Go-8: Gene Therapy for Hemophilia A Using a Novel Serotype 8 Capsid Pseudotyped Adeno-Associated Viral Vector Encoding Factor VIII-V3

Diseases Treated:

Hemophilia A

Eligibility Overview:

  • Male
  • At least 18 years old
  • Severe hemophilia A (less than 1% FVIII activity at baseline)
  • On factor prophylaxis or at least 4 bleeds per year or chronic hemophilic arthropathy
  • More than 50 exposure days to factor product

Brief Summary

Gene therapy offers the potential of persistent, endogenous production of FVIII following transfer of a normal copy of the cognate gene in a single therapeutic administration. Hemophilia A is especially well suited for gene therapy because the clinical manifestations are attributable to the lack of a single protein that circulates in minute amounts in the plasma.

Adeno-associated viral (AAV) vectors have shown the best safety profile among vectors of viral origin and can generate long-term gene expression, as illustrated by the success of an ongoing trial of AAV-mediated gene therapy for hemophilia B. In this trial, St. Jude Children’s Research Hospital and University College London (UCL) demonstrated stable expression of factor IX for up to six years without lasting toxicity in subjects with severe hemophilia B.

The GO-8 protocol uses a similar platform to test a new FVIII gene-containing AAV vector, developed by St. Jude and UCL. In recently published pre-clinical studies1, this vector has shown a high safety and potency record. GO-8 is now approved in the UK and is being submitted to regulatory authorities in the U.S. The trial should open in the U.S. by late spring, 2017. Clinicaltrials.gov number: NCT03001830

1(McIntosh J, Lenting PJ, Rosales C, et al. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant. Blood 2013;121:3335-3344).

Prescreening

St. Jude is currently prescreening potentially interested U.S. patients via a separate Screen Protocol to assess major eligibility criteria. Patients who choose to participate in prescreening may provide informed consent remotely via telephone.

Eligibility Criteria

Inclusion criteria include:

  • Male
  • At least 18 years old
  • Severe hemophilia A (less than 1% FVIII activity at baseline)
  • On factor prophylaxis or at least 4 bleeds per year or chronic hemophilic arthropathy
  • More than 50 exposure days to factor product

Exclusion criteria include:

  • Presence of inhibitor at time of enrollment or previous history of hFVIII inhibitor
  • Active hepatitis B or C
  • Inadequately treated HIV infection
  • AAV vector or any other gene transfer product received within previous 6 months
  • Uncontrolled glaucoma, diabetes mellitus or hypertension

Primary Objective

  • To assess the safety of systemic administration of novel, single-stranded AAV2/8-HLP-FVIII-V3 vector in adults with severe hemophilia A over three, escalating dose levels

Secondary Objectives

  • To establish data on level, kinetics and duration of FVIII expression, immunological responses and change in clinical outcomes

Study Design

Phase I/II, open label

Study Sites

University College London, UK and St. Jude Children’s Research Hospital, Memphis, Tennessee

GO-8 Quick View
Sponsors University College London, United Kingdom
ClinicalTrials.gov identifier NCT03001830
Estimated Enrollment 18
Study Type Interventional
Study Phase Phase I/II
Conditions Hemophilia A
Ages At least 18 years old
Principal investigator Pratima Chowdary, MD – University College London
Study Sites University College London, UK and St. Jude Children’s Research Hospital

Contact

Ulrike Reiss, MD
Department of Hematology
St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105 USA
Voice: 901-595-4753
Email: ulrike.reiss@stjude.org

Or

Jennifer Larkin, Study Coordinator
St. Jude Children’s Research Hospital
Voice: 901-595-2739
Email: jennifer.larkin@stjude.org