RecruitingPhase 1

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

United States25 participantsStarted 2022-07-22

Plain-language 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.

Who can participate

Age range18 Years – 75 Years

SexMALE

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

* INCLUSION CRITERIA: Individuals must meet all of the following criteria to be eligible for study participation: * Males aged 18 to 75 years * CGD confirmed by DHR and deficiency subtype confirmed by protein analysis and/or genetic sequencing * Has a physician at home for follow-up care * Able to provide informed consent * For men who engage in activities that can result in pregnancy, agree to use contraception when engaging in sexual activities that can result in pregnancy. Contraception must be used from screening through 3 months after the CGD-Grans infusion. Acceptable methods of contraception include the following: * Hormonal contraception * Male or female condom EXCLUSION CRITERIA: Individuals meeting any of the following criteria will be excluded from study participation: * Clinically unstable due to moderate to severe acute systemic infections as defined by persistent resting tachypnea, tachycardia, or hypoxia of \>20% from baseline and hypotension. * Current or history of stage 4 chronic kidney disease or estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73 m\^2 within 90 days of baseline. * Unstable diabetes mellitus with hemoglobin A1c \>7.0% and fasting serum glucose \>200 mg/dL at screening. * Current or history of heart failure stage D as defined by the American College of Cardiology Foundation/American Heart Association guidelines. * History of arrhythmias that are symptomatic and deemed clinically unsafe for participation by NIH CC Cardiol…

What they're measuring

Feasibility: Recruitment, implementation, and manufacturing of gp91-Grans for infusions.

Timeframe: 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

Timeframe: 3 months

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

Timeframe: 3 months

Trial details

NCT IDNCT05189925

SponsorNational Institute of Allergy and Infectious Diseases (NIAID)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2026-07-01

Contact for this trial

Joanna L Peterson

(301) 346-9780 joanna.peterson@nih.gov

View on ClinicalTrials.gov More Chronic Granulomatous Disease trials

Plain-language summary

Who can participate

Age range18 Years – 75 Years

SexMALE

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Feasibility: Recruitment, implementation, and manufacturing of gp91-Grans for infusions.

Timeframe: 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

Timeframe: 3 months

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

Timeframe: 3 months