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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing tofacitinib, a pill that reduces inflammation, in adults with chronic granulomatous disease (CGD) who haven't responded to other treatments. The drug aims to calm the overactive immune system in these patients. Tofacitinib has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.

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.

What data supports the effectiveness of the drug Tofacitinib for treating chronic granulomatous disease?

Tofacitinib has been shown to be effective in treating rheumatoid arthritis by reducing inflammation and improving quality of life in patients who did not respond well to other treatments. It works by inhibiting certain pathways in the immune system, which may suggest potential benefits for other inflammatory conditions. ^{1 2 3 4 5}

What is the safety profile of Tofacitinib in humans?

Tofacitinib, used for conditions like rheumatoid arthritis, has been generally well tolerated in clinical trials, but it can cause side effects such as infections (including tuberculosis and herpes zoster), changes in blood counts, and cardiovascular events. Regular monitoring of blood pressure, kidney and liver function, and blood counts is recommended during treatment. ^{1 2 3 4 6}

How does the drug tofacitinib differ from other treatments for chronic granulomatous disease?

Tofacitinib is unique because it is an oral drug that inhibits Janus kinase (JAK), a key player in immune system signaling, which is different from many existing treatments that are often injected or infused. This mechanism allows it to modulate immune responses, offering a novel approach for conditions like chronic granulomatous disease, where standard treatments may not be well established. ^{1 2 3 4 6}

Research Team

Christa S Zerbe, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Netherlands 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. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Rheumatoid Arthritis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib. [2020]