A Clinical Trial to Evaluate the Safety of RP-L102 in Pediatric Subjects With Fanconi Anemia Subtype A

NCT03814408 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: RP-L102-0418
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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).

Conditions

Fanconi Anemia Complementation Group A

Keywords

FANCA, FA-A, Fanconi Anemia Subtype A

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0

  Evaluation of safety associated with treatment with RP-L102

  3 years

Secondary Outcomes (4)

• Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102

  3 years

• Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102

  3 years

• Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102

  3 years

• Prevention or rescue of bone marrow failure after infusion of RP-L102

  3 years

Study Arms (1)

RP-L102

EXPERIMENTAL

RP-L102 is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene

Biological: RP-L102

Interventions

RP-L102 BIOLOGICAL

CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE

RP-L102

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Rocket Pharmaceuticals Inc.: lead

Study Sites (1)

Stanford University Institute for Stem Cell Biology and Regenerative Medicine Lucille Packard Children's Hospital, Stanford University

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Fanconi Syndrome

Condition Hierarchy (Ancestors)

Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Agnieszka Czechowicz, MD

  Stanford University, Stem Cell Transplantation and Regenerative Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 24, 2019
• Study Start: January 11, 2019
• Primary Completion: December 1, 2020
• Study Completion: March 1, 2022
• Last Updated: November 24, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)