Gene therapy for hemophilia A in adults

Clinical Exploration of Clinical Exploration Adeno-associated Virus Vector Expression of Human Coagulation Factor VIII Gene Therapy for Hemophilia A

This study is testing a new gene therapy to see if it can safely help adults with hemophilia A who have very low levels of a crucial clotting factor.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT04728841 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and kinetics of a single intravenous infusion of GS001 in adult patients with hemophilia A who have very low levels of FVIII. It is an open-label, non-randomized trial where the first patient will receive a specific dose of GS001, followed by adjustments based on safety assessments and FVIII activity levels. The study aims to determine the appropriate dosing and monitor the effects of the gene therapy over time.

Who should consider this trial

Good fit: Ideal candidates are adult males aged 18 and older with hemophilia A and residual FVIII levels of ≤1 IU/dL.

Not a fit: Patients with FVIII levels above 1 IU/dL or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this gene therapy could significantly improve the management of hemophilia A by potentially restoring FVIII levels in patients.

How similar studies have performed: Other studies have shown promise with gene therapy approaches for hemophilia, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Be able to understand the purpose and risks of the study and provide informed consent according to national and local privacy laws;
2. Male subjects and ≥ 18 years of age;
3. Have hemophilia A with ≤1 IU/dL (≤1%) endogenous FVIII activity levels at the time of screening. If the screening result is \>1% due to previous treatment with FVIII product, then it may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤1% FVIII activity levels ;
4. No history of hypersensitivity or anaphylaxis associated with FVIII product administration;
5. Have no measurable FVII inhibitor as assessed by laboratory two times that were at least one week apart; or documented no prior history of FVIII inhibitor after 150 EDs and no clinical signs or symptoms of decreased response to FVIII infusion ;
6. Have acceptable laboratory values sampled at screening and repeated prior to Day 0; A. Hemoglobin ≥ 11 g/dL; B. Platelets ≥ 100 x 10\^9/L; C. AST, ALT, alkaline phosphatase ≤ 1.25 upper limit of normal (ULN); D. Bilirubin ≤ 1.25 ULN; E. Creatinine ≤ 2 mg/dL.
7. Agree to use reliable barrier contraception until the end of the 52 weeks observation period, and three consecutive semen samples are negative for vector sequences after GS001 infusion.

Exclusion Criteria:

1. Have Hepatitis B, hepatitis C or HBsAg, HCVAb, HBV-DNA, HCV-RNA are positive and have clinical significance. Both natural clearers and those who have cleared HCV on antiviral therapy are deemed eligible;
2. Currently Receiving antiviral therapy for hepatitis B and C;
3. Have history of chronic infections or other chronic diseases that may pose a risk to the study participation;
4. Have participated in a previous gene therapy research trial within the last 52 weeks or in a clinical study with an investigational drug within the past 30 days;
5. The subject has any concurrent diseases that cannot tolerate treatments of prednisone or prednisolone as judged by the investigator;
6. History of arterial or venous thromboembolic events (e.g., deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolism);
7. Known inherited or acquired thrombophilia, including conditions associated with increased risk of thromboembolism, such as atrial fibrillation;
8. Major surgery planned in 1 year period following the infusion with GS001;
9. Hypersensitivity to the study vector;
10. Have clinically major diseases or any other unspecified conditions that, in the opinion of the Investigator, makes the subject unsuitable for participating in the study;
11. Patients who are unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
12. Evidence of other bleeding disorders not associated with hemophilia A.

Where this trial is running

Tianjin, Tianjin Municipality

• Chinese Academy of Medical Science and Blood Disease Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Lei Zhang, MD — Chinese Academy of Medical Science and Blood Disease Hospital
• Study coordinator: Wei Liu, MD

Conditions Hemophilia A; Gene Therapy