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

• Conditions: Leukocyte Adhesion Deficiency

• Registration Number: NCT06282432
• Lead Sponsor: Rocket Pharmaceuticals Inc.

Brief Summary

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

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 Timeline

• Study Start: 2022-03-09
• Study First Submitted: 2023-11-13
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-20
• Last Update Submitted: 2024-02-20
• Study First Posted: 2024-02-28
• Last Update Posted: 2024-02-28
• Primary Completion: 2037-03
• Study Completion: 2037-03

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 9

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.

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Exclusion Criteria

There are no criteria for exclusion in this study.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Hematopoietic stem cell transplant (HSCT) free survival	15 years	Survival without allogeneic-HSCT.

Secondary Outcome Measures

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

Trial Locations

Locations (3)

University College London Great Ormond Street Institute of Child Health (GOSH); 🇬🇧 London, United Kingdom

University of California, Los Angeles (UCLA); 🇺🇸 Los Angeles, California, United States

Hospital Infantil Universitario Niño Jesús; 🇪🇸 Madrid, Spain