What side effects are associated with this type of intervention?

Common treatments for Hemophilia A, such as prophylactic or on-demand replacement therapy with recombinant FVIII, often require frequent IV injections due to the short half-life of the therapeutics. Gene transfer therapy, like the one being studied with ASC618, aims to address this issue. Known side effects of gene transfer therapy using AAV vectors include immune responses to the viral vector, which can lead to inflammation and reduced efficacy of the treatment. Other side effects may include liver enzyme elevations and potential long-term risks that are still being studied. Overall, while gene therapy holds promise for reducing the frequency of treatments, it comes with its own set of potential adverse effects that need careful monitoring.

What prior FDA approvals exist?

The FDA has approved several treatments for Hemophilia A that focus on extending the half-life of factor VIII and improving its delivery. Notable approvals include Eloctate, a recombinant factor VIII fused with the Fc domain of human immunoglobulin, which extends its half-life by binding to the neonatal Fc receptor. Another example is PEGylated factor VIII, which involves covalent fusion with polyethylene glycol to prolong its activity. These treatments aim to reduce the frequency of injections and improve patient outcomes, similar to the goals of the ASC618 gene transfer therapy using an AAV vector encoding B-domain deleted codon-optimized human factor VIII.

What other types of research exist?

Promising alternatives to ASC618 for Hemophilia A patients include: 1) Recombinant factor VIII Fc fusion proteins, which have prolonged activity and reduced injection frequency. 2) Pegylated recombinant factor VIII, which also offers extended half-life and improved pharmacokinetics. 3) Other gene therapies under investigation, such as those using different viral vectors or gene editing technologies, which aim to provide long-term or permanent correction of the deficiency.

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Gene Therapy

Gene Therapy for Hemophilia A

Phase 1 & 2

Recruiting

Research Sponsored by ASC Therapeutics

Eligibility Criteria Checklist

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

Must have

Male ≥18 years of age

Received FVIII prophylactic or on-demand replacement therapy for ≥ 150 accumulated days (exposure days)

Must not have

Current antiviral therapy for hepatitis B or C

Current inhibitors, or history of high titer FVIII inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new gene therapy for hemophilia A patients. It uses a harmless virus to help liver cells produce a missing protein needed for blood clotting. This could reduce the need for frequent injections. The therapy aims to provide a long-term solution by enabling the body to produce the necessary protein on its own.

Who is the study for?

This trial is for male adults over 18 with severe or moderately severe hemophilia A, experiencing at least 12 bleeding episodes a year if on-demand therapy. They must have used replacement therapy for over 150 days and have a BMI of ≤30. Participants need to commit to using double-barrier contraception post-treatment until semen tests are negative.

What is being tested?

The study is testing ASC618, an advanced gene therapy designed to deliver a corrected form of the factor VIII gene to patients with hemophilia A. The goal is to reduce the frequency of bleeding episodes and treatment injections by enabling sustained production of factor VIII in the body.

What are the potential side effects?

Potential side effects may include immune reactions against the vector (AAV8), liver complications due to gene transfer, injection site reactions, and other unforeseen issues related to altering genes within the body.

Eligibility Criteria

Inclusion Criteria

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

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I am a man aged 18 or older.

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I have received FVIII therapy for at least 150 days.

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I have severe or moderately severe hemophilia A.

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I've had 12 or more bleeding episodes in the last year while on on-demand therapy.

Exclusion Criteria

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

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I am currently on medication for hepatitis B or C.

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I have or had high levels of Factor VIII inhibitors.

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My liver has significant scarring detected by a special scan.

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I do not have immunity to the AAV8 vector as tested by specific antibody tests.

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I have had heart surgery and need blood thinners.

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I have received gene therapy.

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I have a long-term kidney disease.

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I do not have an active infection or a condition that weakens my immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

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: ASC618Experimental Treatment1 Intervention

Experimental Arm

0 / 12Eligibility 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

The most common treatments for Hemophilia A include prophylactic or on-demand replacement therapy with recombinant factor VIII (FVIII) and gene transfer therapy. Replacement therapy involves regular intravenous infusions of recombinant FVIII to replace the deficient clotting factor, which helps prevent or control bleeding episodes. However, this requires frequent injections due to the short half-life of FVIII. Gene transfer therapy, such as the ASC618 trial, uses an adeno-associated virus (AAV) vector to deliver a codon-optimized human FVIII gene to the liver, enabling the body to produce its own FVIII. This approach aims to provide a long-term solution by reducing the need for frequent injections and maintaining stable FVIII levels, significantly improving the quality of life for Hemophilia A patients.

Gene Therapy for Hemophilia.Advances in Gene Therapy for Hemophilia.An adventure in biotechnology: the development of haemophilia A therapeutics -- from whole-blood transfusion to recombinant DNA to gene therapy.