Adenosine Deaminase DeficiencyNCT04049084
An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
An observational study of Adenosine Deaminase Deficiency and Severe Combined Immunodeficiency (SCID), run by University of California, Los Angeles at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Adenosine Deaminase Deficiency, Severe Combined Immunodeficiency (SCID)
- What is being tested?
- autologous ex vivo gene therapy products based on the EFS LV encoding for the human adenosine deaminase (ADA) gene (EFS-ADA LV)
- How many people
- 70 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 26 Sep 2019to Aug 2040
- How long will I take part?
- 13 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- A patient is eligible for enrollment in the study if all of the following criteria are met:
- 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;
- the patient displays persistent detectable gene marking, as determined by the Investigator;
- the patient or, if applicable, the patient's parent(s)/legal guardian(s), are able and willing to provide informed consent.
Who cannot join
- There are no exclusion criteria for participation in this observational LTFU study.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site
Mattel Children's Hospital UCLA/Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
United Kingdom1 site
UCL Great Ormond Street Institute of Child Health
London, WC1N 1EH
About this study
Official title: 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.
Read the 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
- Being tested
- autologous ex vivo gene therapy products based on the EFS LV encoding for the human adenosine deaminase (ADA) gene (EFS-ADA LV)
- Keywords
- OTL-101
- Medical subject headings
- Severe combined immunodeficiency due to adenosine deaminase deficiency, Severe Combined Immunodeficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous ex vivo gene therapy products based on the EFS LV encoding for the human adenosine deaminase (ADA) gene (EFS-ADA LV)Biological
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)
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Establishing efficacy through overall survival
Measured: 15 years post-treatment
Event-Free Survival
Establishing efficacy through event-free survival
Measured: 15 years post-treatment
Incidence of Adverse Events
Long-Term Safety incidence of AEs and SAEs
Measured: 15 years post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2019
- Study start26 Sep 2019
- Primary completionAug 2040 (estimated)
- Study completionAug 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adenosine Deaminase DeficiencyStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 70 participants (estimated)
- Target duration
- 13 Years
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Responsible party
- Principal investigator, Donald B. Kohn, M.D., University of California, Los Angeles
- Investigators
- Donald B. Kohn, M.D., Study director, University of Califorina, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04049084
- Sponsor's protocol ID
- OTL-101-6
- Status last verified
- Dec 2025
- First submitted
- 6 Aug 2019
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 41092330
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04049084
- Acronym / sponsor ID
- OTL-101-6
- Keywords
- OTL-101
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- Aug 2040 (estimated)
- Study completion
- Aug 2040 (estimated)
- First posted
- 7 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Other
- Time perspective
- Other
- Target follow-up
- 13 Years
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- A patient is eligible for enrollment in the study if all of the following criteria are met:
- 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;
- the patient displays persistent detectable gene marking, as determined by the Investigator;
- the patient or, if applicable, the patient's parent(s)/legal guardian(s), are able and willing to provide informed consent.
Key exclusion criteria (1 listed)
- There are no exclusion criteria for participation in this observational LTFU study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) | Biological | – |
Primary outcome
Overall Survival
Time frame: 15 years post-treatment
Establishing efficacy through overall survival
Event-Free Survival
Time frame: 15 years post-treatment
Establishing efficacy through event-free survival
Incidence of Adverse Events
Time frame: 15 years post-treatment
Long-Term Safety incidence of AEs and SAEs
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Derived from this study: PubMed 41092330Booth 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.
- Individual participant dataSharing planned: No
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Gene Therapy for Adenosine Deaminase Severe Combined Immune Deficiency Using Peripheral Blood and EFS ADA Vector
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Donald B. Kohn, M.D. study director
University of Califorina, Los Angeles
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adenosine Deaminase Deficiency and Severe Combined Immunodeficiency (SCID), run by University of California, Los Angeles at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 15 years post-treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04049084, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.