Severe Combined Immunodeficiency Due to ADA DeficiencyPhase 1/2NCT02999984
Efficacy and Safety of the Cryopreserved Formulation of OTL-101 in Subjects With ADA-SCID
A Phase 1/2 study testing Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101), busulfan and PEG-ADA ERT in people with Severe Combined Immunodeficiency Due to ADA Deficiency, run by University of California, Los Angeles at 1 site in United States.
Trial summary
This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101 (autologous CD34+ hematopoietic stem/progenitor cells transduced ex vivo with EFS (Elongation Factor 1α Short form) Lentiviral Vector… Read more about this study
- Who is it for?
- Ages 30 days to 17 years
- Conditions the study is for
- Severe Combined Immunodeficiency Due to ADA Deficiency
- What is being tested?
- Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (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
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2016to 26 Sep 2019
- 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 30 days to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Provision of written informed consent prior to any study related procedures. In this study consent must be provided by the parents/legal guardians and, where applicable according to local laws, a signed assent from the child,
- Subjects ≥30 days and <18 years of age,
- With a diagnosis of ADA-SCID based on:
- Evidence of ADA deficiency, defined as:
- Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured fetal cells to levels consistent with ADA-SCID as determined by the reference laboratory, or ii. Identified mutations in ADA alleles consistent with a severe reduction in ADA activity,
- Evidence of ADA-SCID based on either:
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- Family history of a first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency, or ii. Evidence of severe immunologic deficiency in subjects prior to the institution of immune restorative therapy, based on
- Lymphopenia (absolute lymphocyte count (ALC) <400 cells/µL) OR absence or low number of T cells (absolute CD3+ count < 300 cells/µL), or
- Severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (either <10% of lower limit of normal controls for the diagnostic laboratory, or <10% of the response of the normal control of the day, or stimulation index <10), or
- Identification of SCID by neonatal screening revealing low T cell Receptor Excision Circle (TREC) levels.
- Ineligible for matched family allogeneic Bone Marrow (BM) transplantation, defined as the absence of a medically eligible HLA-identical sibling or family donor, with normal immune function, who could serve as an allogeneic bone marrow donor.
- Females of child-bearing age will be required to provide a negative pregnancy test 30 days prior to Visit 2.
- Subjects and their parents/legal guardians must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow up evaluation as specified in the protocol.
Who cannot join
- Ineligible for autologous Hematopoietic Stem Cell Transplantation (HSCT) as per clinical site criteria.
- Other conditions which in the opinion of the Principal Investigator and/or Co Investigators, contraindicate the harvest of bone marrow, the administration of Busulfan and the infusion of transduced cells, or which indicate an inability of the subject or subject's parent/legal guardian to comply with the protocol.
- Hematologic abnormality, defined as:
- Anemia (Hb <8.0 g/dl).
- Neutropenia (ANC <500/mm3). Note: ANC <500 with absence of myelodysplastic syndrome on bone marrow aspirate and biopsy and normal marrow cytogenetics are acceptable for eligibility.
- Thrombocytopenia (platelet count <50,000/mm3, at any age).
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- Prothrombin time or international normalized ratio (INR) and partial thromboplastin time (PTT) >2 x upper limit of normal (ULN) (subjects with a correctable deficiency controlled on medication will not be excluded).
- Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid (if available).
- Prior allogeneic HSCT with cytoreductive conditioning.
- Pulmonary abnormality, defined as:
- Resting O2 saturation by pulse oximetry <90% on room air.
- Chest X-ray indicating active or progressive pulmonary disease. Note: Chest X ray indicating residual signs of treated pneumonitis is acceptable for eligibility.
- Cardiac abnormality, defined as:
- Abnormal ECG indicating cardiac pathology.
- Uncorrected congenital cardiac malformation with clinical symptoms.
- Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension.
- Poor cardiac function as evidenced by left ventricular ejection fraction <40% on echocardiogram.
- Neurologic abnormality, defined as:
- Significant neurologic abnormality revealed by examination.
- Uncontrolled seizure disorder.
- Renal abnormality, defined as:
- Renal insufficiency: serum creatinine ≥1.2 mg/dl (106 µmol/L), or ≥3+ proteinuria.
- Abnormal serum sodium, potassium, calcium, magnesium or phosphate levels at >2 x ULN.
- Hepatic/gastrointestinal abnormality, defined as:
- Serum transaminases >5 x ULN.
- Serum bilirubin >2 x ULN.
- Serum glucose >1.5 x ULN.
- Oncologic disease, defined as:
- 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 (if anti-neoplastic therapy has been completed, a subject with a history of DFSP can be included).
- Evidence of DFSP expected to be life limiting within the 5 years following the infusion of genetically corrected cells.
- Known sensitivity to Busulfan.
- Confirmation of an infectious disease by deoxyribonucleic acid (DNA) Polymerase chain reaction (PCR) positive at time of screening assessment for the following:
- HIV-1,
- Hepatitis B,
- Parvovirus B19.
- The subject is pregnant or has a major congenital anomaly.
- Is likely to require treatment during the study with drugs that are not permitted by the study protocol.
- The subject has previously received another form of gene therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles
Los Angeles, California, 90095
About this study
Official title: Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency
This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101 (autologous CD34+ hematopoietic stem/progenitor cells transduced ex vivo with EFS (Elongation Factor 1α Short form) Lentiviral Vector (LV) encoding for the human ADA gene) administered to ADA-SCID subjects between the ages of 30 days and 17 years of age, who are not eligible for an Human Leukocyte Antigen (HLA) matched sibling/family donor and meeting the inclusion/exclusion criteria. The OTL-101 product is infused after a minimal interval of at least 24 hours following the completion of reduced intensity conditioning. For subjects who successfully receive the OTL-101 product, pegademase bovine (PEG-ADA) Enzyme Replacement Therapy (ERT) is discontinued at Day+30 (-3/+15) after the transplant. After their discharge from hospital, the subjects will be seen at regular intervals to review their history, perform examinations and draw blood samples to assess immunity and safety.
- Being tested
- Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101), busulfan, PEG-ADA ERT
- Keywords
- gene therapy, hematopoietic and progenitor cells, lentiviral vector, ADA-SCID
- Medical subject headings
- Severe combined immunodeficiency due to adenosine deaminase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101)Genetic
Also called OTL-101
autologous cryopreserved 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 cryopreserved EFS-ADA LV CD34+ cells Receives: Genetic: Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (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.
Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months)
Efficacy of OTL-101 treatment at 6 months post OTL-101 infusion based on the following parameters and thresholds:
- ADA enzyme activity in erythrocytes above baseline/pretreatment level (i.e., >0 units). ADA enzyme activity is measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV.
- Absolute CD3+ T cell counts ≥200 cells/μL. Increase in CD3+ T cell counts is a marker of immune reconstitution.
- Granulocyte samples positive for vector sequences by quantitative Polymerase Chain Reaction (PCR) (≥1/10,000 cells). Vector copy number (VCN) in the Peripheral Blood (PB) Granulocytes 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.
Measured: 6 months
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 cryopreserved OTL-101.
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 (7)
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 cryopreserved OTL-101.
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
Change From Baseline in CD3+ T Cell Counts (2 Years)
Immune reconstitution was assessed by change in CD3+ T Cell counts over time.
Measured: 24 months
Severe Infections Excluding First 3 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
Change From Baseline in Quality of Life Measures (2 Years)
Assessment of quality of life was measured by the Lansky Performance Status Scale. The maximum score on the Lansky Performance Scale is 100 - the child is fully active and able to carry on normal activity with no special care needed. The minimum score is 10 - the child is completely disabled, not even passive play. The scores at baseline (pre-treatment with OTL-101) and scores at Month 24 post-treatment with OTL-101 were compared to establish if there were any changes in the child's score in this timeframe.
Measured: 24 months
Percentage of Patients Who Stopped Immunoglobulin Replacement Therapy (IgRT) (2 Years)
Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. Indications for considering the discontinuation of immunoglobulin replacement therapy included: absolute CD4+ >200, absolute B cell >100/μl, IgA or IgM > lower limit of normal for age or gene marking >1% detectable in B cells.
Measured: 24 months
Time to Cessation of IgRT for Those Who Stopped (2 Years)
Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. For subjects who stopped IgRT during the study, the time of cessation was recorded.
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 posted21 Dec 2016 (estimated)
- Study start16 Dec 2016
- Primary completion11 Oct 2018
- Study completion26 Sep 2019
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 (2)Papers the sponsor has linked to this study.
- Other trials for Severe Combined Immunodeficiency Due to ADA 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM), Orchard Therapeutics
- Responsible party
- Principal investigator, Donald B. Kohn, M.D., University of California, Los Angeles
- Investigators
- Donald B. Kohn, MD, Study director, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02999984
- Sponsor's protocol ID
- OTL-101-4
- Status last verified
- Aug 2022
- First submitted
- 19 Dec 2016
- Last updated
- 3 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Publications
Carbonaro 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
- Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency
- ClinicalTrials.gov ID
- NCT02999984
- Acronym / sponsor ID
- OTL-101-4
- Keywords
- gene therapy, hematopoietic and progenitor cells, lentiviral vector, ADA-SCID
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM), Orchard Therapeutics
- Study start
- 16 Dec 2016 (actual)
- Primary completion
- 11 Oct 2018 (actual)
- Study completion
- 26 Sep 2019 (actual)
- First posted
- 21 Dec 2016 (estimated)
- Results
- Posted 22 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101 (autologous CD34+ hematopoietic stem/progenitor cells transduced ex vivo with EFS (Elongation Factor 1α Short form) Lentiviral Vector (LV) encoding for the human ADA gene) administered to ADA-SCID subjects between the ages of 30 days and 17 years of age, who are not eligible for an Human Leukocyte Antigen (HLA) matched sibling/family donor and meeting the inclusion/exclusion criteria. The OTL-101 product is infused after a minimal interval of at least 24 hours following the completion of reduced intensity conditioning. For subjects who successfully receive the OTL-101 product, pegademase bovine (PEG-ADA) Enzyme Replacement Therapy (ERT) is discontinued at Day+30 (-3/+15) after the transplant. After their discharge from hospital, the subjects will be seen at regular intervals to review their history, perform examinations and draw blood samples to assess immunity and safety.
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 cryopreserved EFS-ADA LV CD34+ cells (OTL-101), Drug: busulfan, Drug: PEG-ADA ERTInfusion of autologous cryopreserved EFS-ADA LV CD34+ cells |
Who may qualify
- Ages
- 30 days to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- Provision of written informed consent prior to any study related procedures. In this study consent must be provided by the parents/legal guardians and, where applicable according to local laws, a signed assent from the child,
- Subjects ≥30 days and <18 years of age,
- With a diagnosis of ADA-SCID based on:
- Ineligible for matched family allogeneic Bone Marrow (BM) transplantation, defined as the absence of a medically eligible HLA-identical sibling or family donor, with normal immune function, who could serve as an allogeneic bone marrow donor.
- Females of child-bearing age will be required to provide a negative pregnancy test 30 days prior to Visit 2.
Key exclusion criteria (39 listed)
- Ineligible for autologous Hematopoietic Stem Cell Transplantation (HSCT) as per clinical site criteria.
- Other conditions which in the opinion of the Principal Investigator and/or Co Investigators, contraindicate the harvest of bone marrow, the administration of Busulfan and the infusion of transduced cells, or which indicate an inability of the subject or subject's parent/legal guardian to comply with the protocol.
- Hematologic abnormality, defined as:
- Pulmonary abnormality, defined as:
- Cardiac abnormality, defined as:
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 cryopreserved EFS-ADA LV CD34+ cells (OTL-101)Also: OTL-101autologous cryopreserved 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
Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months)
Time frame: 6 months
Efficacy of OTL-101 treatment at 6 months post OTL-101 infusion based on the following parameters and thresholds: 1. ADA enzyme activity in erythrocytes above baseline/pretreatment level (i.e., >0 units). ADA enzyme activity is measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV. 2. Absolute CD3+ T cell counts ≥200 cells/μL. Increase in CD3+ T cell counts is a marker of immune reconstitution. 3. Granulocyte samples positive for vector sequences by quantitative Polymerase Chain Reaction (PCR) (≥1/10,000 cells). Vector copy number (VCN) in the Peripheral Blood (PB) Granulocytes 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.
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 cryopreserved OTL-101.
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.
7 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
Change From Baseline in CD3+ T Cell Counts (2 Years)
Time frame: 24 months
Severe Infections Excluding First 3 Months After Treatment
Time frame: 24 months
Change From Baseline in Quality of Life Measures (2 Years)
Time frame: 24 months
Percentage of Patients Who Stopped Immunoglobulin Replacement Therapy (IgRT) (2 Years)
Time frame: 24 months
Time to Cessation of IgRT for Those Who Stopped (2 Years)
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 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.
- Background: 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.
- Pre-clinical activity and safety dataLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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 study director
University of California, Los Angeles
1 site 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 cryopreserved EFS-ADA LV CD34+ cells (OTL-101), busulfan and PEG-ADA ERT in people with Severe Combined Immunodeficiency Due to ADA Deficiency, run by University of California, Los Angeles at 1 site 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 13 inclusion and 39 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 1 site 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 22 Jul 2022). 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?
Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months) (time frame: 6 months). 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 NCT02999984, which also lists 2 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.