RECRUITING

Evaluation of Oral Tofacitinib in Children Aged 2 to 17 Years Old Suffering From Moderate to Severe Ulcerative Colitis

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Conditions

Ulcerative ColitisPediatricTofacitinib OralMayoPUCAIFlare

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study, A3921210 is designed to evaluate the efficacy, safety and pharmacokinetics (PK) of tofacitinib in pediatric participants with moderately to severely active UC. In the US and EU, patients with prior TNFi failure or intolerance will be enrolled. Outside of the US or EU, patients having had inadequate response or intolerance to oral or IV corticosteroids or azathioprine or 6-mercaptopurine or TNFi will be enrolled. All eligible participants will initially receive open label tofacitinib at a dose expected to produce equivalent systemic exposure to that observed in adults receiving 5 mg BID with the option for individual dose increase to 10 mg BID adult dose equivalent if dose escalation criteria are met. The primary objective of this study is to evaluate the efficacy of tofacitinib based on remission in pediatric participants with moderately to severely active UC. The primary endpoint is remission by central read Mayo score following 44 weeks in the maintenance phase. Remission is defined by a Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. The study Design is an open-label Phase 3 study that includes a screening period of up to 4-weeks duration, an 8-week or 16-week induction phase, a 44-week maintenance phase, and a 24-month extension phase for pediatric participants with moderately to severely active UC. Participants will have a follow-up visit 4 weeks after the last dose of study intervention and a telephone contact 8 weeks later to assess for any adverse events (AEs)/serious adverse events (SAEs). The total maximum duration of this study will be up to 180 weeks.

Official Title

OPEN-LABEL INDUCTION AND MAINTENANCE STUDY OF ORAL CP-690,550 (TOFACITINIB) IN CHILDREN WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS

Quick Facts

Study Start:2021-08-12
Study Completion:2026-12-21
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04624230

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:2 Years to 17 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD
Inclusion CriteriaExclusion Criteria
  1. * Evidence of a personally signed and dated informed consent document and assent document.
  2. * Males and females 2 to less than18 years old and weighing at least 10 kg.
  3. * Having a pathology report that confirms colonic inflammation consistent with UC with a clinical diagnosis of UC for at least 12 weeks prior to baseline, with biopsy report supporting the diagnosis of UC.
  4. * Participants diagnosed with UC at age less than 6 years old, must have had testing and be negative for monogenic disorders associated with very early onset IBD.
  5. * Moderately to severely active UC as defined (via screening colonoscopy) by a Mayo score of at least 6, with a rectal bleeding score of at least 1 and an endoscopic subscore of at least 2.
  6. * Pediatric Ulcerative Colitis Activity Index (PUCAI) score greater or equal to 35 .
  7. * No history of dysplasia or colon cancer.
  8. * No evidence or history of untreated or inadequately treated active or latent infection with Mycobacterium Tuberculosis.
  9. * For participants outside of the United States or the European Union: have had an inadequate response or been intolerant to at least one prior therapy as listed below or have a medical contraindication to such therapies:
  10. * Oral or intravenous (IV) corticosteroids;
  11. * Azathioprine or 6-mercaptopurine;
  12. * TNF inhibitors or anti integrin therapy.
  13. * For participants in the United States and the European Union: have had an inadequate response or intolerance to TNF inhibitors.
  14. * Stable doses of the following therapies for UC:
  15. * Oral 5 Aminosalicyclic acids (ASA) or sulfasalazine
  16. * Oral corticosteroids equivalent to prednisone at most 1 mg/kg up to a maximum of 20 mg/day or budesonide up to 9 mg/day.
  17. * female participant is eligible if she is not pregnant or breastfeeding, If she is a woman of child bearing potential, she needs to be using a contraceptive method that is highly effective (with a failure rate of \<1% per year).
  1. * Diagnosis of indeterminate colitis, isolated proctitis, microscopic colitis, infectious colitis, Crohn's disease, or clinical findings suggestive of Crohn's disease.
  2. * History of symptomatic obstructive intestinal strictures or active ostomy, or history of colectomy, extensive small bowel resection ( greater than100 centimetres) or short bowel syndrome, or hospitalization for UC related reason(s) within 2 weeks of baseline visit.
  3. * 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.
  4. * Participants who have previously received tofacitinib or another Janus Kinase inhibitor.
  5. * Vaccination or exposure to a live or attenuated vaccine within the 6 weeks prior to the first dose of study drug, or who are expected to be vaccinated or to have household exposure to these vaccines during treatment or during the 6 weeks following discontinuation of study drug.
  6. * Participants having received azathioprine, 6-mercaptopurine, methotrexate, thioguanine, infliximab, adalimumab, golimumab, ustekinumab, interferon, cyclosporine, mycophenolate, tacrolimus, IV or rectally administered corticosteroids, natalizumab, vedolizumab, other antiadhesion molecules, or investigational drugs during the specified time periods prior to baseline whereby they may still have pharmacokinetic and/or pharmacodynamic effect in the body of the participant.
  7. * Previous treatment by leukocyte apheresis including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
  8. * Treatment by specified prohibited concomitant medications, including moderate to potent CYP3A inducers or inhibitors in the specified time periods prior to the first dose of study drug or are expected to receive any of these medications during the study period.
  9. * Chronic and frequent use of antimotility agents for control of diarrhea (ie, diphenoxylate hydrochloride with atropine sulfate or loperamide).
  10. * History of bowel surgery, including cholecystectomy within 6 months prior to baseline, history of appendectomy within 3 months prior to baseline, or significant trauma or major surgery within 4 weeks of screening visit are excluded.
  11. * Participants with the following laboratory values at screening:
  12. * Hemoglobin level lower than 9.0 g/Dl.
  13. * Absolute white blood cell (WBC) count lower than 3000/mm3.
  14. * Absolute neutrophil count lower than 1200/mm3.
  15. * Absolute lymphocyte count lower than 750/mm3.
  16. * Thrombocytopenia as defined by a platelet count lower than 100,000/mm3.
  17. * Estimated bedside Schwartz Glomerular filtration rate (GFR) lower or equal to 40 mL/min/1.73 m2.
  18. * Total bilirubin, aspartate aminostransferase (AST) or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal.
  19. * Positive stool examinations for enteric pathogens, pathogenic ova or parasites, or C. difficile toxin at screening.
  20. * Participants infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses.
  21. * History of more than one episode of HZ, a history of disseminated HZ or disseminated herpes simplex.
  22. * 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).
  23. * 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.
  24. * 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.
  25. * 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.
  26. * Participation in other studies involving investigational drug(s) within 2 months prior to study entry and/or during study participation.
  27. * 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.
  28. * 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.
  29. * History of allergies, intolerance or hypersensitivity to lactose or tofacitinib, or any other excipients of the investigational medicinal products, including placebos.

Contacts and Locations

Study Contact

Pfizer CT.gov Call Center
CONTACT
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com

Principal Investigator

Pfizer CT.gov Call Center
STUDY_DIRECTOR
Pfizer

Study Locations (Sites)

Phoenix Children's Hospital
Phoenix, Arizona, 85016
United States
Children's Hospital Los Angeles
Los Angeles, California, 90027
United States
University of California, San Francisco Benioff Children's Hospital
San Francisco, California, 94158
United States
University of California, San Francisco Pediatric Clinical Research Center (PCRC)
San Francisco, California, 94158
United States
Connecticut Children's Ambulatory Surgical Center
Farmington, Connecticut, 06032
United States
Connecticut Children's Infusion Center
Farmington, Connecticut, 06032
United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
United States
Nicklaus Children's Hospital
Miami, Florida, 33155
United States
Center for Advanced Pediatrics
Atlanta, Georgia, 30329
United States
Children's Healthcare of Atlanta - Arthur M. Blank Hospital
Atlanta, Georgia, 30329
United States
Outpatient Pediatric Research Center Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
United States
Boston Children's Hospital
Boston, Massachusetts, 02115
United States
Atlantic Children's Health-Pediatric Gastroenterology & Nutrition
Morristown, New Jersey, 07960
United States
Goryeb Children's Hospital (Endoscopy only)
Morristown, New Jersey, 07960
United States
Atlantic Health System- Morristown Medical Center (Pharmacy)
Morristown, New Jersey, 07962
United States
Northwell Health - Cohen Children's Medical Center
Lake Success, New York, 11042
United States
Northwell Health - Cohen Children's Medical Center
New Hyde Park, New York, 11040
United States
Weill Cornell Medicine - New York Presbyterian Hospital
New York, New York, 10021
United States
Mount Sinai Hospital (Investigational Drug Pharmacy)
New York, New York, 10029
United States
Mount Sinai Hospital Endoscopy Center (Endoscopy Only)
New York, New York, 10029
United States
Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai
New York, New York, 10029
United States
Columbia University Irving Medical Center
New York, New York, 10032
United States
CUIMC Research Pharmacy - Milstein Hospital (Pharmacy Only)
New York, New York, 10032
United States
Morgan Stanley Children's Hospital, CUIMC
New York, New York, 10032
United States
Duke University Health System
Durham, North Carolina, 27710
United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
United States
Buerger Center for Advanced Pediatric Care
Philadelphia, Pennsylvania, 19104
United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
United States
Roberts Center for Pediatric Research
Philadelphia, Pennsylvania, 19146
United States
Texas Children's Hospital - Clinical Research Center
Houston, Texas, 77030
United States
Texas Children's Hospital - Feigin Tower (Administrative Offices - Research Administrative Offices)
Houston, Texas, 77030
United States
Texas Children's Hospital - RRO Regulatory (Administrative Offices - Regulatory Location)
Houston, Texas, 77030
United States
Texas Children's Hospital - Wallace Tower
Houston, Texas, 77030
United States
Texas Children's Hospital
Houston, Texas, 77030
United States
Seattle Children's Hospital
Seattle, Washington, 98105
United States
Children's Wisconsin
Milwaukee, Wisconsin, 53226
United States

Collaborators and Investigators

Sponsor: Pfizer

  • Pfizer CT.gov Call Center, STUDY_DIRECTOR, Pfizer

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-08-12
Study Completion Date2026-12-21

Study Record Updates

Study Start Date2021-08-12
Study Completion Date2026-12-21

Terms related to this study

Keywords Provided by Researchers

  • Ulcerative Colitis
  • Pediatric
  • Tofacitinib Oral
  • Mayo
  • PUCAI
  • Flare

Additional Relevant MeSH Terms

  • Ulcerative Colitis