Gene therapy for Haemophilia A

Phase 1

Completed

Conditions: Health Condition 1: null- Haemophilia AHealth Condition 2: D682- Hereditary deficiency of other clotting factors

Registration Number: CTRI/2022/03/041304

Lead Sponsor: Centre for stem cell Research A Unit of inStem Bengaluru

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

1.Able to provide informed consent for the protocol approved by the Institutional Review Board.

2.Male subjects who are = 45 years of age and have completed family with children. Upper limit of < 55 years of age

3.Patients who have high AAV antibody titers which makes them ineligible for participation in other AAV gene therapy clinical trials

4.Diagnosis of severe hemophilia A ( <1 IU/dl factor VIII activity).

5.Documented history of more than 100 exposures of factor VIII treatment.

6.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.

7.Performance status (Karnofsky score) of at least 70

8.Willingness to use barrier contraception or limit sexual intercourse to post-menopausal, surgically sterilized, or contraception-practicing partners, for 100 days after transplantation.

9.Willing and able to comply with the requirements of the protocol.

Exclusion Criteria

1.History of spontaneous central nervous system bleeding within the last 5 years.

2.Significant functional deficits in major organs which would interfere with successful outcome following autologous stem cell transplant, the following guidelines will be utilized:

Cardiac: There should be no evidence of significant cardiac dysfunction (resting left ventricular ejection fraction of < 50%) and no marked cardiomegaly. There should not be uncontrollable hypertension.

Renal: 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 AST/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 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 BU/ml.

5.Previous stem cell transplant.

6.HIV or RPR positive.

7.Patients who have allergic reactions to lupine ATG

8.Evidence of hepatitis B active infection or chronic carrier

9.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.

10.Diagnosis of a bleeding disorder other than hemophilia A

11.Use of medication(s) that can affect hemostasis (e.g. aspirin and non-COX-2 selective non-steroid anti-inflammatory drugs).

12.History of cancer or familial cancer syndromes (e.g. leukemia, colorectal cancer).

13.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.

14.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.