AzTrials
AzTrials

Severe Combined Immunodeficiency Due to ADA DeficiencyPhase 1/2NCT03765632

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 in people with Severe Combined Immunodeficiency Due to ADA Deficiency, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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
What is being tested?
Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101), Busulfan and Peg-Ada
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited Kingdom
Study dates
3 Jan 2018to 28 Sep 2022
Phase
Phase 1/2
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 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: i. Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured foetal 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: i. 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 <400 cells/mL) OR absence or low number of T-cells (absolute CD3+ count < 300 cells/mL), or
Show all 11Show fewer
  • 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 or with no available matched family donor for 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 (HSC) procedure.
  • 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.
  • Haematologic abnormality, defined as:
  • Anaemia (Hb <8.0 g/dl). Evidence of bi/trilineage cytopaenia (haemoglobin <8 g/dl, neutrophils <0.5 x 109/L, platelets 50 x 109/L). Thrombocytopaenia (platelet count <50,000/mm3). Prothrombin time or 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 of Peripheral Blood (PB), BM or amniotic fluid (if available). If cytogenetic testing has not been performed on cells from amniocentesis, assessment should be by karyotype, Comparative genomic hybridization (CGH), and or whole exome sequencing (WES).
  • Prior allogeneic HSC transplant (HSCT) with cytoreductive conditioning.
Show all 28Show fewer
  • 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.
  • Known history of significant renal abnormality.
  • Known history of significant hepatic or gastrointestinal abnormality.
  • Oncologic disease, defined as:
  • Evidence of active malignant disease other than Dermatofibrosarcoma Protuberans( DFSP) 2.
  • 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 reactions (PCR) positive at time of screening assessment according to local protocols/procedures (including HIV-1 and hepatitis B).
  • 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 Kingdom1 site

  • Great Ormond Street Hospital for Children NHS Foundation Trust

    London, WC1N 3JH

Other trials in United Kingdom

About this study

Official title: Efficacy and Safety of a Cryopreserved Formulation of Autologous CD34+ Haematopoietic Stem Cells Transduced ex Vivo With Elongation Factor 1α Short Form (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency (SCID) Due to Adenosine Deaminase 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 <18 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
Keywords
Gene therapy, Hematopoietic stem 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-AdaDrug

    Peg-Ada Enzyme Replacement Therapy (ERT) is discontinued at Day +30 (-3/+15 days) after successful engraftment

Study groups in NCT03765632
Study groupRoleWhat they receive
Gene TherapyExperimentalInfusion 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

What is being measured

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

  1. Overall survival at 12 months post OTL-101 infusion

    Overall survival is defined as the proportion of subjects alive

    Measured: 12 Months

  2. Event free survival at 12 months post OTL-101 infusion

    Event-free survival is defined as the proportion of subjects alive with no "event", an "event" being the resumption of Peg-Ada ERT or the need for a rescue stem cell transplant (SCT), or death

    Measured: 12 Months

Secondary outcomes (5)

  1. Overall survival at 24 months post OTL-101 infusion

    Overall survival is defined as the proportion of subjects alive

    Measured: 24 months

  2. Event free survival at 24 months post OTL-101 infusion

    Event-free survival is defined as the proportion of subjects alive with no "event", an "event" being the resumption of Peg-Ada ERT or the need for a rescue stem cell transplant (SCT), or death

    Measured: 24 Months

  3. Safety evaluation including infection rates

    Measured: 12 and 24 months

  4. Safety evaluation including performance outcomes

    Measured: 12 and 24 months

  5. Safety evaluation including immune reconstitution

    Measured: 12 and 24 months

Timeline

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

  1. First posted5 Dec 2018
  2. Study start3 Jan 2018
  3. Primary completion13 Sep 2021
  4. Study completion28 Sep 2022

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03765632
Sponsor's protocol ID
OTL-101-5
Other IDs
17IC04
Status last verified
Jan 2023
First submitted
8 Aug 2018
Last updated
1 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

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 in people with Severe Combined Immunodeficiency Due to ADA Deficiency, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.

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 28 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 1 Feb 2023. 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 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.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 at 12 months post OTL-101 infusion (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 NCT03765632.

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 1 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in