What side effects are associated with this type of intervention?

Common treatments for Hemophilia A, such as gene therapy (e.g., Valoctocogene Roxaparvovec) and recombinant factor VIII, have several known side effects. Gene therapy can cause immune responses to the viral vector, liver enzyme elevations, and potential long-term risks that are still under investigation. Recombinant factor VIII treatments may lead to the development of inhibitors against factor VIII, allergic reactions, and infusion-related reactions. Both treatments aim to manage bleeding but come with specific risks that need to be monitored.

What prior FDA approvals exist?

The FDA has approved several treatments for Hemophilia A, focusing on enhancing or replacing Factor VIII (FVIII). One notable approval is for recombinant FVIII products, such as Factor VIII-Fc fusion (rFVIII-Fc; Eloctate), which extends the half-life of FVIII, allowing for less frequent dosing. Another advanced treatment is the use of gene therapy, such as valoctocogene roxaparvovec, which aims to introduce a functional FVIII gene into patients. This approach is currently under clinical investigation and represents a significant advancement in potentially providing a long-term solution for Hemophilia A by enabling the patient's body to produce FVIII naturally.

What other types of research exist?

Promising alternatives to Valoctocogene Roxaparvovec for Hemophilia A patients include: 1) Etranacogene dezaparvovec, a gene therapy for Hemophilia B that may have implications for Hemophilia A; 2) Recombinant factor VIII products with extended half-lives, such as those linked with albumin or PEGylated to prolong activity; 3) Nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX, which, while primarily for Hemophilia B, represents advancements in factor replacement therapies that could be adapted for Hemophilia A.

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Gene Therapy

Gene Therapy for Hemophilia A (GENEr8-INH Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for Hemophilia A primarily aim to replace or bypass the deficient factor VIII (FVIII) to prevent or control bleeding episodes. Recombinant factor VIII products directly replace the missing FVIII, allowing the blood to clot properly. Bypassing agents like activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa) work by activating the clotting cascade downstream of FVIII, effectively bypassing the need for FVIII. Gene therapy, such as valoctocogene roxaparvovec, introduces a functional FVIII gene into the patient's cells, enabling the body to produce its own FVIII. This approach has the potential to provide a long-term solution by addressing the underlying genetic cause of Hemophilia A. These treatments are crucial for managing bleeding risks and improving the quality of life for patients with Hemophilia A.

Phase 1 & 2

Waitlist Available

Research Sponsored by BioMarin Pharmaceutical

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Part A: Demonstrated no immunological tolerance to exogenous FVIII. Part B: Demonstrated tolerance to exogenous FVIII and negative FVIII inhibitor screening titer < 0.6 BU.

Be older than 18 years old

Must not have

Evidence of any bleeding disorder not related to hemophilia A.

Currently undergoing, or plan to receive during the study, immune tolerance induction therapy or prophylaxis with FVIII (Part A only).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a gene therapy called valoctocogene roxaparvovec in patients with severe haemophilia A who have developed antibodies against standard treatments. The therapy aims to provide a working version of the gene needed for proper blood clotting.

Who is the study for?

This trial is for adult males with severe Hemophilia A who have had inhibitors to Factor VIII. They must not drink alcohol for a year post-treatment, use effective contraception, and cannot have other bleeding disorders or significant organ dysfunction. Part A includes those currently with inhibitors; Part B is for those with a past history of inhibitors.

What is being tested?

The study tests the safety and effectiveness of Valoctocogene Roxaparvovec in two groups: one with active Factor VIII inhibitors (Part A) and another that previously had these inhibitors but now tolerates FVIII (Part B).

What are the potential side effects?

Potential side effects may include immune reactions to the treatment, liver issues due to viral vector used in gene therapy, injection site reactions, headaches, fatigue, muscle pain and possibly new inhibitor development.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a bleeding disorder that is not hemophilia A.

Select...

I am receiving or plan to receive immune therapy for FVIII during the study.

Select...

I do not have severe kidney, liver problems, infections, or a history of liver cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 60 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270.

Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270.

Change of the median Factor VIII activity.

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Valoctocogene roxaparvovec Open LabelExperimental Treatment1 Intervention

Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg in Active Inhibitor Population (Part A) and Prior Inhibitor Population (Part B).

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Hemophilia A primarily aim to replace or bypass the deficient factor VIII (FVIII) to prevent or control bleeding episodes. Recombinant factor VIII products directly replace the missing FVIII, allowing the blood to clot properly. Bypassing agents like activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa) work by activating the clotting cascade downstream of FVIII, effectively bypassing the need for FVIII. Gene therapy, such as valoctocogene roxaparvovec, introduces a functional FVIII gene into the patient's cells, enabling the body to produce its own FVIII. This approach has the potential to provide a long-term solution by addressing the underlying genetic cause of Hemophilia A. These treatments are crucial for managing bleeding risks and improving the quality of life for patients with Hemophilia A.