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Gene Therapy for Fanconi Anemia, Complementation Group A

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04248439
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : January 30, 2020
Sponsor:
Information provided by (Responsible Party):
Rocket Pharmaceuticals Inc.

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.


Condition or disease Intervention/treatment Phase
Fanconi Anemia Complementation Group A Biological: RP-L102 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : February 2020
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2023


Arm Intervention/treatment
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
Biological: RP-L102
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04248439


Contacts
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Contact: Clinical Information 646-901-9276 FAclinicaltrial@rocketpharma.com

Locations
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United States, California
Stanford University Recruiting
Stanford, California, United States, 94304
Contact: Elisabeth Merkel       scgt_clinical_trials_office@lists.stanford.edu   
Sponsors and Collaborators
Rocket Pharmaceuticals Inc.
Investigators
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Principal Investigator: Sandeep Soni, MD Stanford University
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Responsible Party: Rocket Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT04248439    
Other Study ID Numbers: RP-L102-0319
First Posted: January 30, 2020    Key Record Dates
Last Update Posted: January 30, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rocket Pharmaceuticals Inc.:
anemia
bone marrow failure
gene therapy
Additional relevant MeSH terms:
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Fanconi Syndrome
Anemia
Fanconi Anemia
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors