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

• Register: ClinicalTrials.gov
• Last refreshed on: 14 July 2025
• Main ID: NCT05189925
• Date of registration: 12/01/2022
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: NADPH Oxidase Correction in mRNA-transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)
• Scientific title: NADPH Oxidase Correction in mRNA Transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)
• Date of first enrolment: July 22, 2022
• Target sample size: 25
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05189925
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Joanna L Peterson

• Name: Suk S De Ravin, M.D.
• Affiliation: National Institute of Allergy and Infectious Diseases (NIAID)

• Name: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Key inclusion & exclusion criteria

- 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 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

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study
participation:

- Evidence of moderate to severe systemic infections as defined by any of the
following:

- Fevers >=39 (Infinite)C within 3 days of treatment.

- Absolute neutrophil count (ANC) >12,000/microliter at screening (some CGD
patients may chronically have ANC higher than the upper limit of normal value
and not have a systemic infection).

- Standard clinical diagnosis (by any imaging technology) of pneumonia, liver
abscess, or other deep tissue abscess (other than chronic anal fissures or
fistula or superficial skin or subcutaneous infections, which are allowable for
this trial) at screening.

- Positive blood culture within 2 weeks of treatment.

- Receipt of a high-dose steroid, equivalent to >1 mg/kg/day of prednisone, within 30
days of screening. There is a high percentage of CGD patients with inflammatory
bowel disease on >0.5 mg/kg/day maintenance prednisone.

- 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 Cardiology consultation.

- Current or history of invasive cancers that require chemotherapy within 5 years of
screening.

- Evidence of urinary tract infection at screening.

- Evidence of streptococcal pharyngitis at screening.

- Active hepatitis B, C, or HIV infections at screening.

- Unstable hypertension requiring addition of new anti-hypertensives within 2 weeks of
screening.

- Impaired renal function that is unstable, with serum creatinine >3.0 mg/dL and
rising.

- Serum transaminases and bilirubin that are >3 x the upper limit of normal.

NOTE: For prospective subjects who, per PI assessment at screening, have abnormal liver
function tests, and/or a significant history of liver disease, and/or liver-related
complications of CGD, and who otherwise meet eligibility criteria [i.e. those who do NOT
meet any of the exclusion set forth herein], a hepatology consult will be required at
screening, and participation must be approved in writing by hepatology to the PI.

- Electrocardiogram abnormalities indicative of acute myocardial injury, or
arrhythmias that presents anesthetic risks, at screening.

- Anemia with hemoglobin <8 g/dL (transfusions to correct anemia permitted).

- Thrombocytopenia (platelets <50 x10^9 cells/L) (platelet transfusions to correct
thrombocytopenia permitted).

- Profound thrombocytopenia (platelet counts <10,000/microliter) that is not
reversible with platelet transfusions.

- Abnormal prothrombin time/partial thromboplastin time (PT/PTT) values outside the
ranges accepted at the NIH CC that are not corrected or that cannot be attributed to
presence of Lupus anticoagulant (commonly found in CGD patients).

- Inherited bleeding disorder that precludes line placement.

- Severe oxygen-dependent pulmonary disease that increases risks of procedures that
may require sedation.

- History of or current evidence of alcohol or illicit drug abuse or dependence.

- Participation in a clinical protocol that includes an intervention that, in the
opinion of the investigator, may affect the results of the current study.

Subjects will be selected in an equitable manner from the available pool of potentially
eligible individuals, without regard to factors such as gender, race, ethnicity,
socioeconomic status, etc, except for age and sex.


Age minimum: 18 Years
Age maximum: 75 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Infection

Chronic Granulomatous Disease

Intervention(s)

Biological: gp91 Grans

Primary Outcome(s)

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 [Time Frame: 3 months]

Safety: Frequency of grade 3 or greater adverse events or serious adverse events related to the study agent [Time Frame: 3 months]

Feasibility: Recruitment, implementation, and manufacturing of gp91-Grans for infusions. [Time Frame: 3 months]

Secondary Outcome(s)

Determine percent of circulating dihydrorhodamine (DHR) positive granulocytes following study agent infusion. [Time Frame: 3 months]

Serial measurement of circulating DHR+ granulocytes from peripheral blood until day 3 following study agent infusion or disappearance of DHR+ granulocytes. [Time Frame: 3 days]

Secondary ID(s)

220001

22-I-0001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors