NCT05104723

Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications

A Phase 1/2 Open-label Study to Evaluate the Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications

• Status: Enrolling By Invitation
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Background: Chronic granulomatous disease (CGD) is a disease of the immune system, which is how the body fights germs. People with CGD get infections easily and have other health problems. Some medicines to treat CGD have a lot of side effects and do not always work. Researchers want to see if a new drug can help. Objective: To see if tofacitinib is safe to use for treating chronic CGD. Eligibility: Adults aged 18 and older with CGD who have not had success with other treatments and who are enrolled on NIH study # 93-I-0119. Design: Participants will be screened with the following: Physical exam Medical history Blood, urine, and stool tests Pregnancy test, if needed An upper gastrointestinal endoscopy and/or colonoscopy, if needed for their symptoms. Tissue samples will be collected. Skin assessment, if needed Participants will repeat some screening tests at visits. Participants will complete questionnaires about their general health and how CGD affects their daily life. Photographs will be taken of their skin, if needed. They will have lung function tests, if needed. They will have a computed tomography (CT) scan of the chest, abdomen, and pelvis, if needed. A CT scan uses X-rays to create pictures of the inside of the body. Participants will gradually reduce the amount of some CGD medicines they take. Then they will take tofacitinib as a pill twice a day or once a day for 3 months. They will keep a drug diary. They will have monthly study visits. They will have a follow-up visit about 1 month after their last study drug visit. Participation will last for about 6 months.

Detailed description

Study Description: This is a phase 1/2 open-label trial to study the safety and to explore the biological efficacy of tofacitinib in patients with confirmed and symptomatic inflammatory complications (gastrointestinal \[GI\], skin, lung) related to chronic granulomatous disease (CGD). After a 3-month regimen, participants inflammatory complications will be objectively assessed. Primary Objective: To assess the safety of tofacitinib during the study period in patients with CGD. Secondary Objectives: 1. To assess the overall clinical response for the specific inflammatory manifestations. 2. To assess the biological effect of tofacitinib on interferon (IFN)-induced gene expression in CGD. Primary Endpoints: 1. Rate of infection. 2. Rate of treatment-related toxicities. 3. Rate of adverse events (AEs). 4. Incidence of serious bacterial, mycobacterial, fungal, or viral infections defined as infections that require medical assessment or hospitalization. Secondary Endpoints: CGD-related inflammatory bowel disease (IBD): 1. Change in modified Harvey-Bradshaw Index (HBI). 2. Change in histopathological endoscopy. Inflammatory lung disease: 1. Change in forced expiratory volume (FEV1). 2. Change in diffusing capacity for carbon monoxide (DLCO). 3. Change in computed tomography (CT) radiography. 4. Change in 6-minute walk. Skin disease: 1\. Change in presence of skin flares or ulcerations by objective photography evaluation. Gene expression: 1.Change in IFN gene module enrichment score derived from whole blood RNA expression data.

Conditions

• Chronic Granulomatous Disease
• Inflammatory Gastrointestinal Disease
• Inflammatory Skin Disease
• Inflammatory Lung Disease

Interventions

Type	Name	Description
DRUG	XELJANZ (tofacitinib)	The XELJANZ 5-mg tablets or 11-mg XR tablets will taken orally twice daily or once daily, respectively, in this study.

Timeline

• Start date: 2022-08-12
• Primary completion: 2027-01-01
• Completion: 2027-01-01
• First posted: 2021-11-03
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study