Gene-Editing breakthrough aims to fix immune cells in rare disease
NCT ID NCT06325709
First seen Jun 24, 2026 · Last updated Aug 14, 2026 · Updated 14 times
Summary
This early-stage trial tests a new gene-editing approach for X-linked chronic granulomatous disease (X-CGD), a rare immune disorder. Researchers will collect stem cells from 10 adult male participants, use base editing to correct the genetic mutation, and return the cells after mild chemotherapy. The goal is to restore white blood cell function and reduce life-threatening infections. Participants will be followed for 15 years to monitor safety and effectiveness.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- base-edited autologous hematopoietic stem and progenitor cells
- What this could lead to
- If successful, this could provide a one-time gene repair that restores white blood cell function, reducing severe infections and hospitalizations for people with X-linked CGD.
- What could go wrong
- This is an early-phase trial with only 10 participants, so results may not apply broadly. The chemotherapy conditioning and long-term immune suppression carry risks, and the gene correction may not be durable or effective enough.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1/2
Runs two stages together: safety and dose first, then whether the treatment works.
- Participants
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About 15 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Apr 2024
- Expected to finish
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Dec 2032
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 to 75 years
- Sex
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Male participants only
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
* INCLUSION CRITERIA: -\>= 18 years of age. * Confirmed CYBB c.676 C\>T mutation. * Male patients. * Clinically stable and eligible to undergo apheresis and conditioning chemotherapy. -\>=5 x 10\^6 cryopreserved cells/kg body weight available for study product manufacturing. * History of at least one prior serious infection or inflammatory complication requiring hospitalization despite conventional therapy. * In the experience of a qualified clinical investigator, the patient has a poor prognosis. * Able and willing to use a highly effective method of contraception, AND partner has communicated her willingness through subject to do same, if engaging in potentially reproductive sex from the signing of the informed consent and for 6 months after IMP infusion. Acceptable methods of contraception include the following: * Hormonal contraception in continuously effective use by female partner. * Male or female condom with spermicide as indicated. * Diaphragm or cervical cap in consistent and effective pattern of use with a spermicide by female partner. * Intrauterine device in-situ throughout above period by female partner. EXCLUSION CRITERIA: Individuals meeting any of the following criteria will be excluded from study participation: * Untreated, acute infection. * Elevated anti-gp91 specific autoantibodies \>2 x ULN * Elevated anti-gp91 specific T cells (\>10 fold) * Anti-platelet antibody screening with \>1 anti-platelet antibody positive in the presence of an ongoing brain infection; OR \>1 anti-platelet antibody positive and considered unsafe for study participation after consultation with hematology specialist. * Known hypersensitivity to busulfan or any component of the product. * Contraindications for administration of busulfan. * Any current or pre-existing hematologic malignancy. * Chronic infections that are considered unsafe for participation in the study by Infectious Disease Consultant. * Cardiac abnormalities and neurological abnormalities that are deemed unsafe to participate in the study. * Childhood malignancy (occurring before 18 years of age) in the patient or a first degree relative, or previously diagnosed known genotype of the participant conferring a predisposition to cancer (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol). * Hematological parameters unsafe for apheresis or above Grade 2 Common Terminology Criteria for Adverse Events (CTCAE) criteria until improved. * Hepatic dysfunction- alanine aminotransferase (ALT \>3.0 - 5.0 x upper limit of normal \[ULN\]), aspartate aminotransferase (AST \>3.0 - 5.0 x ULN), bilirubin (\>1.5 - 3.0 x ULN). * Renal dysfunction-serum creatinine \>1.5 - 3.0 x ULN or creatinine clearance 59-30 mL/min/1.73 m\^2. * Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time \>2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels). * Uncontrolled hypertension- Systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg. * Abnormal blood chemistries- Hyperkalemia (K \>5.5 - 6.0 mmol/L), Hypokalemia (\<LLN - 3.0 mmol/L and requiring intervention); OR Hypercalcemia (corrected serum calcium \>11.5 - 12.5 mg/dL), Hypocalcemia (corrected serum calcium \<8.0 -7.0 mg/dL) These values exclude false abnormalities secondary to hemolysis. * Cytogenetic abnormalities evidenced on bone marrow aspirate. * Pulmonary dysfunction FEV1\<25% predicted. * Previous treatment with gene therapy or gene editing products. * Previous receipt of non-HLA matched donor granulocyte transfusions. * Any other condition that, in the opinion of the investigator, may unduly compromise the safety or compliance of the patient, or would make successful study completion highly unlikely. * Unwilling to submit their information as part of the alemtuzumab (Campath(R)) Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab. NOTE: Alemtuzumab (campath) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore, no gene therapy will occur on this protocol.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
1 site. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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National Institutes of Health Clinical Center
RECRUITINGBethesda, Maryland, 20892, United States
More trials for these conditions
Other studies related to the condition(s) this trial covers.
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