X-Linked Chronic Granulomatous DiseasePhase 1/2NCT06876363
Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease
A Phase 1/2 study testing EN-374 in people with X-Linked Chronic Granulomatous Disease, run by Ensoma at 9 sites in 2 countries.
Trial summary
The goal of this clinical trial is to evaluate the safety and potential efficacy of the EN-374 treatment regimen and identify a dose level for further evaluation in participants with x-linked chronic granulomatous disease. Read more about this study
- Who is it for?
- Ages 3 months and older, men only
- Conditions the study is for
- X-Linked Chronic Granulomatous Disease
- What is being tested?
- EN-374
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 5 Aug 2025to Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 3 months and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male
- ≥ 18 years of age during dose escalation, then ≥ 3 months of age during dose expansion
- Diagnosis of X-CGD with a pathogenic mutation in the CYBB gene
- History of at least 1 severe infection requiring medical intervention or chronic inflammatory disorder
- Does not have a suitable, available, and willing human leukocyte antigens (HLA)-matched (10/10) related donor
- Non-sterile male participants who are or may become sexually active with female partners of childbearing potential are required to use highly effective contraception
- Informed consent, with informed assent from capable participants
- Adequate organ function
Who cannot join
- Active bacteremia or fungemia
- History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- History or clinical evidence of any medical or social issues likely to put the participant at additional risk or to interfere with study conduct
- History of HSCT or granulocyte transfusions
- Known hypersensitivity to elements in the treatment regimen
- Undergone investigational gene therapy
- Treated with another investigational drug product within 30 days before screening
- Unable to comply with the visits and requirements of the protocol as determined by the Investigator
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Duke University
Durham, North Carolina, 27710
University of California, Los Angeles
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55454
Columbia University Irving Medical Center, Morgan Stanley Children's Hospital
New York, New York, 10032
University of Utah, Primary Children's Hospital
Salt Lake City, Utah, 84113
University of California, San Francisco
San Francisco, California, 94158
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
United Kingdom1 site
University College London Hospital
London, NW1 2PG
About this study
Official title: A Phase 1/2 Open-Label, Single-Ascending-Dose Study of EN-374, a Helper-Dependent Adenoviral-Based Gene Therapy, in Participants With X-Linked Chronic Granulomatous Disease
The goal of this clinical trial is to evaluate the safety and potential efficacy of the EN-374 treatment regimen and identify a dose level for further evaluation in participants with x-linked chronic granulomatous disease.
The main questions it aims to answer are:
- safety of the EN-374 treatment regimen
- effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
Read the detailed description
Chronic granulomatous disease (CGD) is a rare primary immune deficiency disorder characterized by recurrent bacterial or fungal infections starting in infancy. The x-linked form of CGD (X-CGD) is caused by mutations in the CYBB gene.
EN-374 is a helper-dependent adenoviral (HDAd)-based gene therapy in development for the treatment of X-CGD using an in vivo approach, which is administered by IV infusion, to genetically modify hematopoietic stem cells (HSCs) to express a wild-type CYBB gene. The EN-374 treatment regimen includes HSC mobilization, immune prophylaxis, EN-374 administration, and enrichment of genetically modified HSCs.
Adult participants with X-CGD will be enrolled into the dose-escalation part of the study. Following completion of the adult cohorts, then pediatric participants will be enrolled into the dose-expansion part of the study in decreasing age cohorts from ≥ 12 and < 18 years of age, to ≥ 2 and < 12 years of age, and finally to ≥ 3 months and < 2 years of age.
- Conditions
- X-Linked Chronic Granulomatous Disease
- Being tested
- EN-374
- Keywords
- CGD, X-CGD, Chronic Granulomatous Disease, X-Linked Chronic Granulomatous Disease, Granulomatous Disease, Chronic, Genetic Therapy, Gene Therapy, in vivo Gene Therapy, Gene Addition Therapy, in vivo Gene Addition Therapy, Hematopoietic Stem Cell Gene Therapy, in vivo Hematopoietic Stem Cell Gene Therapy
- Medical subject headings
- Granulomatous Disease, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EN-374Genetic
Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment
| Study group | Role | What they receive |
|---|---|---|
| EN-374 | Experimental | Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment Receives: Genetic: EN-374 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of EN-374
Incidence rate across all age groups of:
- treatment-emergent adverse events (TEAEs)
- treatment-related TEAEs (TRAEs)
- serious adverse events (SAEs)
Measured: From start of mobilization until Month 12
Secondary outcomes (1)
Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
- Change from baseline in the percentage of dihydrorhodamine (DHR)+ neutrophils
- Change from baseline in the percentage of participants with ≥ 10%, 20%, 30%, 40%, or 50% DHR+ neutrophils
Measured: From infusion of EN-374 until Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2025
- Study start5 Aug 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for X-Linked Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ensoma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06876363
- Sponsor's protocol ID
- EN-374-101
- Status last verified
- Aug 2026
- First submitted
- 10 Mar 2025
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open-Label, Single-Ascending-Dose Study of EN-374, a Helper-Dependent Adenoviral-Based Gene Therapy, in Participants With X-Linked Chronic Granulomatous Disease
- ClinicalTrials.gov ID
- NCT06876363
- Acronym / sponsor ID
- EN-374-101
- Conditions
- X-Linked Chronic Granulomatous Disease
- Keywords
- CGD, X-CGD, Chronic Granulomatous Disease, X-Linked Chronic Granulomatous Disease, Granulomatous Disease, Chronic, Genetic Therapy, Gene Therapy, in vivo Gene Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- EnsomaIndustry (pharma, biotech, devices)
- Study start
- 5 Aug 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 14 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate the safety and potential efficacy of the EN-374 treatment regimen and identify a dose level for further evaluation in participants with x-linked chronic granulomatous disease.
The main questions it aims to answer are:
- safety of the EN-374 treatment regimen
- effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
Detailed description
Chronic granulomatous disease (CGD) is a rare primary immune deficiency disorder characterized by recurrent bacterial or fungal infections starting in infancy. The x-linked form of CGD (X-CGD) is caused by mutations in the CYBB gene.
EN-374 is a helper-dependent adenoviral (HDAd)-based gene therapy in development for the treatment of X-CGD using an in vivo approach, which is administered by IV infusion, to genetically modify hematopoietic stem cells (HSCs) to express a wild-type CYBB gene. The EN-374 treatment regimen includes HSC mobilization, immune prophylaxis, EN-374 administration, and enrichment of genetically modified HSCs.
Adult participants with X-CGD will be enrolled into the dose-escalation part of the study. Following completion of the adult cohorts, then pediatric participants will be enrolled into the dose-expansion part of the study in decreasing age cohorts from ≥ 12 and < 18 years of age, to ≥ 2 and < 12 years of age, and finally to ≥ 3 months and < 2 years of age.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EN-374 | Experimental | Genetic: EN-374Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment |
Who may qualify
- Ages
- 3 months and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Male
- ≥ 18 years of age during dose escalation, then ≥ 3 months of age during dose expansion
- Diagnosis of X-CGD with a pathogenic mutation in the CYBB gene
- History of at least 1 severe infection requiring medical intervention or chronic inflammatory disorder
- Does not have a suitable, available, and willing human leukocyte antigens (HLA)-matched (10/10) related donor
Key exclusion criteria (8 listed)
- Active bacteremia or fungemia
- History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- History or clinical evidence of any medical or social issues likely to put the participant at additional risk or to interfere with study conduct
- History of HSCT or granulocyte transfusions
- Known hypersensitivity to elements in the treatment regimen
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EN-374Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment | Genetic | EN-374 |
Primary outcome
Safety of EN-374
Time frame: From start of mobilization until Month 12
Incidence rate across all age groups of: * treatment-emergent adverse events (TEAEs) * treatment-related TEAEs (TRAEs) * serious adverse events (SAEs)
1 secondary outcome
Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
Time frame: From infusion of EN-374 until Month 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EN-374 in people with X-Linked Chronic Granulomatous Disease, run by Ensoma at 9 sites in 2 countries.
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 8 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, 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?
This study is still under way. Results are not available in the source record yet.
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?
Safety of EN-374 (time frame: From start of mobilization until Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Aug 2026.