A Clinical Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I

NCT03812263 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: RP-L201-0318
• Study Type: interventional
• Target: 9
• Locations: 3 countries
• Sites: 3

Brief Summary

The primary purpose of the Phase I portion of the 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 the therapeutic lentiviral vector, Chim-CD18-WPRE, RP-L201. The primary objectives of the Phase II portion of the study are evaluation of survival, as determined by the proportion of subjects alive at age 2 (24 months) and at least 1-year post-infusion without allogeneic hematopoietic stem cell transplant (HSCT) and characterization of the safety and toxicity associated with the infusion.

Conditions

Leukocyte Adhesion Defect - Type I

Keywords

Leukocyte Adhesion Deficiency- Type I; LAD-I; ITGB2 mutation; CD18 deficiency

Outcome Measures

Primary Outcomes (3)

• Phase I: Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0

  Evaluation of safety associated with treatment with RP-L201

  2 years

• Phase II: Survival following infusion of RP-L201

  , as determined by the proportion of subjects alive at least 1-year post investigational product infusion without allogeneic HSCT and alive at age 2 (24 months) without allogeneic HSCT for subjects less than 1 year of age at study enrollment.

  2 years

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

  Evaluation of safety associated with treatment with RP-L201

  2 years

Secondary Outcomes (7)

• CD18 expression after infusion of RP-L201

  2 years

• Genetic correction after infusion of RP-L201

  2 years

• Incidence of infections after infusion of RP-L201

  2 years

• Assessment of LAD-I-associated neutrophilia after infusion of RP-L201

  2 years

• Assessment of LAD-I-associated leukocytosis after infusion of RP-L201

  2 years

Study Arms (1)

RP-L201

EXPERIMENTAL

RP-L201 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with Chim-CD18-WPRE lentiviral vector administered as a single intravenous infusion

Biological: RP-L201

Interventions

RP-L201 BIOLOGICAL

CD34+ enriched hematopoietic stem cells from subjects with severe LAD-I transduced ex vivo with lentiviral vector carrying the ITGB2 gene, Chim-CD18-WPRE.

RP-L201

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating CD18 expression on \<2% neutrophils (polymorphonuclear neutrophils (PMNs)). Subjects in which CD18+ PMNs are \>2% will be considered eligible with \<2% CD11a or CD11b expressing PMNs and if there is a documented ITGB2 mutation and clinical history consistent with LAD-I (or known family history).
• Age ≥3 months.
• Considered to be an appropriate candidate for autologous transplantation of hematopoietic stem cells.
• A competent custodial parent with legal capacity to execute an institutional review board (IRB)/ethics committee (EC)-approved consent form must be available to participate in the consent process. (Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/EC and with local requirements).
• Ability to comply with trial procedures including investigational therapy and follow-up evaluations.

You may not qualify if:

• Hepatic dysfunction as defined by either:
• Bilirubin \>1.5× the upper limit of normal (ULN) or
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5×ULN.
• Renal dysfunction as defined by either Grade 3 or higher abnormalities in serum sodium, potassium, calcium, magnesium or phosphate as defined by NCI CTCAE v5.0, or the requirement for either peritoneal dialysis or hemodialysis.
• 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 (including hematologic malignancy) for which survival is anticipated to be less than 3 years.
• Serious infections with persistent bloodstream pathogens at time of trial entry. (Subjects with active infections (e.g., unresolved ulcerative lesions, skin or oral infections) are permitted as long as appropriate antibiotic therapy has been (or is being) administered).
• Any medical or other contraindication for both leukapheresis and bone marrow harvest procedure, as determined by the treating Investigator.
• Any medical or other contraindication for the administration of conditioning therapy, as determined by the treating Investigator.
• Significant medical conditions, including documented human immunodeficiency virus (HIV) infection, poorly-controlled diabetes, poorly-controlled hypertension, poorly-controlled cardiac arrhythmia or congestive heart failure; or arterial thromboembolic events (including stroke or myocardial infarction) within the 6 prior months.
• Any medical or psychiatric condition that in the opinion of the Investigator renders the subject unfit for trial participation or at higher than acceptable risk for participation.

Sponsors & Collaborators

• Rocket Pharmaceuticals Inc.: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (3)

University of California, Los Angeles

Los Angeles, California, 90095-1489, United States

Location

Hospital Infantil Universitario Niño Jesús (HIUNJ)

Madrid, 28009, Spain

Location

University College London Great Ormond Street Institute of Child Health

London, United Kingdom

Location

Related Publications (1)

• Booth C, Sevilla J, Almarza E, Kuo CY, Zubicaray J, Terrazas D, O'Toole G, Chitty-Lopez M, Choi G, Nicoletti E, Long-Boyle J, Fernandes A, Chetty K, De Oliveira S, Banuelos C, Xu-Bayford J, Bastone AL, John-Neek P, Jackson C, Moore TB, Gilmour K, Schambach A, Rothe M, Kasbekar S, Rao GR, Patel K, Shah G, Thrasher AJ, Bueren JA, Schwartz JD, Kohn DB. Lentiviral Gene Therapy for Severe Leukocyte Adhesion Deficiency Type 1. N Engl J Med. 2025 May 1;392(17):1698-1709. doi: 10.1056/NEJMoa2407376.

  PMID: 40305711 DERIVED

MeSH Terms

Conditions

Leukocyte adhesion deficiency type 1

Study Officials

• Donald B Kohn, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Claire Booth, MBBS, PhD, MSc

  University College London Great Ormond Street Institute of Child Health

  PRINCIPAL INVESTIGATOR

• Julián Sevilla Navarro, MD, PhD

  Hospital Infantil Universitario Niño Jesús

  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 18, 2019
• First Posted: January 23, 2019
• Study Start: August 30, 2019
• Primary Completion: September 12, 2023
• Study Completion: September 12, 2023
• Last Updated: November 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); US (1); GB (1)