An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID

NCT ID: NCT04049084

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-09-26
• Study Completion Date: 2040-08-31

Brief Summary

This observational long-term follow-up study is designed to collect safety and efficacy data from ADA-SCID patients previously treated with autologous ex vivo gene therapy products based on the EFS-ADA LV encoding for human adenosine deaminase (ADA) gene (EFS-ADA LV), as part of the OTL-101 clinical development program. No investigational medicinal product will be administered to these patients as part of the OTL-101-6 study.

Detailed Description

The overall aim of this study is to record and evaluate long-term safety and efficacy data from ADA-SCID patients previously treated with autologous ex vivo gene therapy products based on the EFS-ADA vector, as part of the UCL/A- ADA clinical development program. This will fulfil the requirements for the monitoring of delayed adverse events set by regulatory agencies for subjects treated with gene therapies.

The study will have the following specific objectives:

• To characterize the long-term safety of the gene therapy treatment;
• To characterize the long-term clinical efficacy of the gene therapy treatment. Patients who were treated as part of the UCL/A-ADA clinical development program but did not complete the expected follow- up period (e.g. as a consequence of early withdrawal due to safety events) will be included in the LTFU study, subject to their consent and compliance with inclusion and exclusion criteria.

For any patients who completed their expected follow-up period before this study became available, outcome data will be retrospectively collected for the intervening period. From the first LTFU assessment onwards, prospective data will be gathered from the annual standard of care evaluations the patients will receive from the PI or their local healthcare professionals (HCPs).

Each patient, or their legal guardian, will be required to provide informed consent, which will define the objectives of this study, the expected duration of the patient's participation, as well as the data to be collected and the schedule of collection. It is anticipated that data will be collected annually to coincide with standard of care visits.

The study outcomes will be:

• Overall survival (OS) at 15 years of follow-up post treatment with gene therapy;
• Event-free survival (EvFS) at 15 years of follow-up post treatment with gene therapy. An "event" will be defined as enzyme replacement therapy (ERT) reinstitution, need for a rescue allogeneic hematopoietic stem cell transplant (HSCT) or further gene therapy treatment;
• Use of immunoglobulin replacement therapy (IgRT);
• Adverse events (AEs), serious adverse events (SAEs) and safety concerns
• Other physical and laboratory parameters

Conditions

Adenosine Deaminase Deficiency; Severe Combined Immunodeficiency (SCID)

Keywords

OTL-101

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: OTHER

Interventions

autologous ex vivo gene therapy products based on the EFS LV encoding for the human adenosine deaminase (ADA) gene (EFS-ADA LV)

ADA-SCID patients previously treated with autologous ex vivo gene therapy products based on the EFS LV encoding for the human adenosine deaminase (ADA) gene (EFS-ADA LV)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

A patient is eligible for enrollment in the study if all of the following criteria are met:

1. the patient has been treated with an autologous ex vivo gene therapy product based on the EFS-ADA LV, as part of the OTL-101 clinical development program;

2. the patient displays persistent detectable gene marking, as determined by the Investigator;

3. the patient or, if applicable, the patient's parent(s)/legal guardian(s), are able and willing to provide informed consent.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Donald B. Kohn, M.D.

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Donald B. Kohn, M.D.

Role: STUDY_DIRECTOR

University of Califorina, Los Angeles

Locations

Mattel Children's Hospital UCLA/Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

UCL Great Ormond Street Institute of Child Health

London, , United Kingdom

Countries

United States; United Kingdom

References

Booth C, Masiuk K, Vazouras K, Fernandes A, Xu-Bayford J, Campo Fernandez B, Roy S, Curio-Penny B, Arnold J, Terrazas D, Reid J, Gilmour KC, Adams S, Alvarez Mediavilla E, Mhaldien L, O'Toole G, Ahmed R, Garabedian E, Malech H, De Ravin SS, Moore TB, De Oliveira S, Pellin D, Lin TY, Dang TT, Cornetta K, Hershfield MS, Hara H, Thrasher AJ, Gaspar HB, Kohn DB. Long-Term Safety and Efficacy of Gene Therapy for Adenosine Deaminase Deficiency. N Engl J Med. 2025 Oct 16;393(15):1486-1497. doi: 10.1056/NEJMoa2502754.

Reference Type: DERIVED

PMID: 41092330 (View on PubMed)

Other Identifiers

OTL-101-6

Identifier Type: -

Identifier Source: org_study_id