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

Phase 1

• Conditions: Chronic Granulomatous Disease; Inflammatory Gastrointestinal Disease; Inflammatory Lung Disease; Inflammatory Skin Disease
• Interventions: Drug: XELJANZ (tofacitinib)

• Registration Number: NCT05104723
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Study Timeline

• Study First Submitted: 2021-11-02
• Study First Submitted QC: 2021-11-02
• Study First Posted: 2021-11-03
• Study Start: 2022-08-12
• Status Verified: 2024-10-01
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-03
• Primary Completion: 2026-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XELJANZ (tofacitinib)	XELJANZ (tofacitinib)	Tofacitinib is self-administered orally at 5 mg twice per day or 11 mg once per day for 3 months.

Primary Outcome Measures

Name	Time	Method
Rate of treatment-related toxicities.	Day 1 through Day 120	To assess the safety of tofacitinib during the study period in patients with CGD.
Rate of AEs	Day 1 through Day 120	To assess the safety of tofacitinib during the study period in patients with CGD.
Rate of infection.	Day 1 through Day 120	To assess the safety of tofacitinib during the study period in patients with CGD.
Incidence of serious bacterial, mycobacterial, fungal, or viral infections defined as infections that require medical assessment or hospitalization.	Day 1 through Day 120	To assess the safety of tofacitinib during the study period in patients with CGD.

Secondary Outcome Measures

Name	Time	Method
Inflammatory lung disease: 1. Change in FEV1. 2. Change in DLCO. 3.Change in CT radiography. 4. Change in 6-minute walk.	Day 90	To assess the overall clinical response for the specific inflammatory manifestations.
CGD-related IBD: 1.Change in modified HBI. 2.Change in histopathological endoscopy.	Day 90	To assess the overall clinical response for the specific inflammatory manifestations.
Skin disease: 1.Change in presence of skin flares or ulcerations by objective photography evaluation.	Day 90	To assess the overall clinical response for the specific inflammatory manifestations.
Gene expression: 1.Change in IFN gene module enrichment score derived from whole blood RNA expression data.	Day 90	To assess the biological effect of tofacitinib on IFN-induced gene expression in CGD.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States