Chronic Granulomatous DiseasePhase 1/2NCT05104723
Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications
A Phase 1/2 study testing XELJANZ (tofacitinib) in people with Chronic Granulomatous Disease and Inflammatory Gastrointestinal Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Chronic Granulomatous Disease, Inflammatory Gastrointestinal Disease, Inflammatory Skin Disease
- What is being tested?
- XELJANZ (tofacitinib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Aug 2022to 4 May 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 27Show fewer
- 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.
- Current use of strong CYP3A4 inducer and unable to discontinue at least 14 days before beginning of tofacitinib regimen.
- Concomitant medical condition that could interfere with study drug evaluation or that is a contraindication to the proposed investigational treatment based upon known agent safety profile or toxicities.
- Any of the following laboratory abnormalities:
- Alkaline phosphatase and either ALT or AST >2.5 times the upper limit of normal (ULN).
- Serum creatinine level >5 mg/dL.
- Absolute neutrophil count (ANC) <1000 cells/microL.
- Lymphocyte count <500 cells/microL.
- History of unprovoked deep vein thrombosis, pulmonary embolism, or other thrombotic events.
- History of heart failure.
- Current immobilization, ie, bed-bound and unable to ambulate.
- Exposure to any investigational agent within the last 4 weeks.
- Any other finding that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant s ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase 1/2 Open-label Study to Evaluate the Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications
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.
Read more
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....
Read the 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:
- To assess the overall clinical response for the specific inflammatory manifestations.
- To assess the biological effect of tofacitinib on interferon (IFN)-induced gene expression in CGD.
Primary Endpoints:
- Rate of infection.
- Rate of treatment-related toxicities.
- Rate of adverse events (AEs).
- 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):
- Change in modified Harvey-Bradshaw Index (HBI).
- Change in histopathological endoscopy.
Inflammatory lung disease:
- Change in forced expiratory volume (FEV1).
- Change in diffusing capacity for carbon monoxide (DLCO).
- Change in computed tomography (CT) radiography.
- Change in 6-minute walk.
Skin disease:
- 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
- Being tested
- XELJANZ (tofacitinib)
- Keywords
- Inflammatory Bowel Disease, Interferon (IFN)-induced gene expression, JAK Inhibitor, Ulcerative Colitis, Inflammatory skin/ lung disease
- Medical subject headings
- Granulomatous Disease, Chronic, Dermatitis, Inflammatory Bowel Diseases, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| XELJANZ (tofacitinib) | Experimental | Tofacitinib is self-administered orally at 5 mg twice per day or 11 mg once per day for 3 months. Receives: Drug: XELJANZ (tofacitinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of treatment-related toxicities.
To assess the safety of tofacitinib during the study period in patients with CGD.
Measured: Day 1 through Day 120
Rate of infection.
To assess the safety of tofacitinib during the study period in patients with CGD.
Measured: Day 1 through Day 120
Rate of AEs
To assess the safety of tofacitinib during the study period in patients with CGD.
Measured: 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.
Measured: Day 1 through Day 120
Secondary outcomes (4)
CGD-related IBD: 1.Change in modified HBI. 2.Change in histopathological endoscopy.
To assess the overall clinical response for the specific inflammatory manifestations.
Measured: Day 90
Skin disease: 1.Change in presence of skin flares or ulcerations by objective photography evaluation.
To assess the overall clinical response for the specific inflammatory manifestations.
Measured: Day 90
Inflammatory lung disease: 1. Change in FEV1. 2. Change in DLCO. 3.Change in CT radiography. 4. Change in 6-minute walk.
To assess the overall clinical response for the specific inflammatory manifestations.
Measured: Day 90
Gene expression: 1.Change in IFN gene module enrichment score derived from whole blood RNA expression data.
To assess the biological effect of tofacitinib on IFN-induced gene expression in CGD.
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2021
- Study start12 Aug 2022
- Primary completion4 May 2026
- Study completion4 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christa S Zerbe, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05104723
- Sponsor's protocol ID
- 10000064
- Other IDs
- 000064-I
- Status last verified
- 5 May 2026
- First submitted
- 2 Nov 2021
- Last updated
- 7 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 28209624Henrickson 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.
PubMed 29746679
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open-label Study to Evaluate the Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications
- ClinicalTrials.gov ID
- NCT05104723
- Acronym / sponsor ID
- 10000064
- Conditions
- Chronic Granulomatous Disease, Inflammatory Gastrointestinal Disease, Inflammatory Skin Disease, Inflammatory Lung Disease
- Keywords
- Inflammatory Bowel Disease, Interferon (IFN)-induced gene expression, JAK Inhibitor, Ulcerative Colitis, Inflammatory skin/ lung disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 12 Aug 2022 (actual)
- Primary completion
- 4 May 2026 (actual)
- Study completion
- 4 May 2026 (actual)
- First posted
- 3 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To assess the overall clinical response for the specific inflammatory manifestations.
- To assess the biological effect of tofacitinib on interferon (IFN)-induced gene expression in CGD.
Primary Endpoints:
- Rate of infection.
- Rate of treatment-related toxicities.
- Rate of adverse events (AEs).
- 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):
- Change in modified Harvey-Bradshaw Index (HBI).
- Change in histopathological endoscopy.
Inflammatory lung disease:
- Change in forced expiratory volume (FEV1).
- Change in diffusing capacity for carbon monoxide (DLCO).
- Change in computed tomography (CT) radiography.
- Change in 6-minute walk.
Skin disease:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| XELJANZ (tofacitinib) | Experimental | Drug: XELJANZ (tofacitinib)Tofacitinib is self-administered orally at 5 mg twice per day or 11 mg once per day for 3 months. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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):
- Able to provide informed consent.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XELJANZ (tofacitinib)The XELJANZ 5-mg tablets or 11-mg XR tablets will taken orally twice daily or once daily, respectively, in this study. | Drug | XELJANZ (tofacitinib) |
Primary outcome
Rate of treatment-related toxicities.
Time frame: Day 1 through Day 120
To assess the safety of tofacitinib during the study period in patients with CGD.
Rate of infection.
Time frame: Day 1 through Day 120
To assess the safety of tofacitinib during the study period in patients with CGD.
Rate of AEs
Time frame: 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.
Time frame: Day 1 through Day 120
To assess the safety of tofacitinib during the study period in patients with CGD.
4 secondary outcomes
CGD-related IBD: 1.Change in modified HBI. 2.Change in histopathological endoscopy.
Time frame: Day 90
Skin disease: 1.Change in presence of skin flares or ulcerations by objective photography evaluation.
Time frame: Day 90
Inflammatory lung disease: 1. Change in FEV1. 2. Change in DLCO. 3.Change in CT radiography. 4. Change in 6-minute walk.
Time frame: Day 90
Gene expression: 1.Change in IFN gene module enrichment score derived from whole blood RNA expression data.
Time frame: Day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Background: PubMed 28209624Panes 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.
- Background: PubMed 29746679Henrickson 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christa S Zerbe, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing XELJANZ (tofacitinib) in people with Chronic Granulomatous Disease and Inflammatory Gastrointestinal Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of treatment-related toxicities. (time frame: Day 1 through Day 120). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05104723, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.