What side effects are associated with this type of intervention?

The most common treatments for Hemophilia A, such as recombinant factor VIII products, can cause side effects including the development of inhibitors (antibodies that neutralize the effectiveness of the treatment), allergic reactions, and injection site reactions. Gene therapy, which aims to introduce a functional gene to produce clotting factor VIII, is still under investigation but has shown potential side effects such as immune responses to the viral vector used for gene delivery, liver enzyme elevations, and the risk of insertional mutagenesis. Patients should discuss these potential risks with their healthcare provider to make informed decisions about their treatment options.

What prior FDA approvals exist?

The FDA has approved several treatments for Hemophilia A, including recombinant factor VIII products designed to replace the missing clotting factor. Notable approvals include rFVIII-Fc (Eloctate), which fuses factor VIII with the Fc domain of immunoglobulin to extend its half-life, and PEGylated factor VIII, which uses polyethylene glycol to prolong activity. Gene therapy approaches, such as those studied in the GO-8 trial, aim to introduce functional genes to produce clotting factor VIII, offering a potential long-term solution for patients with severe Hemophilia A.

What other types of research exist?

Promising alternatives to gene therapy for Hemophilia A patients in 2024 include: 1) Long-acting recombinant factor VIII products, which offer extended half-life and reduced infusion frequency. 2) Recombinant factor VIII Fc fusion proteins, which enhance the stability and duration of clotting activity. 3) Non-factor therapies such as emicizumab, a bispecific antibody that mimics the function of factor VIII and can be administered subcutaneously. These options provide effective and convenient treatment alternatives for managing Hemophilia A.

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Virus Therapy

Gene Therapy for Hemophilia A (GO-8 Trial)

Phase 1 & 2

Recruiting

Led By Pratima Chowdary, MD

Research Sponsored by University College, London

Eligibility Criteria Checklist

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

Must have

Adult males, ≥ 18 years of age with confirmed diagnosis of severe HA resulting from gene mutations that have a low risk for inhibitor development

Severe bleeding phenotype as defined by prophylaxis for a history of bleeding or on demand therapy with a current or past history of 4 or more bleeding episodes/year or evidence of chronic haemophilic arthropathy

Must not have

Evidence of liver dysfunction (persistently elevated ALT >1.5X upper limit of normal)

Poor performance status (WHO score >1)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up annual review for 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a gene therapy that uses a harmless virus to deliver a healthy gene to adults with severe haemophilia A. The goal is to help their bodies produce a missing blood-clotting protein, potentially curing their condition. Gene therapy for hemophilia has been explored for many years, with several programs in advanced stages.

Who is the study for?

Adult males over 18 with severe Hemophilia A, who have used hFVIII concentrates for more than 50 days and suffer from frequent bleeding or joint damage due to bleeding. Participants must be able to follow the trial procedures for five years and use barrier contraception post-treatment until semen tests confirm safety.

What is being tested?

The GO-8 study is testing a gene therapy called AAV2/8-HLP-FVIII-V3 in men with severe Hemophilia A. It aims to evaluate how safe and effective this treatment is over time.

What are the potential side effects?

Potential side effects are not explicitly listed but may include reactions related to the body's immune response against the new gene or the viral vector used, liver dysfunction, increased risk of blood clots, or other unforeseen complications.

Eligibility Criteria

Inclusion Criteria

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

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I am a man over 18 with severe hemophilia A due to low-risk gene mutations.

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I have a severe bleeding disorder with frequent bleeding episodes or joint damage due to bleeding.

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I have been treated with hFVIII for over 50 days.

Exclusion Criteria

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

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My liver tests show higher than normal levels.

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My health limits my daily activities significantly.

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I have severe haemophilia A with specific genetic changes.

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I do not have uncontrolled heart failure or unstable chest pain.

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I have had tuberculosis, fungal disease, or another long-term infection.

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I do not have uncontrolled glaucoma, diabetes, or high blood pressure.

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My liver ultrasound showed a possible cancer sign.

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I have active hepatitis B or C, or I am on antiviral therapy for it.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ annual review for 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~annual review for 5 years

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

Treatment Details

Study Objectives

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

Primary study objectives

Safety - Dose Limiting Toxicity possibly attributable to the gene therapy

Safety - Neutralising anti-hFVIII antibody development following gene therapy

Secondary study objectives

Bleeding frequency

Immune response to the AAV8 capsid.

Plasma hFVIII activity

+2 more

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: Treatment ArmExperimental Treatment1 Intervention

Treatment with AAV2/8-HLP-FVIII-V3

0 / 11Eligibility 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 recombinant factor VIII, desmopressin, and gene therapy. Recombinant factor VIII works by replacing the missing or defective clotting factor VIII, which is crucial for blood clotting. Desmopressin stimulates the release of stored factor VIII from blood vessel linings, temporarily increasing its levels. Gene therapy introduces a functional gene to produce clotting factor VIII, potentially offering a long-term solution by enabling the patient's body to produce the necessary clotting factor. These treatments are vital for Hemophilia A patients as they help manage bleeding episodes and prevent joint damage, significantly improving quality of life.