Status:
NOT_YET_RECRUITING
Hematopoietic Stem Cell Transplantation Gene Therapy for Treatment of Severe Hemophilia A
Lead Sponsor:
Expression Therapeutics, LLC
Conditions:
Hemophilia A
Eligibility:
MALE
18+ years
Phase:
PHASE1
Brief Summary
This is a first-in-human, non-randomized, open label, single treatment, Phase 1 study in approximately 7 patients with severe hemophilia A. The study will evaluate gene therapy by transplantation of a...
Detailed Description
Eligible subjects will undergo CD34+ hematopoietic stem cell collection. These cells will be transduced ex vivo with CD68-ET3 lentiviral vector and subsequently, following a conditioning regimen of bu...
Eligibility Criteria
Inclusion
- Able to provide informed consent for the protocol approved by the Institutional Review Board.
- Male subjects who are \>= 18 years of age.
- Diagnosis of severe hemophilia A (\<1 IU/dL factor VIII activity) based on one-stage coagulation assay.
- Documented history of more than 150 days of factor VIII treatment.
- Average of at least 4 bleeds requiring treatment per year over the prior three years, or at least 4 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.
- Willingness to use effective barrier contraception or limit sexual intercourse to postmenopausal, surgically sterilized, or contraception-practicing partners, for 12 weeks (3 months) after transplantation.
- Willing and able to comply with the requirements of the protocol.
Exclusion
- History of spontaneous central nervous system bleeding within the last 5 years.
- 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 per local institutional standard such as CKD-EPI creatinine equation or equivalent.
- Hepatic: There should be no evidence of hepatic dysfunction which is defined as a serum total bilirubin of \> 1.5 mg/dL and AST/ALT \> 3X the upper limit of normal.
- Hematologic: Absolute neutrophil counts (ANC) \<1000/ µL or platelets counts \< 150,000/µL.
- Pulmonary function with a corrected carbon monoxide diffusing capacity (cDLCO) \< 50% predicted.
- History of a fVIII inhibitor (\> 0.4 Bethesda Units/mL) including at least 2 measurements done at least a week apart or any single titer \> 5 BU/mL.
- Subjects who have had prior cellular based therapy or gene editing/ gene therapy including a previous stem cell transplant.
- Subjects with any evidence of active infection or any immunosuppressive disorder, including currently detectable HIV viral load
- Subjects who are RPR, anti-HTLV-1 and II antibody, CMV PCR, VZV antibody and HSV PCR positive at screening.
- Subjects who have allergic reactions or hypersensitivity to any of the drugs used in the study (i.e., anti-thymocyte globulin, plerixafor, G-CSF, busulfan, levetiracetam) or to the constituents of the investigational product formulation.
- Evidence of hepatitis B active infection or chronic carrier based on a positive Hepatitis B DNA testing at screening.
- Positive (detectable viral load per local institutional standard) for the presence of Hepatitis C virus (HCV). Subjects who are positive for anti-HCV antibody are eligible as long as they have a negative undetectable HCV viral load at screening.
- Subjects diagnosed with any history of clinically relevant coagulation or bleeding disorder other than hemophilia A.
- Use of medication(s) that can affect hemostasis (e.g. aspirin, ibuprofen and non-COX-2 selective non-steroid anti-inflammatory drugs).
- Subjects with a history of a malignancy (except surgically resected non-melanoma skin cancer) or subjects with a family history of a known cancer syndrome in a first degree relative.
- Planned surgery within 6 months of enrollment (other than study procedures).
- Treatment with any live vaccines or systemic immunosuppressive agents, not including corticosteroids within 30 days before CD68-ET3-LV CD34+ infusion.
- Treatment with any investigational product within 30 days or 5 half-lives of the investigational product (whichever is longer) prior to enrollment.
- History of autoimmune disease (e.g., inflammatory bowel disease, systemic lupus erythematosus, vasculitis).
- Concurrent enrollment in another clinical study, which might interfere with the requirements of this study or have the potential to impact the evaluation of safety and efficacy of CD68-ET3-LV CD34+- unless it is a non-interventional observational study.
- Any condition in the opinion of the Study Investigators that will negatively impact the subject's ability to safely undergo an autologous stem cell transplant.
- Any reason in the opinion of the Study Investigators that will negatively impact the subject's ability to complete the clinical trial per the trial protocol.
Key Trial Info
Start Date :
September 1 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 1 2039
Estimated Enrollment :
7 Patients enrolled
Trial Details
Trial ID
NCT04418414
Start Date
September 1 2024
End Date
August 1 2039
Last Update
February 20 2024
Active Locations (0)
Enter a location and click search to find clinical trials sorted by distance.
No Results Found
We couldn’t find results for the location/zipcode entered or within the selected range. Please check your input or adjust your search.