures for Hemophilia A Patients: A Comparison Between Standard Half-Life and Extended Half-Life Products. Chhabra, A., Fogarty, PF., Tortella, BJ., et al.[2019]

Premofil M SRK demonstrated a mean in vivo recovery of factor VIII of 77%, indicating effective absorption and activity in patients with hemophilia.

The treatment showed a mean half-life of 11.9 hours and no reported side effects, confirming its safety and tolerability over several months of use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical testing of Premofil M SRK, a blood coagulation factor VIII concentrate purified from human plasma using monoclonal an antibodies]. Perret, BA., Poorbeik, M., Morell, A.[2006]

In a study involving 217 patients with severe to moderately severe hemophilia A, those treated with prophylaxis using recombinant factor VIII (REFACTO) experienced significantly fewer bleeding episodes (median of 4.4 per year) compared to those treated on-demand (median of 22.8 per year), highlighting the efficacy of prophylactic treatment.

The study reported a low incidence of serious adverse events (40% of patients), with only 2.8% developing inhibitors, indicating that REFACTO is generally safe and well-tolerated in the treatment of hemophilia A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and tolerability of recombinant factor VIII (REFACTO) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria. Pollmann, H., Externest, D., Ganser, A., et al.[2016]

In a study involving 3,000 to 4,000 hemophiliacs treated with Monoclate over two years, only 43 patients reported a total of 134 adverse events, indicating a low incidence of side effects.

Monoclate demonstrated an excellent safety profile, with no reports of viral transmission or unexpected adverse events, making it comparable to other factor VIII preparations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events reported in association with the use of monoclonal antibody purified factor VIIIC--Monoclate. Brown, DC.[2017]

Inhibitor development is a major complication in hemophilia A treatment, and genetic factors, particularly the type of F8 mutation, significantly influence the risk of developing inhibitors, especially in patients with a family history of inhibitors.

Recent studies suggest that initial intensive treatments increase the risk of inhibitors, while regular prophylaxis can provide a protective effect; a validated clinical score can help predict inhibitor risk based on genetic and treatment history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding inhibitor development in haemophilia A: towards clinical prediction and prevention strategies. Coppola, A., Santoro, C., Tagliaferri, A., et al.[2022]

BAY 94-9027, an extended half-life recombinant factor VIII, showed similar annualized bleeding rates (ABRs) compared to other FVIII agents while requiring significantly lower doses, indicating its efficacy in hemophilia A prophylaxis with potentially improved convenience for patients.

In a comparison using matched patient data, BAY 94-9027 demonstrated lower factor utilization than rFVIIIFc, BAX 855, and rAHF-PFM, suggesting it may be a more efficient treatment option for managing hemophilia A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of annualized bleeding rate and utilization of BAY 94-9027 versus three recombinant factor VIII agents for prophylaxis in patients with severe hemophilia A. Batt, K., Gao, W., Ayyagari, R., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Registry-based outcome assessment in haemophilia: a scoping study to explore the available evidence. [2022]

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

Incorporating the patient voice and patient engagement in GOAL-Hēm: Advancing patient-centric hemophilia care. [2023]

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

New therapies for hemophilia. [2018]

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

Haemophilia care then, now and in the future. [2018]

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

Real-World Analysis of Dispensed International Units of Coagulation Factor VIII and Resultant Expenditures for Hemophilia A Patients: A Comparison Between Standard Half-Life and Extended Half-Life Products. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Clinical testing of Premofil M SRK, a blood coagulation factor VIII concentrate purified from human plasma using monoclonal an antibodies]. [2006]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety and tolerability of recombinant factor VIII (REFACTO) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria. [2016]

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

Adverse events reported in association with the use of monoclonal antibody purified factor VIIIC--Monoclate. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Understanding inhibitor development in haemophilia A: towards clinical prediction and prevention strategies. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of annualized bleeding rate and utilization of BAY 94-9027 versus three recombinant factor VIII agents for prophylaxis in patients with severe hemophilia A. [2020]