ADA-SCIDPhase 1/2NCT01852071
Autologous CD34+ Hematopoietic Stem Cells Transduced ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for the Human ADA Gene
A Phase 1/2 study testing Infusion of autologous EFS-ADA LV CD34+ (OTL-101), busulfan and PEG-ADA ERT in people with ADA-SCID, run by University of California, Los Angeles at 2 sites in United States.
Trial summary
The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from the bone marrow (BM) of ADA-deficient SCID infants and children following human ADA cDNA transfer by the EFS-ADA lentiviral vector. Read more about this study
- Who is it for?
- Ages 1 month to 17 years
- Conditions the study is for
- ADA-SCID
- What is being tested?
- Infusion of autologous EFS-ADA LV CD34+ (OTL-101), busulfan and PEG-ADA ERT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Aug 2013to 27 Aug 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 month to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- -Children ≥ 1.0 months of age with a diagnosis of ADA-deficient SCID based on A. Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured fetal cells to levels consistent with ADA-deficient SCID as determined by reference laboratory or confirmed ADA gene mutation(s) known to cause disease , AND
- Evidence of severe combined immunodeficiency based on either:
- Family history of first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency, OR
- Evidence of severe immunologic deficiency in subject prior to institution of immune restorative therapy, based on
- lymphopenia (absolute lymphocyte count <400 cells/mcL) OR absence or low number of T cells (absolute CD3+ count <300 cells/mcL) OR
- severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (either <10% of lower limit of normal controls for the diagnostic laboratory, <10% of the response of the normal control of the day, or stimulation index <10)
- Ineligible for matched sibling allogeneic bone marrow transplantation: absence of a medically eligible HLA-identical sibling, with normal immune function, who may serve as an allogeneic bone marrow donor
- Signed written informed consent according to guidelines of the Institutional Review Board (IRB) (UCLA Office of Human Research Protection Program and National Human Genome Research Institute (NHGRI) IRB
Who cannot join
- Age ≤ 1.0 months Appropriate organ function as outlined below must be observed within 60 days of entering this trial.
- Hematologic
- Anemia (hemoglobin < 10.5 g/dl at < 2 years of age, or < 11.5 g/dl at > 2 years of age).
- Neutropenia (absolute granulocyte count <500/mm3.
- Thrombocytopenia (platelet count < 150,000/mm3, at any age).
- International Normalised Ratio (INR) or Prothrombin Time (PT) > 2 times the upper limits of normal or Partial Thromboplastin Time (PTT) > 2.33 times the upper limit of normal (patients with a correctable deficiency controlled on medication will not be excluded).
Show all 40Show fewer
- Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid (if available).
- Prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) with cytoreductive conditioning
- Infectious
- Evidence of infection with HIV-1, hepatitis B, Hepatitis C, or parvovirus B 19 by DNA Polymerase Chain Reaction (PCR) within 90 days prior to bone marrow harvest. If other infection is present, it must be under control (e.g. stable or decreasing viral load) at the time of screening
- Pulmonary
- Resting O2 saturation by pulse oximetry < 95% on room air.
- Chest x-ray indicating active or progressive pulmonary disease.
- Cardiac
- Abnormal electrocardiogram (EKG) indicating cardiac pathology.
- Uncorrected congenital cardiac malformation with clinical symptomatology.
- Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension.
- Poor cardiac function as evidenced by LV ejection fraction < 40% on echocardiogram.
- Neurologic
- Significant neurologic abnormality by examination.
- Uncontrolled seizure disorder.
- Renal
- Renal insufficiency: serum creatinine >= 1.2 mg/dl, or >= 3+ proteinuria.
- Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III or IV by Division of AIDS Toxicity Scale.
- Hepatic/GI:
- Serum transaminases > 5 times the upper limit of normal (ULN).
- Serum bilirubin > 2 times ULN.
- Serum glucose > 1.5 times ULN.
- Intractable severe diarrhea.
- Oncologic
- Evidence of active malignant disease other than dermatofibrosarcoma protuberans (DFSP)
- Evidence of DFSP expected to require anti-neoplastic therapy within the 5 years following the infusion of genetically corrected cells
- Evidence of DFSP expected to be life limiting within the 5 years following the infusion of genetically corrected cells
- Known sensitivity to Busulfan
- General
- Expected survival < 6 months.
- Pregnant.
- Major congenital anomaly.
- Ineligible for autologous HSCT by the criteria at the clinical site.
- Other conditions which in the opinion of the principal investigator and/or co-investigators, contra-indicate the bone marrow harvest, the administration of busulfan, infusion of transduced cells or indicate the patient or patient's parents/primary caregivers inability to follow protocol.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mark O. Hatfield Clinical Research Center, NIH
Bethesda, Maryland, 20892
Mattel Children's Hospital, UCLA
Los Angeles, California, 90095
About this study
Official title: Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA Complementary DNA (cDNA) by the EFS-ADA Lentiviral Vector for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)
The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from the bone marrow (BM) of ADA-deficient SCID infants and children following human ADA cDNA transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.
Read the detailed description
The study is open to twenty (20) infants and children diagnosed with ADA-deficient SCID who did not have a medically eligible, human leukocyte antigen (HLA)-identical sibling donor for bone marrow transplantation. The EFS-ADA lentiviral vector with the human ADA cDNA will be used to transduce autologous CD34+ cells from the bone marrow of these subjects. The subjects will receive 4 mg/kg busulfan prior to re-infusion of their gene-modified cells. Safety is the primary endpoint. During the follow-up phase, the investigators aim to determine whether the cells could engraft and produce mature cells that contain and express the corrected ADA gene in the absence of pegademase bovine (PEG-ADA) enzyme replacement therapy (ERT), which will be withheld at Day +30 following transplant. Efficacy studies to evaluate the level of immune reconstitution, will be performed in the first and second years of the study.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of autologous EFS-ADA LV CD34+ (OTL-101)Genetic
Also called OTL-101
autologous EFS-ADA LV CD34+ cells (OTL-101) are infused intravenously
busulfanDrug
Busulfan is used for non-myeloablative conditioning
PEG-ADA ERTDrug
PEG-ADA ERT is discontinued at Day +30 (-3/+15 days) after successful engraftment
| Study group | Role | What they receive |
|---|---|---|
| Gene Therapy | Experimental | Infusion of autologous EFS-ADA Lentiviral (LV) CD34+ cells Receives: Genetic: Infusion of autologous EFS-ADA LV CD34+ (OTL-101); Drug: busulfan; Drug: PEG-ADA ERT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101 or HSCT
Measured: 12 months
Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Event-free survival is defined as the percentage of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death.
Measured: 12 months
Secondary outcomes (9)
OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
OS is defined as the percentage of subjects alive at 24 months post- treatment with OTL-101 or HSCT
Measured: 24 months
EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
Event-free survival is defined as the percentage of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.
Measured: 24 months
Vector Copy Number (VCN) in Peripheral Blood (PB) Granulocytes.
Vector copy number in the PB granulocyte fraction that was T cell depleted, is a surrogate for amount of engrafted genetically modified Hematopoietic stem cell (HSC) that are producing granulocytes every 3-5 days. VCN analysis was performed by Droplet Digital PCR (ddPCR) on DNA extracted from peripheral blood granulocytes.
Measured: 24 months
VCN in Peripheral Blood Mononuclear Cells (PBMCs)
PBMC VCN is a measure of the accumulation of peripheral blood leukocytes arising from engrafted, genetically modified HSC. VCN analysis was performed by ddPCR on DNA extracted from PBMC.
Measured: 24 months
ADA Activity in Erythrocytes
ADA enzyme activity measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV; persistence of ADA enzyme activity over time demonstrates successful engraftment and differentiation of genetically modified HSC.
Measured: 24 months
Reduction in Deoxyadenosine Nucleotide (dAXP) in Erythrocytes
Decreased dAXP levels coincide with increased ADA enzyme activity, detoxification was used to demonstrate functional ADA enzyme production from the introduced ADA transgene. The threshold for detoxification was <100 μmol/L.
Measured: 24 months
Change From Baseline in CD3+ T Cell Counts (2 Years)
Immune reconstitution was assessed by change in CD3+ T Cell counts at baseline to Month 24.
Measured: 24 months
Number of Single Integration Sites Representing >30% of the Total Integration Sites (2 Years)
Vector Integration Site Analysis (VISA) allowed determination of the distribution of vector integration sites in each subject's genome, as well as the relative clonal abundance. VISA was to be considered abnormal for a subject if, in 2 or more instances during the course of follow-up, a single integration site was found to represent >30% of the total integration sites detected.
Measured: 24 months
Severe Infection Rate Excluding the First Three Months After Treatment
The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. Infections that took place in the first 3 months of follow-up post treatment were excluded from calculations to avoid possible bias introduced in the data by the effects of conditioning.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2013 (estimated)
- Study start2 Aug 2013
- Primary completion27 Aug 2018
- Study completion27 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ADA-SCIDStudies 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Heart, Lung, and Blood Institute (NHLBI), Orchard Therapeutics
- Responsible party
- Principal investigator, Donald B. Kohn, M.D., University of California, Los Angeles
- Investigators
- Donald B Kohn, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01852071
- Sponsor's protocol ID
- EFS-ADA
- Other IDs
- U01AI100801, 2P01HL073104, 0910-1006
- Status last verified
- Aug 2022
- First submitted
- 7 May 2013
- Last updated
- 3 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Publications
Candotti F, Shaw KL, Muul L, Carbonaro D, Sokolic R, Choi C, Schurman SH, Garabedian E, Kesserwan C, Jagadeesh GJ, Fu PY, Gschweng E, Cooper A, Tisdale JF, Weinberg KI, Crooks GM, Kapoor N, Shah A, Abdel-Azim H, Yu XJ, Smogorzewska M, Wayne AS, Rosenblatt HM, Davis CM, Hanson C, Rishi RG, Wang X, Gjertson D, Yang OO, Balamurugan A, Bauer G, Ireland JA, Engel BC, Podsakoff GM, Hershfield MS, Blaese RM, Parkman R, Kohn DB. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Blood. 2012 Nov 1;120(18):3635-46. doi: 10.1182/blood-2012-02-400937. Epub 2012 Sep 11.
PubMed 22968453Carbonaro DA, Zhang L, Jin X, Montiel-Equihua C, Geiger S, Carmo M, Cooper A, Fairbanks L, Kaufman ML, Sebire NJ, Hollis RP, Blundell MP, Senadheera S, Fu PY, Sahaghian A, Chan RY, Wang X, Cornetta K, Thrasher AJ, Kohn DB, Gaspar HB. Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Mol Ther. 2014 Mar;22(3):607-622. doi: 10.1038/mt.2013.265. Epub 2013 Nov 20.
PubMed 24256635Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, Carbonaro-Sarracino DA, Soni K, Terrazas D, Snell K, Ikeda A, Leon-Rico D, Moore TB, Buckland KF, Shah AJ, Gilmour KC, De Oliveira S, Rivat C, Crooks GM, Izotova N, Tse J, Adams S, Shupien S, Ricketts H, Davila A, Uzowuru C, Icreverzi A, Barman P, Campo Fernandez B, Hollis RP, Coronel M, Yu A, Chun KM, Casas CE, Zhang R, Arduini S, Lynn F, Kudari M, Spezzi A, Zahn M, Heimke R, Labik I, Parrott R, Buckley RH, Reeves L, Cornetta K, Sokolic R, Hershfield M, Schmidt M, Candotti F, Malech HL, Thrasher AJ, Gaspar HB. Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency. N Engl J Med. 2021 May 27;384(21):2002-2013. doi: 10.1056/NEJMoa2027675. Epub 2021 May 11.
PubMed 33974366
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA Complementary DNA (cDNA) by the EFS-ADA Lentiviral Vector for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)
- ClinicalTrials.gov ID
- NCT01852071
- Acronym / sponsor ID
- EFS-ADA
- Conditions
- ADA-SCID
- Keywords
- gene therapy, hematopoietic stem cell, ADA-SCID, lentiviral vector
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Heart, Lung, and Blood Institute (NHLBI), Orchard Therapeutics
- Study start
- 2 Aug 2013 (actual)
- Primary completion
- 27 Aug 2018 (actual)
- Study completion
- 27 Aug 2018 (actual)
- First posted
- 13 May 2013 (estimated)
- Results
- Posted 20 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from the bone marrow (BM) of ADA-deficient SCID infants and children following human ADA cDNA transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.
Detailed description
The study is open to twenty (20) infants and children diagnosed with ADA-deficient SCID who did not have a medically eligible, human leukocyte antigen (HLA)-identical sibling donor for bone marrow transplantation. The EFS-ADA lentiviral vector with the human ADA cDNA will be used to transduce autologous CD34+ cells from the bone marrow of these subjects. The subjects will receive 4 mg/kg busulfan prior to re-infusion of their gene-modified cells. Safety is the primary endpoint. During the follow-up phase, the investigators aim to determine whether the cells could engraft and produce mature cells that contain and express the corrected ADA gene in the absence of pegademase bovine (PEG-ADA) enzyme replacement therapy (ERT), which will be withheld at Day +30 following transplant. Efficacy studies to evaluate the level of immune reconstitution, will be performed in the first and second years of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gene Therapy | Experimental | Genetic: Infusion of autologous EFS-ADA LV CD34+ (OTL-101), Drug: busulfan, Drug: PEG-ADA ERTInfusion of autologous EFS-ADA Lentiviral (LV) CD34+ cells |
Who may qualify
- Ages
- 1 month to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- -Children ≥ 1.0 months of age with a diagnosis of ADA-deficient SCID based on A. Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured fetal cells to levels consistent with ADA-deficient SCID as determined by reference laboratory or confirmed ADA gene mutation(s) known to cause disease , AND
- Evidence of severe combined immunodeficiency based on either:
- Family history of first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency, OR
- Evidence of severe immunologic deficiency in subject prior to institution of immune restorative therapy, based on
Key exclusion criteria (40 listed)
- Age ≤ 1.0 months Appropriate organ function as outlined below must be observed within 60 days of entering this trial.
- Hematologic
- Infectious
- Pulmonary
- Cardiac
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 |
|---|---|---|
| Infusion of autologous EFS-ADA LV CD34+ (OTL-101)Also: OTL-101autologous EFS-ADA LV CD34+ cells (OTL-101) are infused intravenously | Genetic | Gene Therapy |
| busulfanBusulfan is used for non-myeloablative conditioning | Drug | Gene Therapy |
| PEG-ADA ERTPEG-ADA ERT is discontinued at Day +30 (-3/+15 days) after successful engraftment | Drug | Gene Therapy |
Primary outcome
Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Time frame: 12 months
Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101 or HSCT
Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Time frame: 12 months
Event-free survival is defined as the percentage of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death.
9 secondary outcomes
OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
Time frame: 24 months
EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
Time frame: 24 months
Vector Copy Number (VCN) in Peripheral Blood (PB) Granulocytes.
Time frame: 24 months
VCN in Peripheral Blood Mononuclear Cells (PBMCs)
Time frame: 24 months
ADA Activity in Erythrocytes
Time frame: 24 months
Reduction in Deoxyadenosine Nucleotide (dAXP) in Erythrocytes
Time frame: 24 months
Change From Baseline in CD3+ T Cell Counts (2 Years)
Time frame: 24 months
Number of Single Integration Sites Representing >30% of the Total Integration Sites (2 Years)
Time frame: 24 months
Severe Infection Rate Excluding the First Three Months After Treatment
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22968453Candotti F, Shaw KL, Muul L, Carbonaro D, Sokolic R, Choi C, Schurman SH, Garabedian E, Kesserwan C, Jagadeesh GJ, Fu PY, Gschweng E, Cooper A, Tisdale JF, Weinberg KI, Crooks GM, Kapoor N, Shah A, Abdel-Azim H, Yu XJ, Smogorzewska M, Wayne AS, Rosenblatt HM, Davis CM, Hanson C, Rishi RG, Wang X, Gjertson D, Yang OO, Balamurugan A, Bauer G, Ireland JA, Engel BC, Podsakoff GM, Hershfield MS, Blaese RM, Parkman R, Kohn DB. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Blood. 2012 Nov 1;120(18):3635-46. doi: 10.1182/blood-2012-02-400937. Epub 2012 Sep 11.
- Background: PubMed 24256635Carbonaro DA, Zhang L, Jin X, Montiel-Equihua C, Geiger S, Carmo M, Cooper A, Fairbanks L, Kaufman ML, Sebire NJ, Hollis RP, Blundell MP, Senadheera S, Fu PY, Sahaghian A, Chan RY, Wang X, Cornetta K, Thrasher AJ, Kohn DB, Gaspar HB. Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Mol Ther. 2014 Mar;22(3):607-622. doi: 10.1038/mt.2013.265. Epub 2013 Nov 20.
- Derived from this study: PubMed 33974366Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, Carbonaro-Sarracino DA, Soni K, Terrazas D, Snell K, Ikeda A, Leon-Rico D, Moore TB, Buckland KF, Shah AJ, Gilmour KC, De Oliveira S, Rivat C, Crooks GM, Izotova N, Tse J, Adams S, Shupien S, Ricketts H, Davila A, Uzowuru C, Icreverzi A, Barman P, Campo Fernandez B, Hollis RP, Coronel M, Yu A, Chun KM, Casas CE, Zhang R, Arduini S, Lynn F, Kudari M, Spezzi A, Zahn M, Heimke R, Labik I, Parrott R, Buckley RH, Reeves L, Cornetta K, Sokolic R, Hershfield M, Schmidt M, Candotti F, Malech HL, Thrasher AJ, Gaspar HB. Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency. N Engl J Med. 2021 May 27;384(21):2002-2013. doi: 10.1056/NEJMoa2027675. Epub 2021 May 11.
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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. This study is not recruiting at the moment.
Donald B Kohn, MD principal investigator
University of California, Los Angeles
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Infusion of autologous EFS-ADA LV CD34+ (OTL-101), busulfan and PEG-ADA ERT in people with ADA-SCID, run by University of California, Los Angeles at 2 sites in United States.
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 8 inclusion and 40 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: finished, as of the sponsor's last update on 3 Aug 2022. 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. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) (time frame: 12 months). The study lists 2 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 NCT01852071, which also lists 3 linked publications.
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 3 Aug 2022.