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

Who is this study for? Patients with Chronic Granulomatous Disease, Infection
What treatments are being studied? gp91 Grans
Status: Recruiting
Location: See location...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1
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.

Eligibility
Participation Requirements
Sex: Male
Minimum Age: 18
Maximum Age: 75
Healthy Volunteers: f
View:

∙ 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 gp91phox-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 gp91-Grans infusion. Acceptable methods of contraception include the following:

‣ Hormonal contraception

⁃ Male or female condom

Locations
United States
Maryland
National Institutes of Health Clinical Center
RECRUITING
Bethesda
Contact Information
Primary
Joanna L Peterson
joanna.peterson@nih.gov
(301) 346-9780
Backup
Suk S De Ravin, M.D.
sderavin@mail.nih.gov
(301) 496-6772
Time Frame
Start Date: 2022-07-22
Estimated Completion Date: 2026-07-01
Participants
Target number of participants: 25
Treatments
Experimental: IV infusion of gp91-Grans at dose K: 1e6 cells/kg
Adult CGD patients without systemic infection will participate in a dose-escalation trial to identify the most effective yet safe dose of study agent. Subjects enrolled will receive 1 administration of study agent at dose K, and safety of dose will be determined.
Experimental: IV infusion of gp91-Grans at dose K+1:1e7 cells/kg
Adult CGD patients without systemic infection will participate in a dose-escalation trial to identify the most effective yet safe dose of study agent. Subjects enrolled will receive 1 administration of study agent at dose K+1, and safety of dose will be determined.
Experimental: IV infusion of gp91-Grans at dose K+2: 1-5e8 cells/kg
Adult CGD patients without systemic infection will participate in a dose-escalation trial to identify the most effective yet safe dose of study agent. Subjects enrolled will receive 1 administration of study agent at dose K+2, and safety of dose will be determined.
Related Therapeutic Areas
Sponsors
Leads: National Institute of Allergy and Infectious Diseases (NIAID)

This content was sourced from clinicaltrials.gov