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

NCT05104723 | Enrolling By Invitation Phase 1 FDA Drug

• 2 other identifiers: 10000064000064-I
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammatory Lung Disease; Inflammatory Skin Disease; Chronic Granulomatous Disease; Inflammatory Gastrointestinal Disease

Keywords

Inflammatory Bowel Disease; Interferon (IFN)-induced gene expression; JAK Inhibitor; Ulcerative Colitis; Inflammatory skin/ lung disease

Outcome Measures

Primary Outcomes (4)

• Rate of treatment-related toxicities.

  To assess the safety of tofacitinib during the study period in patients with CGD.

  Day 1 through Day 120

• Rate of infection.

  To assess the safety of tofacitinib during the study period in patients with CGD.

  Day 1 through Day 120

• Rate of AEs

  To assess the safety of tofacitinib during the study period in patients with CGD.

  Day 1 through Day 120

• Incidence of serious bacterial, mycobacterial, fungal, or viral infections defined as infections that require medical assessment or hospitalization.

  To assess the safety of tofacitinib during the study period in patients with CGD.

  Day 1 through Day 120

Secondary Outcomes (4)

• CGD-related IBD: 1.Change in modified HBI. 2.Change in histopathological endoscopy.

  Day 90

• Skin disease: 1.Change in presence of skin flares or ulcerations by objective photography evaluation.

  Day 90

• Inflammatory lung disease: 1. Change in FEV1. 2. Change in DLCO. 3.Change in CT radiography. 4. Change in 6-minute walk.

  Day 90

• Gene expression: 1.Change in IFN gene module enrichment score derived from whole blood RNA expression data.

  Day 90

Study Arms (1)

XELJANZ (tofacitinib)

EXPERIMENTAL

Tofacitinib is self-administered orally at 5 mg twice per day or 11 mg once per day for 3 months.

Drug: XELJANZ (tofacitinib)

Interventions

XELJANZ (tofacitinib) DRUG

The XELJANZ 5-mg tablets or 11-mg XR tablets will taken orally twice daily or once daily, respectively, in this study.

XELJANZ (tofacitinib)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Aged \>=18 years.
• Enrolled on NIH study 93-I-0119.
• Has a documented diagnosis of one or more of the following and is not controlled under current therapy (per investigator assessment):
• Endoscopically diagnosed mild-to-severe CGD-related IBD.
• Radiographic or PFT changes (DLCO\<60%, FEV1\<70%) consistent with CGD-related inflammatory lung disease.
• Any inflammatory skin disease related to CGD (eg, hidradenitis suppurativa or granulomatous skin disease).
• Able to provide informed consent.
• Participants who can become pregnant or who can impregnate their partner must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy, starting at the first dose of tofacitinib until 2 days after the last dose. Highly effective methods include a barrier (eg, condom, diaphragm, cervical cap), intrauterine device, or hormonal contraception.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Known allergy or hypersensitivity to any component of the tofacitinib formulation.
• Known allergy or hypersensitivity to any component of the acyclovir or valacyclovir formulation.
• Active or latent tuberculosis.
• Infection with hepatitis B or C, or HIV.
• Active EBV infection.
• History of GI perforation.
• History of malignancy (except for nonmelanoma skin cancer).
• Concomitant use of acetylsalicylic acid and/or NSAIDs that cannot be safely discontinued.
• History of connective tissue disease.
• End-stage renal disease or chronic kidney disease, defined as estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m\^2.
• Evidence of other invasive or systemic fungal, bacterial, or viral infections requiring therapy.
• Pregnant.
• Breastfeeding.
• Current use of inhaled tobacco products, vaping products, inhaled cannabis, or other illicit inhaled drugs.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Panes J, Sandborn WJ, Schreiber S, Sands BE, Vermeire S, D'Haens G, Panaccione R, Higgins PDR, Colombel JF, Feagan BG, Chan G, Moscariello M, Wang W, Niezychowski W, Marren A, Healey P, Maller E. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials. Gut. 2017 Jun;66(6):1049-1059. doi: 10.1136/gutjnl-2016-312735. Epub 2017 Feb 16.

  PMID: 28209624 BACKGROUND

• Henrickson SE, Jongco AM, Thomsen KF, Garabedian EK, Thomsen IP. Noninfectious Manifestations and Complications of Chronic Granulomatous Disease. J Pediatric Infect Dis Soc. 2018 May 9;7(suppl_1):S18-S24. doi: 10.1093/jpids/piy014.

  PMID: 29746679 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Granulomatous Disease, Chronic; Dermatitis; Inflammatory Bowel Diseases; Colitis, Ulcerative

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Study Officials

• Christa S Zerbe, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 3, 2021
• Study Start: August 12, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04-17

Locations

US (1)