20 Participants Needed

Gene Therapy for Severe Combined Immunodeficiency (SCID)

SD
AF
SD
Overseen BySatiro De Oliveira, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: University of California, Los Angeles
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from mobilized peripheral blood (mPB) of ADA-deficient SCID infants and children following human ADA gene transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants likely to require treatment with drugs not permitted by the study protocol are excluded, suggesting some medications might not be allowed.

What data supports the effectiveness of the treatment EFS-ADA Lentiviral Vector, OTL-101 for Severe Combined Immunodeficiency (SCID)?

Gene therapy has shown to be effective in treating severe combined immunodeficiencies, including those caused by adenosine deaminase deficiency, by providing sustained correction of T-cell deficiencies. Improved safety and effectiveness have been achieved with newer lentiviral vectors, which are more potent and safer than earlier versions.12345

Is gene therapy for SCID generally safe in humans?

Gene therapy for SCID has shown a good safety profile in humans, with most adverse events being mild to moderate and not related to the therapy itself. However, there have been rare cases of severe complications, such as leukemia-like conditions, in some patients with X-linked SCID, which have been addressed by improving the therapy's design.26789

How is the treatment EFS-ADA Lentiviral Vector (OTL-101) unique for SCID?

The EFS-ADA Lentiviral Vector (OTL-101) is unique because it uses a self-inactivating lentiviral vector to deliver a corrected gene into the patient's own stem cells, which reduces the risk of causing cancer compared to older methods. This approach aims to provide a safer and more effective long-term correction of the immune deficiency in SCID patients.125910

Research Team

SD

Satiro De Oliveira, MD

Principal Investigator

Assistant Professor

Eligibility Criteria

This trial is for infants and children with ADA-SCID, a genetic disorder that affects the immune system. Participants must be at least 30 days old, unable to undergo bone marrow transplant from a family donor, and able to follow study procedures. Pregnant individuals or those with certain organ dysfunctions or previous gene therapy are excluded.

Inclusion Criteria

I am older than 30 days.
I am a woman of child-bearing age and can provide a negative pregnancy test.
I don't have a family member who can donate bone marrow to me.
See 4 more

Exclusion Criteria

The subject is pregnant or has a major congenital anomaly
You have a positive test for HIV-1, Hepatitis B, or Parvovirus B19.
My kidney function is not normal, or I have very high levels of sodium, potassium, calcium, magnesium, or phosphate.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive pharmacokinetically-adjusted busulfan reduced intensity conditioning prior to re-infusion of their gene-modified cells

1-2 weeks

Treatment

Autologous CD34+ cells transduced with EFS-ADA lentiviral vector are infused into participants

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, including immune reconstitution and cessation of PEG-ADA ERT

24 months

Long-term follow-up

Participants may enroll in a long-term follow-up study to reach a total of 15 years post-gene therapy

Treatment Details

Interventions

  • EFS-ADA Lentiviral Vector
Trial OverviewThe trial tests a treatment where patients' own blood stem cells are modified outside the body using a special virus that carries a correct copy of the ADA gene. These modified cells are then returned to the patient's body to help restore their immune function.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Autologous mobilized peripheral blood (mPB) transduced with EFS ADA lentiviral vectorExperimental Treatment1 Intervention
Evaluate safety and efficacy of this autologous gene therapy

EFS-ADA Lentiviral Vector is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as OTL-101 for:
  • Adenosine Deaminase Severe Combined Immunodeficiency (ADA SCID)
🇪🇺
Approved in European Union as OTL-101 for:
  • Adenosine Deaminase Severe Combined Immunodeficiency (ADA SCID)

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials
1,594
Recruited
10,430,000+

Findings from Research

Gene therapy has shown promising results in treating severe combined immunodeficiency (SCID) by correcting T-cell immunodeficiency, with sustained effects observed in clinical trials over the past decade.
Advancements in vector technology, such as the use of lentiviral vectors and the removal of oncogenic elements from retroviral vectors, aim to enhance the safety and efficacy of gene therapy, reducing the risk of leukemia associated with earlier treatments.
Gene therapy for primary adaptive immune deficiencies.Fischer, A., Hacein-Bey-Abina, S., Cavazzana-Calvo, M.[2013]
Gene therapy has been shown to effectively correct T cell immunodeficiencies in severe combined immunodeficiencies (SCID), specifically for SCID-X1 and adenosine deaminase deficiency.
The shift from first-generation retroviral vectors to self-inactivated (SIN) retroviral or lentiviral vectors aims to maintain efficacy while improving safety, reducing the risk of gene toxicity observed in earlier trials.
Gene therapy of primary T cell immunodeficiencies.Fischer, A., Hacein-Bey-Abina, S., Cavazzana-Calvo, M.[2013]
A clinical trial initiated in 1990 demonstrated that retroviral-mediated gene therapy using the ADA gene in T cells of two children with severe combined immunodeficiency (ADA-SCID) resulted in normalized T cell counts and improved immune responses.
The effects of the gene therapy persisted for two years after treatment, indicating that gene therapy can be a safe and effective long-term option for managing this severe immunodeficiency.
T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.Blaese, RM., Culver, KW., Miller, AD., et al.[2022]

References

Gene therapy for primary adaptive immune deficiencies. [2013]
Gene therapy of primary T cell immunodeficiencies. [2013]
T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years. [2022]
Gene therapy of X-linked severe combined immunodeficiency. [2019]
Gene therapy for severe combined immunodeficiency caused by adenosine deaminase deficiency: improved retroviral vectors for clinical trials. [2017]
[Gene therapy of severe combined immunodeficiency disease: proof of principle of efficiency and safety issues. Gene therapy, primary immunodeficiencies, retrovirus, lentivirus, genome]. [2012]
Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety. [2021]
In Vivo Gene Therapy for Canine SCID-X1 Using Cocal-Pseudotyped Lentiviral Vector. [2022]
[Gene therapy for adenosine deaminase deficiency]. [2012]
10.United Statespubmed.ncbi.nlm.nih.gov
Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. [2023]