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A Clinical Trial to Evaluate the Safety of RP-L102 in Pediatric Subjects With Fanconi Anemia Subtype 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. Read our disclaimer for details. Identifier: NCT03814408
Recruitment Status : Active, not recruiting
First Posted : January 24, 2019
Last Update Posted : June 25, 2019
Information provided by (Responsible Party):
Rocket Pharmaceuticals Inc.

Brief Summary:
The objective of this study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with Fanconi anemia subtype A (FA-A).

Condition or disease Intervention/treatment Phase
Fanconi Anemia Complementation Group A Biological: RP-L102 Phase 1

Detailed Description:

This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral vector and infused following transduction, without any prior conditioning. After transduction, product quality control evaluations will be carried out in aliquots of the transduced population. Investigational product will be infused via intravenous infusion with no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered optimal.

The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene and the therapeutic product is subject's autologous HSCs that have been transduced with the lentiviral vector. The vector contains the functional FANCA gene.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A
Actual Study Start Date : January 11, 2019
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : March 2022

Arm Intervention/treatment
Experimental: RP-L102
RP-L102 is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene
Biological: RP-L102
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE

Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0 [ Time Frame: 3 years ]
    Evaluation of safety associated with treatment with RP-L102

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 DEB-induced chromosomal aberrations that decreases from over or equal to 50% at 0-2 months post-infusion to less than 50% during months 6-36 post-infusion (confirmed in at least 2 determinations conducted in each interval).

  2. Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102 [ Time Frame: 3 years ]
    During months 6-36 post-infusion, the survival of bone marrow colony forming units to 10nM MMC increases to over or equal to 10% than values determined at 0-2 months post-infusion. (1 determination is considered valid).

  3. Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102 [ Time Frame: 3 years ]
    The level of gene marking of the FANCA-LV provirus in total peripheral blood cells is at least 0.1 vector copy number/nucleated cell during months 6-36 post-infusion. (This should be confirmed in at least 2 determinations conducted at different intervals). An increase in the vector copy number/peripheral blood cell is observed from 0-2 months post-infusion to the 3rd year post-infusion. (This should be confirmed in at least 2 determinations conducted in each interval periods).

  4. 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. During the 3rd year post-infusion, peripheral blood parameters: hemoglobin levels, neutrophils, and platelets will be assessed and considered stable if they remain at over or equal to 80% of values determined at pre-treatment evaluation visit or immediately prior to mobilization before the administration of granulocyte-colony stimulating factor.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Fanconi anemia, as diagnosed by chromosomal fragility assay of cultured T-lymphocytes in the presence of DEB or a similar DNA-crosslinking agent.
  • Subjects of Fanconi Anemia complementation group A.
  • Minimum age: 1 year and a minimum of 8 kg.
  • Maximum age: 12 years.
  • At least one of the following hematologic parameters below lower limits of normal:

    • Hemoglobin
    • Absolute neutrophils
    • Platelets
  • At least 30 CD34+ cells/μL are determined in one BM aspiration within 3 months prior to initiation of CD34+ cell collection.
  • If the number of C34+ cells/ μL in BM is in the range of 10-29, PB parameters should meet two of the three following criteria:

    • Hemoglobin: ≥11g/dL
    • Neutrophils: ≥900 cells/μL
    • Platelets: ≥60,000 cells/μL
  • Provide informed consent in accordance with current legislation.
  • 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:

  • Subjects with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor.
  • Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predictive of these conditions 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.
  • 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 in at least one blood lineage over time must be documented to enable eligibility).
  • Lansky performance status ≤60%.
  • Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study.
  • Pre-existing sensory or motor impairment ≥grade 2 according to the NCI CTCAE v5.0 criteria.
  • Pregnant or breastfeeding women.
  • Hepatic dysfunction as defined by either:

    • Bilirubin >3.0 × upper limit of normal (ULN) or
    • Alanine aminotransferase (ALT) > 5.0 × ULN or
    • Aspartate aminotransferase (AST) > 5.0 × ULN
  • Renal dysfunction requiring either hemodialysis or peritoneal dialysis.
  • Pulmonary dysfunction as defined by either:

    • Need for supplemental oxygen during the prior 2 weeks in absence of acute infection.
    • Oxygen saturation by pulse oximetry <90%.
  • Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years.
  • Subject is receiving androgens (i.e. danazol, oxymethalone).

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 identifier (NCT number): NCT03814408

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United States, California
Stanford University Institute for Stem Cell Biology and Regenerative Medicine Lucille Packard Children's Hospital, Stanford University
Stanford, California, United States, 94304
Sponsors and Collaborators
Rocket Pharmaceuticals Inc.
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Principal Investigator: Sandeep Soni, MD Stanford University, Stem Cell Transplantation and Regenerative Medicine
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Responsible Party: Rocket Pharmaceuticals Inc. Identifier: NCT03814408    
Other Study ID Numbers: RP-L102-0418
First Posted: January 24, 2019    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.:
FANCA, FA-A, Fanconi Anemia Subtype A
Additional relevant MeSH terms:
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Fanconi Syndrome
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