NADPH Oxidase Correction in mRNA Transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)
National Institute of Allergy and Infectious Diseases (NIAID)
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.
Description
Study Design: This is a phase 1, open-label, dose-escalation trial to assess the safety and feasibility of administering CGD-Grans to adult patients with X-linked CGD and to identify the maximum tolerated dose (MTD). Subjects will undergo granulocyte-enriched apheresis to provide cell product for mRNA-correction and then receive 1 administration of study agent. The first subjects enrolled will receive the study agent at the lowest dose, and when a level has been determined to be safe, the dose level will be increased to a second and then third dose level for subsequent subjects.Subjects will…
Eligibility
- Age range
- 18–75 years
- Sex
- Male
- Healthy volunteers
- No
* 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 contra…
Interventions
- Biologicalgp91 Grans
Adults with gp91phox-deficient CGD without systemic infection will participate in a dose escalation trial to identify the MTD (the most effective yet safe dose) of gp91 Grans IV infusion.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland