Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I)

Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I) Phase I/II Clinical Study to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector Encoding the ITGB2 Gene

This Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I) is a continuation of a Phase 1/2 clinical study to evaluate the safety and efficacy of the infusion of autologous hematopoietic stem cells transduced with a lentiviral vector encoding the ITGB2 gene

Study Overview

• Status: Enrolling by invitation
• Conditions: Leukocyte Adhesion Deficiency

Detailed Description

Following the end of participation in Study RP-L201-0318, patients will be offered enrollment into this LTFU protocol. Patients will be followed for up to 15 years following the RP-L201 infusion in the parent study, until the patient dies, withdraws consent, or is lost to follow-up (whichever occurs first).

For all follow-up visits, remote evaluation facilitated by local health care providers (with blood sample shipment to relevant laboratory facilities) is permitted; however, annual visits to the study center are required during initial 3 years post- RP-L201 infusion. Visits where a bone marrow sample is being collected are required to be performed at the study center for the duration of the study. Peripheral Blood samples and bone marrow samples will be archived and tested when clinically or scientifically indicated, as in the event of development of a second malignancy.

• Study Type: Observational
• Enrollment (Estimated): 9

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus
• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • University College London Great Ormond Street Institute of Child Health (GOSH)
• United States
  • California
    • Los Angeles, California, United States, 90095-1489
      • University of California, Los Angeles (UCLA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects that have been treated with RP-L201 on the RP-L201-0318 study.

Description

Inclusion Criteria:

1. Enrolled in the Phase I/II Study RP-L201-0318.
2. Received an autologous infusion of CD34+ hematopoietic stem cells modified with a lentiviral vector containing the ITGB2 gene, encoding for the human CD18 receptor in the parent Study RP-L201-0318.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Provided written informed consent and, as applicable, assent to participate in the current study.

Exclusion Criteria:

There are no criteria for exclusion in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Subjects that received RP-L201 on the RP-L201-0318 Parent Study; Subjects that received RP-L201 on the RP-L201-0318 Parent Study and either completed the study or discontinued early.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematopoietic stem cell transplant (HSCT) free survival	Survival without allogeneic-HSCT.	15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hospitalizations	Incidence of infection-related hospitalizations.	15 years
Incidence of significant infections	Incidence of infections requiring hospitalization or intravenous antimicrobials.	15 years
Resolution of LAD-I-related skin rash	Partial or complete resolution of LAD-I skin rash evident by photographical images.	15 years
Resolution of LAD-I-related periodontal abnormalities	Partial or complete resolution of LAD-I periodontal abnormalities evident by photographical images.	15 years
Event free survival	Survival in the absence of graft failure and graft versus host disease.	15 years
Overall Survival	Survival in the absence of death from any cause	15 years
Long-term genetic correction in peripheral blood mononuclear cells (PBMCs)	Persistence of transgene in PB cells as demonstrated by vector copy number (VCN) of at least 0.1 in PBMCs.	15 years
Long-term genetic correction in PB CD15+ granulocytes	Persistence of transgene in PB cells as demonstrated by VCN of at least 0.1 in PB CD15+ granulocytes.	15 years
Long-term CD18 neutrophil expression by flow cytometry	Persistence of CD18 neutrophil expression defined by PB neutrophil CD18 expression to at least 10% of normal.	15 Years
Long-term CD11 neutrophil expression by flow cytometry	Persistence of CD11 a/b neutrophil co-expression	15 Years
Improvement or resolution of LAD-I related neutrophilia	Improvement of LAD-I related neutrophilia based off neutrophils within age-appropriate normal ranges.	15 Years
Improvement or resolution of LAD-I-related leukocytosis.	Improvement of LAD-I related leukocytosis based off leukocytes within age-appropriate normal ranges.	15 Years
Incidence of Investigational Product (IP) related serious adverse events (SAEs)	Incidence of SAEs related to the IP measured by CTCAE (Common Terminology Criteria for Adverse Events) for V5.0 grading scale.	15 Years
Incidence of hematologic malignancy	Incidence of hematologic malignancy related to prior gene therapy or gene-therapy associated medications.	15 Years

Collaborators and Investigators

• Sponsor: Rocket Pharmaceuticals Inc.
• Investigators: Principal Investigator: Claire Booth, MBBS, PhD, MSc, University College London Great Ormond Street Institute of Child Health; Principal Investigator: Donald Kohn, MD, University of California, Los Angeles; Principal Investigator: Julian Sevilla, MD, PhD, Hospital Infantil Universitario Nino Jesus

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2022
• Primary Completion (Estimated): March 1, 2037
• Study Completion (Estimated): March 1, 2037

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: LAD; LAD-I
• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Genetic Diseases, Inborn; Fibrosis; Cicatrix; Primary Immunodeficiency Diseases; Tissue Adhesions; Leukocyte-Adhesion Deficiency Syndrome
• Other Study ID Numbers: RP-L201-0121-LTFU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No