Clinical Trial

Disease: X-Linked Severe Combined Immunodeficiency, (NCT06851767)

Disease info:

X-linked severe combined immunodeficiency is an inherited disorder of the immune system that occurs almost exclusively in males. Children with this condition are prone to recurrent and persistent infections because they lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. The condition is caused by variants in the IL2RG gene, which provides instructions for making a protein critical for normal immune system function and the growth and maturation of lymphocytes.

If untreated, infants with X-linked severe combined immunodeficiency can develop poor growth, chronic diarrhoea, a fungal infection called thrush, skin rashes, and life-threatening infections. The condition can be detected shortly after birth by newborn screening, which allows for prompt treatment.

X-linked severe combined immunodeficiency is the most common form of severe combined immunodeficiency disorders. The incidence of all severe combined immunodeficiency disorders is 1 in 60,000 newborns, and it is estimated that one-quarter to one-third of these cases are X-linked. The condition is inherited in an X-linked recessive pattern, with males being affected much more frequently than females as they have only one X chromosome.

Source: Medline Plus

Frequency:
The incidence of all severe combined immunodeficiency disorders is 1 in 60,000 newborns, and it is estimated that one-quarter to one-third of these cases are X-linked.
Official title:
Phase 1/2 Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy
Who:

Principal Investigator: Suk S De Ravin, M.D.,National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Partners:
Locations:

 

United States, Maryland Bethesda, Maryland, United States, 20892 Recruiting National Institutes of Health Clinical Center

Study start:
May. 9, 2025
Enrollment:
18
Gene editing method:
Base editing
Type of edit:
Gene correction
Gene:
IL2RG
Delivery method:
- Ex-vivo
Trial link:
https://clinicaltrials.gov/study/NCT06851767?term=nct06851767&rank=1
IndicatorIndicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Enrolling by invitation

Description

Study Description:

This is a phase 1/2, non-randomized study of a single infusion of autologous hematopoietic stem/progenitor cells base-edited to repair interleukin 2 receptor gamma (IL2RG) mutations (BE-HSPC IL2RG) in 18 participants with X-linked severe combined immunodeficiency (X-SCID).

Primary Objective:

Evaluate the safety of treatment with BE-HSPC IL2RG in participants with X-SCID.

Secondary Objectives:

Evaluate efficacy of treatment with BE-HSPC IL2RG in participants with X-SCID.

Exploratory Objectives:

  1. Evaluate off-target (OT) editing activity.
  2. Compare outcomes of immune reconstitution with lentivector (LV) gene therapy.

Primary Endpoint:

Safety of treatment with BE-HSPC IL2RG, by quantifying frequency and severity of adverse events (AEs) related to study agent from infusion to 12 months after infusion.

Secondary Endpoints (24 months post-study agent infusion):

  1. Percentage of participants with >=5% mutation-repaired myeloid cells.
  2. Editing efficiency in peripheral blood cells (such as T, B, and natural killer [NK] cells).

  3. Immune reconstitution:

    1. T, B, and NK cell number improvement from baseline.
    2. Emergence of naive T cells and CD31+ recent thymic emigrants.
    3. B-cell function: immunoglobulin (Ig) production.
    4. Specific responses to vaccines.
  4. Clinical efficacy: improvement from baseline problems such as recurrent infection, chronic norovirus, protein-losing enteropathy, gastrointestinal complaints, growth failure, malnutrition, or immune dysregulation.
  5. Frequency and severity of all study agent-related AEs and serious adverse events (SAEs) from time of study product infusion.

Exploratory Endpoints:

  1. Evaluate for frequency of off-targets (OTs) by high-throughput sequencing (HTS) of the target mutation at 2 years post-infusion.
  2. Compare rates of immune reconstitution with LV-X-SCID gene therapy.
Last updated: Jun. 23, 2025
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