Phase 2
N=10
Efficacy and Safety of the Cryopreserved Formulation of OTL-101 in Subjects With ADA-SCID
Severe Combined Immunodeficiency Due to ADA Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT02999984 ↗Enrolled (actual)
10
Serious AEs
30.0%
Results posted
Jul 2022
Primary outcome: Primary: Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months) — 100; 100; 90 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101) (Genetic); busulfan (Drug); PEG-ADA ERT (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- University of California, Los Angeles
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months) |
100; 100; 90 | — |
| PRIMARY Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) |
100 | — |
| PRIMARY Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) |
90.00; 90.00; 100 | — |
| SECONDARY OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) |
100 | — |
| SECONDARY EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) |
90.00; 90.00; 100 | — |
| SECONDARY Change From Baseline in CD3+ T Cell Counts (2 Years) |
418.5 | — |
| SECONDARY Severe Infections Excluding First 3 Months After Treatment |
0.12 | — |
| SECONDARY Change From Baseline in Quality of Life Measures (2 Years) |
— | — |
| SECONDARY Percentage of Patients Who Stopped Immunoglobulin Replacement Therapy (IgRT) (2 Years) |
78 | — |
| SECONDARY Time to Cessation of IgRT for Those Who Stopped (2 Years) |
11.6 | — |
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 (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.
Eligibility Criteria
Inclusion Criteria
- 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 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 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.
Data sourced from ClinicalTrials.gov (NCT02999984). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.