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

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT06282432

Enrollment

Registered

2024-02-28

Start date

2022-03-09

Completion date

2036-10-04

Last updated

2025-12-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukocyte Adhesion Deficiency

Keywords

LAD-I, LAD

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.

Interventions

None listed

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

3 Months to No maximum

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
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.
Resolution of LAD-I-related periodontal abnormalities	15 years	Partial or complete resolution of LAD-I periodontal abnormalities evident by photographical images.
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 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.
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
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.
Incidence of hematologic malignancy	15 Years	Incidence of hematologic malignancy related to prior gene therapy or gene-therapy associated medications.
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.

Countries

Spain, United Kingdom, United States

Outcome results