Clinical trial NCT06282432: Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I)
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
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Leukocyte Adhesion Deficiency
Keywords: LAD-I
LAD
Lead sponsor: Rocket Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 9
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects that have been treated with RP-L201 on the RP-L201-0318 study.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hematopoietic stem cell transplant (HSCT) free survival
timeFrame: 15 years
Secondary outcomes:
measure: Incidence of hospitalizations
timeFrame: 15 years
measure: Incidence of significant infections
timeFrame: 15 years
measure: Resolution of LAD-I-related skin rash
timeFrame: 15 years
measure: Resolution of LAD-I-related periodontal abnormalities
timeFrame: 15 years
measure: Event free survival
timeFrame: 15 years
measure: Overall Survival
timeFrame: 15 years
measure: Long-term genetic correction in peripheral blood mononuclear cells (PBMCs)
timeFrame: 15 years
measure: Long-term genetic correction in PB CD15+ granulocytes
timeFrame: 15 years
measure: Long-term CD18 neutrophil expression by flow cytometry
timeFrame: 15 Years
measure: Long-term CD11 neutrophil expression by flow cytometry
timeFrame: 15 Years
measure: Improvement or resolution of LAD-I related neutrophilia
timeFrame: 15 Years
measure: Improvement or resolution of LAD-I-related leukocytosis.
timeFrame: 15 Years
measure: Incidence of Investigational Product (IP) related serious adverse events (SAEs)
timeFrame: 15 Years
measure: Incidence of hematologic malignancy
timeFrame: 15 Years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
city: London
country: United Kingdom
facility: University College London Great Ormond Street Institute of Child Health (GOSH)
Study officials:
affiliation: University of California, Los Angeles
name: Donald Kohn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University College London Great Ormond Street Institute of Child Health
name: Claire Booth, MBBS, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Infantil Universitario Niño Jesús
name: Julian Sevilla, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: