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

Leukocyte Adhesion Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06282432
• Other study ID #: RP-L201-0121-LTFU
• Status: Enrolling by invitation
• Start date: March 9, 2022
• Est. completion date: March 2037

Study information

• Verified date: February 2024
• Source: Rocket Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 9
• Est. completion date: March 2037
• Est. primary completion date: March 2037
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukocyte Adhesion Deficiency
• Leukocyte-Adhesion Deficiency Syndrome
• Tissue Adhesions

Locations

Country	Name	City	State
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
United Kingdom	University College London Great Ormond Street Institute of Child Health (GOSH)	London
United States	University of California, Los Angeles (UCLA)	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Rocket Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematopoietic stem cell transplant (HSCT) free survival	Survival without allogeneic-HSCT.	15 years
Secondary	Incidence of hospitalizations	Incidence of infection-related hospitalizations.	15 years
Secondary	Incidence of significant infections	Incidence of infections requiring hospitalization or intravenous antimicrobials.	15 years
Secondary	Resolution of LAD-I-related skin rash	Partial or complete resolution of LAD-I skin rash evident by photographical images.	15 years
Secondary	Resolution of LAD-I-related periodontal abnormalities	Partial or complete resolution of LAD-I periodontal abnormalities evident by photographical images.	15 years
Secondary	Event free survival	Survival in the absence of graft failure and graft versus host disease.	15 years
Secondary	Overall Survival	Survival in the absence of death from any cause	15 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Long-term CD11 neutrophil expression by flow cytometry	Persistence of CD11 a/b neutrophil co-expression	15 Years
Secondary	Improvement or resolution of LAD-I related neutrophilia	Improvement of LAD-I related neutrophilia based off neutrophils within age-appropriate normal ranges.	15 Years
Secondary	Improvement or resolution of LAD-I-related leukocytosis.	Improvement of LAD-I related leukocytosis based off leukocytes within age-appropriate normal ranges.	15 Years
Secondary	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
Secondary	Incidence of hematologic malignancy	Incidence of hematologic malignancy related to prior gene therapy or gene-therapy associated medications.	15 Years