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Severe Combined Immunodeficiency Due to ADA DeficiencyPhase 2/3NCT04140539

A Clinical Study to Enable Process Validation of Commercial Grade OTL-101

A Phase 2/3 study testing OTL-101 in people with Severe Combined Immunodeficiency Due to ADA Deficiency, run by University of California, Los Angeles at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of the current study is to treat at least 3 ADA-SCID patients with OTL-101 prepared by the commercial manufacturing process. Read more about this study

Who is it for?
Ages 30 days to 17 years
What is being tested?
OTL-101
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
15 Oct 2019to 30 Aug 2021
Phase
Phase 2/3
Are there results?
None posted in the registry

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 by the subject or parent(s)/legal guardian(s), prior to any study related procedures taking place. Where consent is provided by the parent(s)/legal guardian(s), assent by the subject should also be sought, if appropriate
  • Age ≥30 days and <18 years
  • Diagnosis of ADA-SCID based on either:
  • 1) 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 Identified mutations in ADA alleles consistent with a severe reduction in ADA activity
  • 2) Evidence of ADA-SCID, defined as Family history of a first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency OR Evidence of severe immunologic deficiency in subjects prior to the institution of immune restorative therapy, based on at least one of the following:
  • Lymphopenia (absolute lymphocyte count <400 cells/μL) OR absence or low number of T cells (absolute CD3+ count < 300 cells/μL)
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  • 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)
  • Identification of SCID by neonatal screening revealing low T cell receptor excision circles (TREC) levels
  • Ineligible for allogeneic bone marrow transplantation from an Human leukocyte antigen (HLA)-identical sibling donor, with normal immune function
  • For females of child-bearing potential, negative pregnancy test up to 30 days prior to the Screening visit. For all subjects in the reproductive age range, agreement to use highly effective and adequate method of contraception while receiving treatment and for at least 12 months following drug administration
  • Willingness and ability of the subjects and parent(s)/legal guardian(s) to comply with study procedures and requirements, including remaining at the clinic for the required duration of conditioning and treatment and compliance with follow-up evaluations

Who cannot join

  • Ineligible for autologous HSCT as per clinical site criteria.
  • Hematologic abnormality, defined as:
  • Anemia (Hb <8.0 g/dL)
  • Neutropenia (absolute neutrophil count (ANC) <500 cells/mm3). Note: ANC <500 cells/mm3 with absence of myelodysplastic syndrome on bone marrow aspirate and biopsy and normal marrow cytogenetics are acceptable for eligibility
  • Thrombocytopenia (platelet count <50,000 platelets/mm3)
  • Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial thromboplastin time (PTT) >2 times the upper limit of normal (ULN) (subjects with a correctable deficiency controlled on medication will not be excluded)
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  • Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid (if available)
  • Prior allogeneic HSCT with cytoreductive conditioning
  • Pulmonary abnormality, defined as:
  • Resting oxygen (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 electrocardiogram 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 times the ULN
  • Hepatic/gastrointestinal abnormality, defined as:
  • Serum transaminases >5 times the ULN
  • Serum bilirubin >2 times the ULN
  • Serum glucose >1.5 times the 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 infectious disease at time of Screening assessment for:
  • Human Immunodeficiency Virus (HIV)-1 and HIV-2
  • Hepatitis B and Hepatitis C
  • Parvovirus B19
  • Human T-cell lymphotropic virus (HTLV)-1 and HTLV-2
  • Pregnant at the time of Screening
  • Affected by a major congenital anomaly
  • Likely to require treatment during the study with drugs that are not permitted by the study protocol
  • Previously treated with another form of gene therapy
  • Affected by any other condition(s) which, in the opinion of the Principal Investigator, contraindicate bone marrow harvest, the administration of busulfan and the infusion of OTL-101, or which indicate an inability of the subject or subject's parent(s)/legal guardian(s) to comply with the protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, Los Angeles

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: A Single Arm, Open Label Clinical Study to Enable Process Validation of Commercial Grade Ex Vivo Hematopoietic Stem Cell Gene Therapy (OTL-101) in Subjects With Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)

The purpose of the current study is to treat at least 3 ADA-SCID patients with OTL-101 prepared by the commercial manufacturing process.

Read the detailed description

The safety and efficacy of OTL-101 for the treatment of patients with ADA- SCID have been established in previous clinical trials. The purpose of the current study is to treat at least 3 ADA-SCID patients with OTL-101 prepared by the commercial manufacturing process in order to facilitate collection of data necessary for final manufacturing.

Assessments will focus on monitoring safety and engraftment, through the evaluation of parameters describing immunological recovery, ADA enzyme activity and persistence of gene marking (VCN) at 6 months and 12 months. After completion of 12 months of follow-up on the current study protocol, subjects will be enrolled in an observational long-term follow-up study, in order to monitor the long-term safety of treatment with OTL-101.

Being tested
OTL-101
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.

  • OTL-101Biological

    Autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo using a lentiviral vector (LV) encoding the human adenosine deaminase (ADA) gene.

Study groups in NCT04140539
Study groupRoleWhat they receive
Gene TherapyExperimentalInfusion OTL-101
Receives: Biological: OTL-101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adenosine Deaminase (ADA) enzyme activity

    ADA enzyme activity in red blood cells

    Measured: 6 months post treatment

  2. T cell (CD3+) count

    Absolute count of CD3+ cells

    Measured: 6 months post treatment

  3. Vector Copy Number (VCN)

    VCN in granulocytes

    Measured: 6 months post treatment

Secondary outcomes (2)

  1. Overall Survival (OS)

    OS will be defined as the proportion of subjects alive at 12 months post-treatment with OTL-101

    Measured: 12 months post treatment

  2. Event-free Survival (EvFS)

    EvFS will be defined as the proportion of subjects alive with no "event", an event being the resumption of Pegylated adenosine deaminase (PEG-ADA) Enzyme Replacement Therapy (ERT) or the need for a rescue allogeneic hematopoietic stem cell transplant (HSCT) at 12 months post-treatment with OTL-101

    Measured: 12 months post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2019
  2. Study start15 Oct 2019
  3. Primary completion30 Aug 2021
  4. Study completion30 Aug 2021

Why it stopped: Recruitment on hold for business reasons. Study will not be performed.

Resources

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 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04140539
Sponsor's protocol ID
OTL-101-7
Status last verified
Aug 2022
First submitted
24 Oct 2019
Last updated
3 Aug 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing OTL-101 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 11 inclusion and 41 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: withdrawn, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Adenosine Deaminase (ADA) enzyme activity (time frame: 6 months 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 NCT04140539.

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.

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