Gene Therapy Trial for Platelet Derived Factor VIII Production in Hemophilia A (NCT03818763) | Clinical Trial Compass
Active — Not RecruitingPhase 1
Gene Therapy Trial for Platelet Derived Factor VIII Production in Hemophilia A
United States5 participantsStarted 2020-04-29
Plain-language summary
This is a Phase I study. This research study is being conducted to find new ways to treat severe hemophilia A. This study is a gene therapy study. Gene therapy is an experimental way to introduce, into a person's cells, specific genetic material. A gene can be delivered/introduced into a cell using a carrier known as a "vector." In this study, a virus (lentivirus), the "vector", is used to introduce or deliver a gene that creates and stores a protein Factor VIII (FVIII) in your platelets. These platelets are made from stem cells (mother cells for your bone marrow) that are removed from your blood by a procedure called apheresis. This research study will take some of the patient's own stem cells, from the apheresis procedure, and genetically modify them using the vector in order to make them produce FVIII in platelets that arise from the stem cells. They will then give the genetically modified stem cells back to the patient so that they can possibly create platelets that produce and store Factor VIII on their own.
Who can participate
Age range18 Years
SexMALE
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Inclusion criteria
✓. Confirmed diagnosis of severe hemophilia A by undetectable plasma factor VIII:C by a one-stage PTT-based assay and coatest chromogenic factor VIII assay. Subjects with currently active or a history of positive FVIII inhibitor titers (≥0.6 BU) irrespective of their titer or current inhibitor status will be included for enrollment.
✓. Subject may be prescribed prophylactic therapy with factor VIII bypassing agents or factor VIII mimetics prior to referral for inclusion in the study.
✓. Subjects who are treated on demand using factor VIII bypassing agents must have a history of four or more bleeding episodes requiring treatment in the six-month period prior to referral for inclusion in the study.
✓. Adequate bone marrow reserve as demonstrated by ANC \>1.5/cu.mm; Hemoglobin \>9g/dL; Platelets \>100,000/microliter.
✓. Adequate renal function, defined as creatinine clearance\>60 ml/min (Cockroft-Gault formula)
✓. Adequate liver function, defined as defined as total bilirubin ≤1.5 times the upper limit of normal (ULN) (excluding Gilbert's syndrome), both AST and ALT ≤3 times ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis.
✓. Subject must sign an informed consent after explanation of the study and having questions answered.
What they're measuring
1
Number of enrolled participants with adequate gene transduced hematopoietic stem cells for FVIII gene therapy infusion
Timeframe: Through study completion, an average of 4 years
. Subject must be willing and able to document type of bleeding episodes and treatment in a paper or electronic diary during the study.
Exclusion criteria
✕. Therapy with factor VIII with the intent of immune tolerance induction within 30 days prior to inclusion within the study.
✕. Enrollment in another interventional clinical trial within 60 days prior to study inclusion.
✕. Medical contraindication to PBSC cytokine mobilization, use of GCSF, PBSC apheresis procedure or conditioning regimen.
✕. Medically significant organ dysfunction that would prevent compliance with conditioning or would severely limit the probability of survival based on clinical status.
✕. Those with a known co-existing clinically significant thrombophilic disorder, or as determined by the presence of any of the below identified on screening laboratory assessments:
✕. Active invasive malignancy (Non-melanoma skin cancers and carcinoma in situ are not excluded).
✕. Known bone marrow disorders or abnormal bone marrow cytogenetics.
✕. Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment.