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

An Observational Long-term Follow-up Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Adenosine Deaminase Deficiency; Severe Combined Immunodeficiency (SCID)
• Intervention / Treatment: Biological: autologous ex vivo gene therapy products based on the EFS LV encoding for the human adenosine deaminase (ADA) gene (EFS-ADA LV)

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

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • UCL Great Ormond Street Institute of Child Health
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Mattel Children's Hospital UCLA/Ronald Reagan UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This observational LTFU study is open for enrollment to ADA-SCID patients previously treated with autologous ex vivo gene therapy products based on the EFS-ADA lentiviral vector as part of the OTL-101 clinical development program. Patients treated in clinical trials as part of IND #15440, study OTL-101-5 (EudraCT No 2017-001275-23) or study 10-MI-29 (EudraCT No 2010-024253-36), as well as in Expanded Access or Compassionate Use Programs, will be eligible for enrollment.

Description

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.

Exclusion Criteria:

• There are no exclusion criteria for participation in this observational LTFU study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Establishing efficacy through overall survival	15 years post-treatment
Event-Free Survival	Establishing efficacy through event-free survival	15 years post-treatment
Incidence of Adverse Events	Long-Term Safety incidence of AEs and SAEs	15 years post-treatment

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Great Ormond Street Hospital for Children NHS Foundation Trust
• Investigators: Study Director: Donald B. Kohn, M.D., University of Califorina, Los Angeles

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Estimated): August 1, 2040
• Study Completion (Estimated): August 1, 2040

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Estimated): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: OTL-101
• Additional Relevant MeSH Terms: Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Immune System Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; DNA Repair-Deficiency Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Severe Combined Immunodeficiency; Severe combined immunodeficiency due to adenosine deaminase deficiency; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Genes
• Other Study ID Numbers: OTL-101-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No