Tofacitinib for Chronic Granulomatous Disease

Overseen By Christa S Zerbe, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: NSAIDs, Strong CYP3A4 inducers

Disqualifiers: Tuberculosis, Hepatitis B/C, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests tofacitinib, a new medication, to determine if it can safely treat chronic granulomatous disease (CGD), a condition where the immune system struggles to fight infections. People with CGD often experience frequent infections and may not respond well to current treatments. The trial aims to offer a new option for those who haven't found success with other medicines. It seeks adults with CGD who are part of another NIH study but whose symptoms remain poorly controlled by their current treatment. Participants will take tofacitinib pills for three months and undergo regular health check-ups. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

Participants will need to gradually reduce the amount of some CGD medicines they take before starting tofacitinib. If you are using acetylsalicylic acid, NSAIDs, or strong CYP3A4 inducers, you may need to stop them before joining the trial.

Is there any evidence suggesting that tofacitinib is likely to be safe for humans?

Research has shown that tofacitinib has been studied for conditions like rheumatoid arthritis (RA). These studies found that while tofacitinib can be effective, it also carries some risks. Specifically, reports have indicated serious heart problems and a higher risk of cancer in some patients.

Despite these risks, many people with RA have used tofacitinib long-term, and safety results have remained consistent. This consistency suggests that while risks exist, they are known and can be monitored. The drug's approval for RA indicates thorough safety testing in humans.

Researchers are now studying tofacitinib for chronic granulomatous disease (CGD) to assess its safety and effectiveness. Since this trial is in its early stages, the safety of tofacitinib for CGD is under careful scrutiny. Participants will be closely monitored to detect any potential side effects early. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tofacitinib is unique because it targets the JAK-STAT pathway, which plays a crucial role in immune system regulation. Unlike existing treatments for Chronic Granulomatous Disease (CGD), which primarily focus on managing infections and inflammation, tofacitinib offers a new approach by specifically inhibiting certain enzymes involved in the immune response. Researchers are excited about this treatment because it could potentially address the underlying immune dysfunction in CGD, offering a more targeted and effective solution compared to the current standard of care.

What evidence suggests that tofacitinib might be an effective treatment for chronic granulomatous disease?

Studies have shown that tofacitinib can help treat various immune system conditions. For instance, large studies on rheumatoid arthritis found that tofacitinib helped many patients manage their symptoms. In a separate study on granuloma annulare, a skin condition, three out of five patients experienced complete skin clearance after six months of treatment. Another report indicated that patients with a different immune-related condition responded well and could reduce their use of other medications, such as steroids. These findings suggest that tofacitinib, which participants in this trial will receive, might help treat chronic granulomatous disease by supporting the immune system and reducing inflammation. ^{1 6 7 8 9}

Who Is on the Research Team?

Christa S Zerbe, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Adults over 18 with Chronic Granulomatous Disease (CGD) who've had little success with other treatments can join this trial. They must be part of NIH study #93-I-0119, not have severe kidney disease or infections like hepatitis B/C, HIV, or active EBV. Pregnant individuals and those using certain drugs are excluded.

Inclusion Criteria

Participants who can become pregnant or impregnate their partner must agree to use at least one highly effective method of contraception

I have IBD, lung, or skin disease related to CGD diagnosed through endoscopy, imaging, or PFTs.

Able to provide informed consent

Exclusion Criteria

Your blood tests show very high levels of certain enzymes, or very low levels of white blood cells.

I do not have any health conditions that could affect the study's treatment evaluation.

I currently use inhaled tobacco, vaping products, cannabis, or other illicit drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1-2 visits (in-person)

Treatment

Participants take tofacitinib orally at 5 mg twice per day or 11 mg once per day for 3 months

12 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tofacitinib

Trial Overview The trial is testing Tofacitinib's safety and effectiveness for treating CGD complications. Participants will reduce current CGD meds and take Tofacitinib pills twice daily for three months while undergoing health assessments, including blood tests and CT scans.

How Is the Trial Designed?

Group I: XELJANZ (tofacitinib) Experimental Treatment 1 Intervention

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

Tofacitinib is already approved in United States, European Union for the following indications:

Approved in United States as Xeljanz for:

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Ankylosing Spondylitis
• Polyarticular Course Juvenile Idiopathic Arthritis

Approved in European Union as Xeljanz for:

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Ankylosing Spondylitis

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Tofacitinib is an effective treatment for moderate to severe rheumatoid arthritis (RA), showing significant improvements in symptoms and quality of life in clinical studies lasting up to 96 months, whether used alone or in combination with other DMARDs.

The medication is generally well tolerated, with most side effects being mild to moderate, although there is a higher incidence of herpes zoster compared to the general RA population, indicating that while manageable, monitoring for infections is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Rheumatoid Arthritis. Dhillon, S.[2022]

Tofacitinib is the first JAK inhibitor approved for treating rheumatoid arthritis (RA) and works by selectively inhibiting JAKs, which play a key role in inflammatory processes related to the disease.

In large clinical trials, tofacitinib was found to be effective and generally well tolerated for adult patients with moderately to severely active RA who did not respond adequately to previous treatments, including methotrexate and other DMARDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib: a review of its use in adult patients with rheumatoid arthritis. Scott, LJ.[2022]

Tofacitinib (Xeljanz®) is an effective oral treatment for rheumatoid arthritis (RA), showing significant improvements in symptoms and quality of life compared to placebo, as demonstrated in Phase III clinical trials.

While tofacitinib has a generally acceptable safety profile, it can lead to serious adverse effects such as infections and cardiovascular events, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib. Kawalec, P., Śladowska, K., Malinowska-Lipień, I., et al.[2020]

Tofacitinib (Xeljanz) is an effective treatment for rheumatoid arthritis (RA), showing comparable efficacy to adalimumab and improving disease control when used alone or with methotrexate.

While tofacitinib can reduce structural damage in RA, it carries risks of side effects such as upper respiratory infections and tuberculosis, necessitating careful monitoring of blood counts, lipids, and organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A new therapeutical option for chronic inflammation in rheumatology: janus kinases inhibitors (JAK)]. Varisco, PA., So, A.[2014]

Tofacitinib, an oral JAK inhibitor, demonstrated bioequivalence to Xeljanz® in a phase I trial involving 32 healthy Chinese subjects, with pharmacokinetic parameters such as peak concentration and area under the curve falling within the acceptable range of 80-125%.

The safety profile of tofacitinib was found to be comparable to that of Xeljanz®, supporting its potential for clinical use in treating inflammatory and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, crossover, phase I clinical study to evaluate bioequivalence and safety of tofacitinib and Xeljanz® in Chinese healthy subjects. Xu, Z., Wang, Y., Liu, Z., et al.[2022]

In a 12-month phase 3 trial with 717 rheumatoid arthritis patients, tofacitinib (5 mg and 10 mg doses) showed significantly higher efficacy compared to placebo, with ACR 20 response rates of 51.5% and 52.6%, respectively, indicating effective improvement in symptoms.

Tofacitinib was found to have a higher incidence of adverse events compared to placebo, including cases of pulmonary tuberculosis and changes in cholesterol and neutrophil levels, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. van Vollenhoven, RF., Fleischmann, R., Cohen, S., et al.[2022]

Citations

1. jrheum.org jrheum.org/content/50/8/1088

Response to Treatment With Tofacitinib in 11 Patients ... The findings presented in this series of 11 patients suggest that TOF may be effective and glucocorticoid-sparing in some patients with refractory GPA and ...

2. ijdvl.com ijdvl.com/therapeutic-success-of-tofacitinib-in-granuloma-annulare-a-retrospective-case-series-of-15-patients/

Therapeutic success of tofacitinib in granuloma annulare observed that three out of five patients achieved complete resolution of lesions and two had partial resolution at 6 months of treatment with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05104723

NCT05104723 | Safety and Efficacy of Tofacitinib for ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8375329/

Improvement of granulomatous skin conditions with tofacitinib ... In two recent single-case reports, treatment of GA with 2% topical tofacitinib BID resulted in near complete resolution after 12–15 weeks.

5. withpower.com withpower.com/trial/phase-2-granuloma-10-2021-e4c86

Tofacitinib for Chronic Granulomatous Disease In large clinical trials, tofacitinib was found to be effective and generally well tolerated for adult patients with moderately to severely active RA who did ...

6. xeljanz.com xeljanz.com/ra/

Home Page | XELJANZ® (tofacitinib) For RA | Safety Info XELJANZ is used to treat adults with moderately to severely active rheumatoid arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers ...

7. fda.gov fda.gov/drugs/drug-safety-and-availability/initial-safety-trial-results-find-increased-risk-serious-heart-related-problems-and-cancer-arthritis

Serious heart problems and cancer with Xeljanz (tofacitinib) Preliminary safety trial results show an increased risk of serious heart-related problems and cancer with Xeljanz, Xeljanz XR (tofacitinib).

8. academic.oup.com academic.oup.com/mr/article/34/2/272/7218392

Six-month safety and effectiveness of tofacitinib in patients ... In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7722371/

Long-term safety of tofacitinib up to 9.5 years An integrated analysis of the long-term safety of tofacitinib in patients with RA was carried out in 2015, using RCT/LTE data, with up to 8.5 ...