Hematopoietic Stem Cell Transplantation Gene Therapy for Treatment of Severe Hemophilia A

Plain-language summary

This study investigates a gene therapy for severe hemophilia A in which the patient's own stem cells are corrected with a lentiviral vector carrying a factor VIII gene. It enrolled male patients aged 18-45 with very low factor VIII activity. The study was conducted in Phase 1 and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Completed

Sponsor

Christian Medical College, Vellore, India

Intervention

Auto CD34+PBSC transduced with a lentiviral vector encoding a novel coagulation factor VIII transgene

Start date

4/1/2022

Estimated completion

6/28/2024

Countries

India

Related genes

Locations

• Vellore, India

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

* 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.

Exclusion Criteria:

* History of spontaneous central nervous system bleeding within the last 5 years.
* Significant organ dysfunction which could interfere with outcome of therapy such as: -
* 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.
* Pulmonary function with a corrected Diffusing Capacity of lung for Carbon Monoxide (DLCO) of \< 50% predicted
* 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.
* Previous stem cell transplant.
* 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
* Use of medication(s) that can affect hemostasis (e.g. aspirin and non- cyclooxygenase (COX-2) selective non-steroid anti-inflammatory drugs).
* 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.
* 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.