- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03818763
Gene Therapy Trial for Platelet Derived Factor VIII Production in Hemophilia A
Phase I Study Evaluating Safety and Feasibility of Hematopoietic Stem Cell Gene Transfer That Targets Factor VIII Delivery From Platelets for Patients With Hemophilia A
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Mary Eapen, MD
- Phone Number: 414-805-0700
- Email: meapen@mcw.edu
Study Contact Backup
- Name: Arielle Baim
- Phone Number: 414-805-8745
- Email: abaim@mcw.edu
Study Locations
-
-
Wisconsin
-
Milwaukee, Wisconsin, United States, 53226
- Recruiting
- Froedtert Hospital and the Medical College of Wisconsin
-
Contact:
- Mary Eapen, MD
- Phone Number: 414-805-0700
- Email: meapen@mcw.edu
-
Contact:
- Arielle Baim
- Phone Number: 414-805-8745
- Email: abaim@mcw.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Study population will include: adult males >18 years of age with a diagnosis of severe hemophilia A and currently active or a history of FVIII inhibitors (≥0.6 BU). Females will be excluded because hemophilia A is an X-linked disorder that is extremely rare in females.
- 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.
- Subject must be willing and able to document type of bleeding episodes and treatment in a paper or electronic diary during the study.
- Subject must be willing to return for regular follow-up visits during the 15-year study.
Exclusion Criteria:
A potential subject who meets any of the following exclusion criteria is ineligible to participate in the study.
- 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:
- FV Leiden
- Protein S deficiency
- Protein C deficiency
- Prothrombin mutation (G20210A)
- D-dimer >3 x the upper limit of normal (ULN) at Screening All known patients with the above and any patient with a personal or significant family history of thrombotic events (DVT, PE, arterial clots) as deemed by the principal investigator will be screened for the above disorders.
- 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.
- Life expectancy severely limited by disease(s) other than hemophilia A.
- Patients with HIV, hepatitis B, hepatitis C (with an AST/ALT > 3 times the upper limit of normal).
- Other active infectious disease that is a contraindicat ion for immunosuppressive therapy.
- Patients who have elective surgery scheduled during the study period.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Autologous CD34+PBSC transduced with a lentiviral vector
Patients will receive a patient specific (autologous) cytokine mobilized CD34+Peripheral Blood Stem Cells (PBSC) transduced ex vivo with a lentiviral vector containing cDNA encoding the human B-domain deleted FVIII protein.
|
Reduced intensity conditioning with melphalan and fludarabine, followed by a single infusion of autologous CD34+PBSC, transduced with a lentiviral vector (-889ITGA2B-BDDFVIII-WPTS(MUT6)(VSVg)) also known as (Pleightlet(MUT6)) encoding the B domain deleted from of human coagulation factor VIII (BDDFVIII) in up to five hemophilia A patients with a history of FVIII inhibitors (≥0.6BU). The infusion volume of transduced cells will not exceed 20 ml/kg body weight. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of enrolled participants with adequate gene transduced hematopoietic stem cells for FVIII gene therapy infusion
Time Frame: Through study completion, an average of 4 years
|
Assessed by availability of ≥4x106 transduced clinical grade CD34+PBSC per kg meeting release criteria for infusion; undetectable microbiological contamination and cell viability ≥70%.
|
Through study completion, an average of 4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of toxicity from gene therapy
Time Frame: Within 3 months of gene therapy infusion
|
Number of events meeting CTCAE criteria grade 3 or 4 toxicity
|
Within 3 months of gene therapy infusion
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mary Eapen, MD, Froedtert Hosptial and Medical College of Wisconsin
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO00033763
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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