NCT03001830

Gene Therapy for Haemophilia A.

GO-8: Gene Therapy for Haemophilia A Using a Novel Serotype 8 Capsid Pseudotyped Adeno-associated Viral Vector Encoding Factor VIII-V3

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: University College, London · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The GO-8 study focuses on assessing safety and efficacy of gene therapy for patients with severe haemophilia A

Detailed description

Haemophilia A is an x-linked, life threatening bleeding disorder arising from defects in the coagulation factor VIII (FVIII) gene. Current treatment for haemophilia A, the commonest inherited bleeding disorder (prevalence of 1 in 5000 individuals) consists of life-long, 2-3 times/week, intravenous injection of clotting factor concentrates, which is demanding and expensive. In contrast, gene therapy offers the potential of a cure for haemophilia A. In a previous gene therapy study in haemophilia B the investigators showed that a single intravenous administration of a serotype 8 based adeno-associated virus, (AAV8) vector encoding the factor IX (FIX) gene resulted in stable (\>6 years) therapeutic expression of FIX without long-lasting toxicity. The investigators plan to use the same AAV8 platform to evaluate a novel FVIII expression cassette, AAV2/8-HLP-FVIII-V3, in patient with haemophilia A. Extensive preclinical studies demonstrate that AAV2/8-HLP-FVIII-V3 leads to long-term, endogenous expression of FVIII in mouse and non-human primate models without toxicity even when twenty-fold higher doses than the proposed starting clinical trial dose were used. Therefore, an open label, Phase I/II dose escalation study entailing a single systemic administration of AAV2/8-HLP-FVIII-V3 in adults (\>18 years of age) with severe haemophilia A who have baseline factor FVIII levels of \<1% of normal has been designed to establish safety and efficacy of our approach. Dosing will begin at 6x10\^11 vector genome (vg)/kg progressing sequentially to 2x10\^12vg/kg and ultimately 6x10\^12vg/kg in the absence of toxicity. A minimum of 2 patients will be recruited at each dose with a possibility of expanding the dose cohort to a maximum of 6 patients based on safety and efficacy. The study duration for each patient will be 5 years after vector infusion.

Conditions

• Hemophilia A

Interventions

Type	Name	Description
BIOLOGICAL	AAV2/8-HLP-FVIII-V3	Infusion of AAV2/8-HLP-FVIII-V3

Timeline

• Start date: 2017-06-14
• Primary completion: 2029-01-01
• Completion: 2029-12-01
• First posted: 2016-12-23
• Last updated: 2025-03-05

Locations

4 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study