Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A

NCT04069533 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: RP-L102-01182018-002502-31
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 2

Brief Summary

This is an open-label Phase II clinical trial to evaluate the efficacy of a hematopoietic cell-based gene therapy for pediatric 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.

Conditions

Fanconi Anemia Complementation Group A

Keywords

anemia; bone marrow failure; gene therapy

Outcome Measures

Primary Outcomes (1)

• Phenotypic correction of bone marrow colony forming units after infusion of RP-L102

  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).

  3 years

Secondary Outcomes (4)

• Phenotypic correction of T-lymphocytes in peripheral blood 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

  3 years

• Short- and long-term Safety

  3 years

Study Arms (1)

RP-L102

EXPERIMENTAL

RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the 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

RP-L102

Eligibility Criteria

• Age: 1 Year - 17 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 lymphocytes in the presence of diepoxybutane (DEB) or similar DNA-crosslinking agent
• Patient of the complementation group FA-A
• Minimum age: 1 year and minimum weight of 8 kg.
• Maximum age: 17 years
• At least 30 CD34+ cells/µL are determined in one BM aspiration within 3 months prior to the CD34+ cell collection.
• 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:

• Patients with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor
• Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those predictive of these conditions in bone marrow (BM) aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the patient enters the clinical trial
• Patients 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 index ≤ 60%
• Any concomitant disease or condition that, in the opinion of the Principal Investigator, deems the patient unfit to participate in the trial
• Pre-existing sensory or motor impairment \>/= grade 2 according to the criteria of the National Cancer Institute (NCI)
• Pregnant or breastfeeding women
• Hepatic dysfunction as defined by either:
• Bilirubin \> 3 x the upper limit of normal (ULN)
• Alanine aminotransferase (ALT ) \> 5 x 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

Sponsors & Collaborators

• Rocket Pharmaceuticals Inc.: lead

Study Sites (2)

Hospital Infantil Universitario Niño Jesús (HIUNJ)

Madrid, 28009, Spain

Location

University College London Great Ormond Street Institute of Child Health (GOSH)

London, WC1N 1EH, United Kingdom

Location

MeSH Terms

Conditions

Fanconi Syndrome; Anemia; Bone Marrow Failure Disorders

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; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Julián Sevilla Navarro, MD, PhD

  Hospital Infantil Universitario Niño Jesús (HIUNJ)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: August 28, 2019
• Study Start: November 28, 2019
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: May 22, 2024

Record last verified: 2024-05

Locations

GB (1); ES (1)