Gene therapy offers the potential of persistent, endogenous production of factor VIII (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.
1(McIntosh J, Lenting PJ, Rosales C, et al. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encording a novel human factor VIII variant. Blood 2013;121:3335-3344).
Inclusion criteria include:
- 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
- Seropositive for HIV
- AAV vector or any other gene transfer product received within previous 6 months
- Uncontrolled glaucoma, diabetes mellitus or hypertension
- To assess the safety of systemic administration of a novel, single-stranded AAV2/8-HLP-FVIII-V3 vector in adults with severe hemophilia A over three, escalating dose levels
- To establish data on level, kinetics and duration of FVIII expression, immunological responses and change in clinical outcomes
Phase I/II, open label
University College London, UK and St. Jude Children’s Research Hospital, Memphis, Tennessee
About this study
This study will test the safety of a new study drug in patients with hemophilia A. This is an unproven treatment, and it will be the first time the drug has been used in humans.
Hemophilia A is a blood disorder that is found mostly in men. It is also known as factor VIII or factor 8 deficiency. Hemophilia A is a genetic disorder, which means it can be inherited. People with hemophilia A do not make enough factor VIII in their blood. Factor VIII helps the blood clot, or stop bleeding. People with hemophilia A bruise easily and often bleed into their joints and soft tissues.
Standard treatment for hemophilia A is regular intravenous (through a vein) infusions of factor VIII protein concentrate to help the blood clot normally.
In this study, doctors will use a new procedure to help you make your own factor VIII. They will take a factor VIII gene and carry it to the liver using a vector. A vector is a virus that has been inactivated and can no longer cause an infection. This type of treatment is called gene therapy.
Purpose of this clinical trial
The main goal of this study is to test the safety and effectiveness of the study drug at different doses to find out what effects, if any, it has on people.
- At least 18 years old
- Severe hemophilia A
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
Ulrike Reiss, MD – St. Jude Children’s Research Hospital
Study Sites University College London, UK and St. Jude Children’s Research Hospital For a consultation or to discuss GO-8 St. Jude Physician/Patient Referral Office
Jennifer Larkin, Study Coordinator
St. Jude Children’s Research Hospital