Infection / gp91 Grans / Chronic Granulomatous Disease · Phase 1 Trial

NADPH Oxidase Correction in mRNA-transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)

ClinicalTrials.gov · September 4, 2026

Preliminary Why this matters to you Expert discussion

Early or partial results. Treat as a signal, not a conclusion.

AI Summary

This is an active Phase 1 trial registration for an mRNA-based therapy delivering corrected gp91phox instructions to granulocytes in males aged 18–75 with chronic granulomatous disease. No results are posted; the study focuses on feasibility, maximum tolerated dose, and safety over 3 months of follow-up.

What was studied

Phase 1, Interventional, Sequential, Open label, Treatment purpose. Chronic Granulomatous Disease, Infection; Male; age from 18 Years; to 75 Years. Intervention: IV infusion of gp91-Grans at dose K: 1e6 cells/kg; IV infusion of gp91-Grans at dose K+1:1e7 cells/kg; IV infusion of gp91-Grans at dose K+2: 1-5e8 cells/kg. n = 25. 1 site: United States.

Key findings

Safety

This registry record reports no efficacy or safety results; the study is recruiting and outcomes are not yet available. Primary outcomes are feasibility and safety; no clinical efficacy endpoint (e.g., infection rate, immune function restoration) is specified.

Who this may help

The source did not state who this applies to in practice.

Plain-language summary

Phase 1 study of an mRNA-based cell therapy in chronic granulomatous disease with feasibility and safety as primary outcomes; no results reported in this registry record.

Study design

As stated by the source record.

MethodsPrimary outcome measures: Feasibility: Recruitment, implementation, and manufacturing of gp91-Grans for infusions. (assessed at 3 months); MTD determination based on the rate of AEs. MTD is defined as the highest dose level that does not cause the same grade 3 or 4 AEs in 3 or more patients (assessed at 3 months); Safety: Frequency of grade 3 or greater adverse events or serious adverse events related to the study agent (assessed at 3 months)

DesignPhase 1, Interventional, Sequential, Open label, Treatment purpose

PopulationChronic Granulomatous Disease, Infection; Male; age from 18 Years; to 75 Years

Sample size25

InterventionIV infusion of gp91-Grans at dose K: 1e6 cells/kg; IV infusion of gp91-Grans at dose K+1:1e7 cells/kg; IV infusion of gp91-Grans at dose K+2: 1-5e8 cells/kg

Setting1 site: United States

Reported figures

Quoted from the source exactly as published.

Planned enrollment25

PhasePhase 1

Primary outcome timeframe3 months

MTD definitionhighest dose level that does not cause the same grade 3 or 4 AEs in 3 or more patients

Safety endpointFrequency of grade 3 or greater adverse events or serious adverse events related to the study agent

Caveats

This registry record reports no efficacy or safety results; the study is recruiting and outcomes are not yet available.
Primary outcomes are feasibility and safety; no clinical efficacy endpoint (e.g., infection rate, immune function restoration) is specified.
Small sample size (n=25) limits generalizability and power for safety signal detection.
Follow-up duration is 3 months; long-term durability of mRNA-transfected cell effect is unknown.

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

moderate

Phase 1 design with planned dose escalation and MTD determination is appropriate for safety.

Directness

strong

Directly tests the proposed mRNA-transfected cell therapy in the target population with CGD.

Consistency

insufficient

No results reported; consistency cannot be assessed from a registry record.

Risk of bias

insufficient

No results or methods detail on blinding, allocation concealment, or endpoint adjudication reported.

Sample adequacy

limited

Estimated 25 participants is typical for Phase 1 dose escalation but underpowered for efficacy.

What is missing. This record has no key findings. That is a gap in the analysis, not a judgement about the study.

Source abstract

Registry record from ClinicalTrials.gov (NCT05189925). This is a study registration, not published results. Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID). Recruitment status: RECRUITING. Phase: PHASE1. Study type: INTERVENTIONAL. Enrollment: 25 participants (ESTIMATED). Conditions: Chronic Granulomatous Disease, Infection. Interventions: BIOLOGICAL: gp91 Grans. Primary outcome measures: Feasibility: Recruitment, implementation, and manufacturing of gp91-Grans for infusions. , 3 months; MTD determination based on the rate of AEs. MTD is defined as the highest dose level that does not cause the same grade 3 or 4 AEs in 3 or more patients , 3 months; Safety: Frequency of grade 3 or greater adverse events or serious adverse events related to the study agent , 3 months. Brief summary: Background: CGD is caused by a gene mutation. For people with CGD, their cells cannot kill germs well, so they can get frequent or life-threatening infections. Researchers want to see if a new procedure can help a person s cells kill germs for a short time. It uses messenger RNA (mRNA) to deliver correct instructions for the gene mutation to the cells. Objective: To test a procedure in which mRNA is added to a person s blood cells. Eligibility: Males aged 18-75 with CGD with a mutation in the gene that makes the protein gp91phox. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Swab to test for strep throat Some screening tests will be repeated during the study. Participants will be admitted to the NIH Clinical Center hospital for at least 7 days. They will have apheresis. For this, a medicine is injected under their skin to prepare their white blood cells for collection. An IV line is placed into an arm vein. Blood goes through the IV line into a machine that divides whole blood into red blood cells, plasma, and white blood cells. The white blood cells are removed, and the rest of the blood is returned to the participant through an IV line in their other arm. The next day, they will get their mRNA-corrected cells via IV. They will be monitored for 3 more days. After discharge, participants will keep a symptom diary. They will be contacted weekly for one month, and then once a month. They will have a follow-up visit 3 months after the infusion....

Follow from this

Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.

InfectionNational Institute of Allergy and Infectious Diseases (NIAID)gp91 GransChronic Granulomatous DiseaseNCT05189925