NCT05265767CompletedPhase 1
Hematopoietic Stem Cell Transplantation Gene Therapy for Treatment of Severe Hemophilia A
Gene Therapy for Hemophilia A With a High Expression Factor VIII Transgene in Autologous Hematopoietic Stem Cells
Source: ClinicalTrials.gov · Last updated 12 Jul 2024
Brief summary (registry, in English)
Factor VIII (FVIII) is a large plasma glycoprotein that participates in blood coagulation. Loss of circulating FVIII activity due to mutations within the F8 gene results in the X-linked, recessive bleeding disorder hemophilia A. The clinical presentation ranges from a mild to severe bleeding phenotype that correlates with the patient's residual plasma FVIII activity level. Current state of the art treatment entails frequent infusion of FVIII protein. However, several limitations remain to treating hemophilia A, which are 1) access to FVIII-replacement products (currently \<30% of the world population is treated adequately, access is highly restricted in India), 2) high burden of compliance with treatment protocols particularly in children 3) the expense of FVIII-replacement products, 4) the development of humoral anti-FVIII immune responses that block FVIII activity and limit treatment efficacy and 5) morbidity due to crippling musculoskeletal disease when inadequately treated. Several newer hemostasis agents are being developed but like the recombinant Clotting Factor Concentrate (CFC) from the 1990s, these are also not likely to be made available in India for many years. Currently, the only cure for hemophilia A is orthotopic liver transplantation.
- Status (registry)
- Completed
- Phase (registry)
- Phase 1
- Study type
- Interventional
- Enrollment
- 6 (actual)
- First submitted
- 16 Feb 2022
- Start date
- 1 Apr 2022
- Primary completion date
- 28 Jun 2024
- Lead sponsor
- Christian Medical College, Vellore, India
- Diseases
- Haemophilia
- NCT number
- NCT05265767
What you commit to
- Study type: Interventional · Phase 1
- Participants enrolled: 6
- From 1 Apr 2022 to the primary completion date, 28 Jun 2024
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Significant organ dysfunction which could interfere with outcome of therapy such as: -
- Previous stem cell transplant.
- Use of medication(s) that can affect hemostasis (e.g. aspirin and non- cyclooxygenase (COX-2) selective non-steroid anti-inflammatory drugs).
Other illness
- History of spontaneous central nervous system bleeding within the last 5 years.
- History of a FVIII inhibitor (\>0.6 Bethesda Units/ml) including at least 2 measurements over the preceding 5 years or any single titer \>5 Bethesda Units (BU) /ml.
- HIV positive.
- Evidence of hepatitis B active infection or chronic carrier
- Evidence of chronic hepatitis C infection. Absence of chronic infection will be documented with at least 2 negative viral loads at least 6 months apart.
- Diagnosis of a bleeding disorder other than hemophilia A
- History of cancer or familial cancer syndromes
- Any condition in the opinion of the principle investigator that will negatively impact the subject's ability to safely undergo an autologous stem cell transplant.
Lab values
- Cardiac: There should be no evidence of significant cardiac dysfunction (resting left ventricular ejection fraction of \< 50%) and no cardiomegaly. There should not be uncontrollable hypertension.
- Renal: Glomerular Filtration Rate (GFR) \< 60 ml/min/1.73m2 as calculated using the Cockcroft-Gault equation.
- Hepatic: There should be no evidence of hepatic dysfunction which is defined as a serum bilirubin of \> 1.5 mg/dl and Aspartate Amino Transferase (AST) / Alanine Amino Transferase (ALT) \> 3X the upper limit of normal,
- Hematologic: Absolute neutrophil counts (ANC) \< 1000/mm3 and platelets counts \< 150,000/μL.
Other
- Pulmonary function with a corrected Diffusing Capacity of lung for Carbon Monoxide (DLCO) of \< 50% predicted
- Any reason in the opinion of the principle investigator that will negatively impact the subject's ability to complete the clinical trial per the trial protocol.
Who the study is looking for
- Able to provide informed consent for the protocol approved by the Institutional Review Board.
- Male subjects who are ≥18 years of age and \< 45 years of age.
- Diagnosis of severe hemophilia A (\<1 IU/dl factor VIII activity).
- Documented history of more than 100 exposures of factor VIII treatment.
- Average of at least 3 bleeds requiring treatment per year over the prior three years, at least 3 bleeds per year during the 3 years preceding the initiation of prophylaxis, or evidence of joint damage (knee, elbow or ankle) on physical or radiographic examination thought to be related to hemophilia.
- Performance status (Karnofsky score) of at least 70.
- Willing and able to comply with the requirements of the protocol.
Age in the registry: 18 years to 45 years · Sex: Male · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Christian Medical College Vellore Ranipet Campus Coordinator of this site? Confirm its status | Vellore | India | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.