EN-374 Gene Therapy for Chronic Granulomatous Disease

Recruiting at 3 trial locations

Overseen By Andrew Dietz, MD, MSCR

Age: Any Age

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Ensoma

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called EN-374 for individuals with chronic granulomatous disease (CGD), a rare immune system disorder. The researchers aim to determine if this treatment is safe and increases the production of functional neutrophils, which are crucial for fighting infections. The trial seeks male participants diagnosed with X-linked CGD who have experienced serious infections or ongoing inflammation. Participants should also have a genetic mutation in the CYBB gene and lack a suitable donor for a stem cell transplant. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that the EN-374 treatment regimen is likely to be safe for humans?

Research has shown that gene therapies like EN-374 have potential in treating conditions such as chronic granulomatous disease (CGD). In an earlier study, 6 out of 9 patients experienced positive results after 12 months, suggesting promise for CGD patients.

The FDA has approved EN-374 therapy for testing, indicating it has passed initial safety checks. However, this trial is in the early stages and primarily focuses on assessing safety. Participants might experience some side effects, and understanding these is one of the trial's main goals.

For those considering participation, it's important to know that early trials aim to determine the right dose and identify any issues. The results will help ensure the treatment is safe and effective for future use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Chronic Granulomatous Disease, which often involve long-term antibiotics or interferon-gamma therapy, EN-374 is a gene therapy administered through a single intravenous infusion. This approach aims to correct the underlying genetic defect, potentially offering a more lasting solution. Researchers are excited because EN-374 targets the root cause of the disease, rather than just managing symptoms, which could lead to a significant breakthrough in how we treat this condition.

What evidence suggests that the EN-374 treatment might be an effective treatment for chronic granulomatous disease?

Research shows that the EN-374 gene therapy is designed to help patients with X-linked chronic granulomatous disease (X-CGD), a condition that impairs white blood cells' ability to fight infections. EN-374 repairs a key protein called NADPH oxidase in more than 10% of neutrophils, a type of white blood cell. Studies indicate that this level of repair can lead to better infection outcomes. Early results suggest that this treatment could significantly enhance the immune system's ability to combat infections in patients with X-CGD. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for males with X-linked chronic granulomatous disease who lack a suitable matched donor for stem cell transplant. Participants must have had at least one severe infection or chronic inflammation, be able to consent, use effective contraception if sexually active, and have adequate organ function.

Inclusion Criteria

* 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

My test for anti-EN-374 antibodies is negative.

I am male.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mobilization

Hematopoietic stem cells (HSCs) are mobilized in preparation for gene therapy

2 weeks

Treatment

Participants receive a single dose of EN-374 administered by intravenous infusion, followed by enrichment of genetically modified HSCs

1 week

Follow-up

Participants are monitored for safety and effectiveness, including the production of functional neutrophils with NADPH oxidase activity

12 months

What Are the Treatments Tested in This Trial?

Interventions

• EN-374

Trial Overview The study tests the safety and effectiveness of EN-374 gene therapy in producing functional neutrophils in patients with x-linked chronic granulomatous disease. It also aims to determine the appropriate dose level for future studies.

How Is the Trial Designed?

Group I: EN-374 Experimental Treatment 1 Intervention

Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment

Who Is Running the Clinical Trial?

Ensoma

Lead Sponsor

Trials

6

Recruited

210+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06876363

NCT06876363 | Study of EN-374 Gene Therapy in ... 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 ...

2. ensoma.com ensoma.com/wp-content/uploads/ASH-2024-2198.pdf

EN-374 restores CYBB Expression and NADPH oxidase ... Restoring more than 10% of neutrophils with NADPH oxidase activity has been shown to confer clinically meaningful improvements in infection outcomes in patients ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7115833/

Lentiviral gene therapy for X-linked chronic granulomatous ... Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative, and recent advances have improved the results from this treatment considerably.

4. asgct.careboxhealth.com asgct.careboxhealth.com/en-US/trial/listing/587135

Study of EN-374 Gene Therapy in Participants With X ... 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 ...

5. contemporarypediatrics.com contemporarypediatrics.com/view/fda-clears-en-374-therapy-application-for-x-linked-chronic-granulomatous-disease

FDA clears EN-374 therapy application for X-linked chronic ... On May 12, 2025, the FDA cleared an investigational new drug application for Ensoma's lead program EN-374 in X-linked chronic granulomatous disease (X-CGD).

6. trialx.com trialx.com/clinical-trials/listings/321601/study-of-en-374-gene-therapy-in-participants-with-x-linked-chronic-granulomatous-disease/

Study of EN-374 Gene Therapy in Participants With X ... 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 ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/587135

Study of EN-374 Gene Therapy in Participants With X-Linked ... 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 ...