Oral Tofacitinib for Ulcerative Colitis in Children

Recruiting at 121 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: CYP3A inducers, inhibitors

Disqualifiers: Crohn's disease, HIV, Hepatitis B, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well the drug tofacitinib works for children with moderate to severe ulcerative colitis (UC), a condition that inflames the colon. The goal is to determine if the drug can achieve remission, meaning a significant reduction or disappearance of symptoms, over 44 weeks. Children who have struggled with or cannot tolerate other common UC treatments might be suitable candidates. Participants will start with a dose similar to what adults receive, with the possibility of increasing it if needed. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment option.

Will I have to stop taking my current medications?

The trial allows participants to stay on stable doses of certain medications for ulcerative colitis, like oral 5-aminosalicylic acids or sulfasalazine, and oral corticosteroids up to specified limits. However, some medications must be stopped before joining the trial, such as azathioprine, 6-mercaptopurine, and certain other drugs, as they may still affect the body.

Is there any evidence suggesting that tofacitinib is likely to be safe for children with ulcerative colitis?

Research has shown that tofacitinib has been used safely in children with ulcerative colitis (UC). In previous studies, many children tolerated tofacitinib well. However, like any medicine, side effects can occur. Some children might experience infections or other issues. Tofacitinib is already approved for adults with UC, indicating that its safety has been well-studied. While this doesn't guarantee safety for every child, it provides some confidence in its use. Always consult a doctor about the possible risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Tofacitinib is unique because it offers a new approach to treating ulcerative colitis in children by targeting the Janus kinase (JAK) pathway. This is different from many standard treatments like corticosteroids, aminosalicylates, or biologics, which have varying mechanisms of action. By focusing on the JAK pathway, tofacitinib can potentially reduce inflammation more effectively and quickly. Researchers are particularly excited about its oral administration, which is more convenient compared to injectable biologics, enhancing patient compliance and comfort.

What evidence suggests that tofacitinib might be an effective treatment for ulcerative colitis in children?

Studies have shown that tofacitinib can help treat ulcerative colitis (UC). In one study, 18% of patients with UC experienced mild or no symptoms after taking tofacitinib 10 mg twice daily for eight weeks. This treatment has also benefited patients with difficult-to-treat UC, with at least 16% showing improvement by week 8. Research indicates that tofacitinib is effective and safe for adults, supported by both clinical trials and real-world data. The treatment targets inflammation in the gut, a major issue in UC. Participants in this trial will receive tofacitinib, with dosing adjusted based on weight and specific criteria for dose escalation. ^{1 2 4 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Children aged 2-17 with moderate to severe ulcerative colitis (UC) can join this trial. They must weigh at least 10 kg and have a confirmed UC diagnosis for over 12 weeks, with specific test results showing active disease. Those who've had certain treatments or surgeries recently, live vaccines, or have other health issues like infections or low blood counts cannot participate.

Inclusion Criteria

I have never had colon cancer or precancerous colon conditions.

I do not have an untreated or poorly treated TB infection.

My ulcerative colitis is moderate to severe, confirmed by a colonoscopy.

Exclusion Criteria

I have had major bowel surgery or recent hospital visits for UC.

Any factors or clinical characteristics potentially related to the risk of venous thromboembolism that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study

Participants with the following laboratory values at screening: Hemoglobin level lower than 9.0 g/Dl, Absolute white blood cell (WBC) count lower than 3000/mm3, Absolute neutrophil count lower than 1200/mm3, Absolute lymphocyte count lower than 750/mm3, Thrombocytopenia as defined by a platelet count lower than 100,000/mm3, Estimated bedside Schwartz Glomerular filtration rate (GFR) lower or equal to 40 mL/min/1.73 m2, Total bilirubin, aspartate aminostransferase (AST) or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal, Positive stool examinations for enteric pathogens, pathogenic ova or parasites, or C. difficile toxin at screening, Participants infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses, History of more than one episode of HZ, a history of disseminated HZ or disseminated herpes simplex, History or current symptoms of any lymphoproliferative disorder (eg, Epstein Barr Virus (EBV) related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of currently lymphatic disease), Clinically significant infections currently or within 3 months prior to baseline (eg, those requiring hospitalization or parenteral antimicrobial therapy or opportunistic infections), a history of any infection requiring antimicrobial therapy within 2 weeks of baseline, or a history of any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study, Any malignancies or with a history of malignancies, with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin, Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are employees of the Sponsor, including their family members, directly involved in the conduct of the study, Participation in other studies involving investigational drug(s) within 2 months prior to study entry and/or during study participation, Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study, Pregnant female participants; breastfeeding female participants; fertile female participants of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and through the telephone follow up visit, History of allergies, intolerance or hypersensitivity to lactose or tofacitinib, or any other excipients of the investigational medicinal products, including placebos.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Induction

Participants receive open-label tofacitinib to induce remission

8-16 weeks

Regular visits for monitoring and dose adjustments

Maintenance

Participants continue to receive tofacitinib to maintain remission

44 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 in-person visit, 1 telephone contact

Extension

Participants may continue treatment in a long-term extension phase

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Tofacitinib

Trial Overview The trial is testing the drug Tofacitinib in children with UC. It starts with an open-label phase where all participants get Tofacitinib; doses may increase if needed. The main goal is to see if the drug helps achieve remission after 44 weeks of treatment by checking Mayo scores.

How Is the Trial Designed?

Group I: tofacitinib Experimental Treatment 1 Intervention

Open label tofacitinib 5 mg BID weight based adult equivalent with the option for individual dose increase to 10 mg BID weight based adult equivalent for a limited time if dose escalation criteria are met, prior to returning to 5 mg BID.

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?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study of 15 children with pediatric ulcerative colitis treated with tofacitinib, 8 patients achieved clinical remission by week 8, indicating that tofacitinib can be effective for inducing remission in this population.

Failure to achieve remission by week 16 was strongly linked to the need for colectomy, highlighting the importance of early response to tofacitinib therapy in managing severe cases of ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Tofacitinib Use in an Irish Pediatric Cohort. Ryan, N., Cooper, S., Dominik, A., et al.[2023]

In a study of 1,026 patients with ulcerative colitis, tofacitinib showed a serious adverse event (SAE) incidence of 4.06 per 100 person-years, which is comparable to the 6.30 per 100 person-years in patients treated with anti-TNF inhibitors (TNFi).

No thromboembolic events were reported in the tofacitinib group, and the rates of herpes zoster and tuberculosis were similar between tofacitinib and TNFi groups, suggesting a favorable safety profile for tofacitinib in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Comparative Risk of Serious Adverse Events With Tofacitinib and TNF Inhibitors in Patients With Ulcerative Colitis: The Korean Experience as Revealed by a National Database. Seo, GH., Jung, SH.[2022]

In a real-world study of 96 patients with ulcerative colitis, tofacitinib showed significant and rapid improvement in disease activity starting as early as day 3, with a notable decline in the simple clinical colitis activity index (SCCAI).

The safety profile of tofacitinib was consistent with previous findings, with low rates of discontinuation due to adverse events, and 25% of patients achieving steroid-free remission by day 14.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting. Long, MD., Afzali, A., Fischer, M., et al.[2023]

In a phase 2 trial involving 194 adults with moderately to severely active ulcerative colitis, tofacitinib showed a significant dose-dependent improvement in clinical response and remission rates compared to placebo, with the highest dose (15 mg) achieving a clinical response in 78% of patients (P<0.001).

Tofacitinib treatment was associated with an increase in cholesterol levels and a few cases of low neutrophil counts, indicating the need for monitoring but suggesting a favorable safety profile overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. Sandborn, WJ., Ghosh, S., Panes, J., et al.[2022]

Tofacitinib is an oral medication that effectively blocks the JAK/STAT pathway, which is involved in inflammation, and has been approved for treating moderate to severe ulcerative colitis.

The efficacy and safety of tofacitinib have been validated through three phase III clinical trials and supportive real-life data, highlighting its important role in treatment strategies for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in the treatment of ulcerative colitis: efficacy and safety from clinical trials to real-world experience. D'Amico, F., Parigi, TL., Fiorino, G., et al.[2020]

Tofacitinib, a small molecule JAK inhibitor, was successfully used to treat a 13-year-old girl with severe ulcerative colitis (UC) who had not responded to other biologic therapies, leading to complete clinical and endoscopic remission.

This case suggests that tofacitinib may be a safe and effective treatment option for pediatric patients with refractory UC, potentially reducing the need for surgical interventions like proctocolectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib for a Child with Refractory Steroid-Dependent Ulcerative Colitis: A Case Report and Review of the Literature. Alajmi, R., Alabdulhadi, M., Alali, AA., et al.[2021]

Tofacitinib, a selective Janus kinase inhibitor, successfully induced and maintained remission in a 9-year-old boy with moderately active ulcerative colitis (UC) after other biologic treatments failed.

This case suggests that tofacitinib is a safe and effective treatment option for pediatric patients with UC, even those who are steroid-dependent and refractory to other biologics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Japanese pediatric patient with refractory steroid-resistant ulcerative colitis successfully treated with Tofacitinib: A case report. Kakiuchi, T., Yoshiura, M.[2023]

In a study of 21 pediatric patients with medically refractory inflammatory bowel disease (IBD), tofacitinib demonstrated a clinical response in 42.9% of subjects after 12 weeks and maintained a similar response in 41.2% at 52 weeks, indicating its potential effectiveness for young patients.

Tofacitinib was generally well-tolerated, with no significant adverse events like thrombi or zoster reactivation reported, although some patients did discontinue treatment due to refractory disease or complications, suggesting the need for further research on its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib Therapy in Children and Young Adults With Pediatric-onset Medically Refractory Inflammatory Bowel Disease. Moore, H., Dubes, L., Fusillo, S., et al.[2022]

In a long-term study of 142 patients with moderate to severe ulcerative colitis, tofacitinib maintained high efficacy, with 68.3% of patients in remission after 12 months and 50.4% still in remission after 36 months.

The safety profile of tofacitinib remained consistent over 36 months, with no new safety risks identified, indicating it is a safe long-term treatment option for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance of Remission With Tofacitinib Therapy in Patients With Ulcerative Colitis. Colombel, JF., Osterman, MT., Thorpe, AJ., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38828483/

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective ... Tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6535722/

Tofacitinib in the treatment of ulcerative colitis: efficacy and ... Its efficacy and safety have been demonstrated in three phase III clinical trials and confirmed by promising real-life data.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04624230?cond=%22Colitis%22&intr=%22Tofacitinib%22&viewType=Table&rank=4

Evaluation of Oral Tofacitinib in Children Aged 2 to 17 ... The primary endpoint is remission by central read Mayo score following 44 weeks in the maintenance phase.

4. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/xeljanz

Xeljanz | European Medicines Agency (EMA) In the first study in 614 patients with ulcerative colitis, 18% of patients treated with Xeljanz 10 mg twice a day had mild or no symptoms after eight weeks of ...

5. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer_to_present_new_data_on_xeljanz_tofacitinib_citrate_for_ulcerative_colitis_at_ueg_week_2016

Pfizer to Present New Data on XELJANZ® (Tofacitinib ... “The new data to be presented at UEG Week deepen our understanding of the efficacy and safety profile of tofacitinib in ulcerative colitis,” ...

6. asidejournals.com asidejournals.com/index.php/Gastroenterology/article/download/19/31/1131

Efficacy and Safety of Tofacitinib in Pediatric Ulcerative ... In this study, we aim to assess the efficacy and safety of Tofacitinib in treating children with ulcerative colitis.

7. ema.europa.eu ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf

Xeljanz, INN-tofacitinib citrate - EMA There are insufficient data regarding the safety profile of tofacitinib used concomitantly with any other csDMARDs. Infections. In the double-blind portion ...