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Gene Therapy for Fanconi Anemia, Complementation Group A

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ClinicalTrials.gov Identifier: NCT04248439
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : November 24, 2020
Sponsor:
Information provided by (Responsible Party):
Rocket Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE January 24, 2020
First Posted Date  ICMJE January 30, 2020
Last Update Posted Date November 24, 2020
Actual Study Start Date  ICMJE July 15, 2020
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 28, 2020)
Phenotypic correction of bone marrow colony forming units after infusion of RP-L102 [ Time Frame: 3 years ]
During months 12-36 post-infusion, the survival of bone marrow colony forming units to 10nM mitomycin C (MMC) increases to over or equal to 10% with respect to values determined at baseline (pretreatment evaluation).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2020)
  • Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102 [ Time Frame: 3 years ]
    Assessment of the percentage of peripheral blood T-cells with diepoxybutane (DEB)-induced chromosomal aberrations
  • Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102 [ Time Frame: 3 years ]
    The level of gene marking of the FANCA-lentiviral vector (LV) provirus in total peripheral blood cells is at least 0.1 vector copy number (VCN) in peripheral blood cells during months 12-36 post-infusion
  • Prevention or rescue of bone marrow failure after infusion of RP-L102 [ Time Frame: 3 years ]
    Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Therapy for Fanconi Anemia, Complementation Group A
Official Title  ICMJE A Phase 2 Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A
Brief Summary

The objective of this study is to assess the therapeutic efficacy of a hematopoietic cell-based gene therapy for patients with Fanconi anemia, subtype A (FA-A).

Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral vector carrying the FANCA gene. After transduction, the corrected stem cells will be infused intravenously back to the patient with the goal of preventing bone marrow failure.

Detailed Description

This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A.

Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fanconi Anemia Complementation Group A
Intervention  ICMJE Biological: RP-L102
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene
Study Arms  ICMJE Experimental: RP-L102
RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene
Intervention: Biological: RP-L102
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 28, 2020)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2023
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of DEB or a similar DNA-crosslinking agent
  2. Patients of the complementation group FA-A
  3. Minimum age: 1 year and a minimum weight of 8 kg
  4. At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3 months prior to CD34+ cell collection OR (see subsequent criterion)
  5. If the number of CD34+ cells/ μL in BM is in the range of 10-29, peripheral blood (PB) parameters should meet two of the three following criteria:

    • Hemoglobin: ≥11g/dL
    • Neutrophils: ≥900 cells/μL
    • Platelets: ≥60,000 cells/μL
  6. Provide informed consent in accordance with current legislation
  7. Women of childbearing age must have a negative urine pregnancy test at the baseline visit, and accept the use of an effective contraception method during participation in the trial

Exclusion Criteria:

  1. Subjects with an available and medically eligible HLA-identical sibling donor.
  2. Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those reported as variant(s) of normal in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the subject commences the stem cell mobilization/collection procedures of the clinical trial.
  3. Subjects with somatic mosaicism associated with stable or improved counts in all PB cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease (≥1 NCI CTCAE grade) in at least one blood lineage over time must be documented to enable eligibility, as should <5% resistance of bone marrow colony forming cells (CFCs) to 10nM MMC; whenever possible potential mosaicism should also be evaluated by gene sequencing of MMC-resistant CFCs).
  4. Lansky performance status ≤60%.
  5. Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study.
  6. Pre-existing sensory or motor impairment ≥grade 2 according to the criteria of the NCI.
  7. Pregnant or breastfeeding women.
  8. Hepatic dysfunction as defined by either:

    • Bilirubin >3.0 × the upper limit of normal (ULN) or
    • Alanine aminotransferase (ALT) > 5.0 × ULN or
    • Aspartate aminotransferase (AST) > 5.0 × ULN

    For subjects with bilirubin, ALT or AST above ULN, a workup to identify the etiology of liver abnormality should be conducted prior to confirmation of eligibility as stipulated in exclusion criterion 5, including evaluation of viral hepatitis, iron overload, drug injury or other causes.

  9. Renal dysfunction requiring either hemodialysis or peritoneal dialysis.
  10. Pulmonary dysfunction as defined by either:

    • Need for supplemental oxygen during the prior 2 weeks in absence of acute infection or
    • Oxygen saturation by pulse oximetry <90%.
  11. Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years.
  12. Subject is receiving androgens (i.e. danazol, oxymetholone).
  13. Subject is receiving other investigational therapy for treatment/prevention of FA-associated bone marrow failure.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Information 646-627-0033 FAclinicaltrial@rocketpharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04248439
Other Study ID Numbers  ICMJE RP-L102-0319
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rocket Pharmaceuticals Inc.
Study Sponsor  ICMJE Rocket Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Agnieszka Czechowicz, MD Stanford University
Principal Investigator: Margaret MacMillan, MD, MSc University of Minnesota
PRS Account Rocket Pharmaceuticals Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP