Tofacitinib for Ulcerative colitis

Inclusion criteria

• {"criterion_text":"- 1. Evidence of a personally signed and dated informed consent document and assent document indicating that the participant or a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study.\n- 10. For participants in the US and the EU: have had an inadequate response or intolerance to TNF inhibitors.\n- 11. Stable doses of the following therapies for UC for designated time and throughout study (Note: The following therapies for UC are not required, however allowed, and if taken, must remain stable for those participants who are taking them at the time of enrollment): • Oral 5-Aminosalicyclic acids (ASA) or sulfasalazine for at least 4 weeks prior to baseline. • Oral corticosteroids equivalent to prednisone ≤1 mg/kg up to a maximum of 20 mg/day or budesonide up to 9 mg/day at least 2 weeks prior to baseline.\n- 12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.\n- 13. No contraception methods are required for male participants in this study, as the calculated safety margin is ≥100 fold between the estimated maternal exposure due to seminal transfer and the no observed adverse effect level (NOAEL) for serious manifestations of developmental toxicity in nonclinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: • Is not a woman of childbearing potential (WOCBP) (see definitions in Section 4.3.4.1). OR • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), as described in Section 4.3.4.2, during the intervention period and for at least 12 weeks after the last dose of study intervention. If a highly effective method that is user dependent is chosen, a second effective method of contraception, as described in Section 4.3.4.2, must also be used. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.\n- 2. Males and females 2 to <18-years-old and weighing at least 10 kg at baseline.\n- 3. Participants with a clinical diagnosis of UC for at least 12 weeks prior to baseline and with a pathology report that confirms colonic inflammation consistent with UC at any time prior to enrollment. A biopsy report supporting the diagnosis prior to the baseline visit must be available in the source documents (can be obtained from biopsies performed at screening if prior pathology report is not available). In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided colitis, or pancolitis) based on prior endoscopy must also be available in the source documentation.\n- 4. Participants diagnosed with UC at age less than 6 years old, must have had testing for very early onset (VEO) inflammatory bowel disease (IBD) and be negative for monogenic disorders associated with VEO IBD.\n- 5. Participants with moderately to severely active UC as defined (via screening endoscopy) by a Mayo score of ≥6, with a rectal bleeding score of ≥1 and an endoscopic subscore (Mayo) of ≥2 (assessed by local read). Endoscopy must be performed within 14 days of baseline visit. If the participant had a colonoscopy with biopsies showing no dysplasia or colon cancer within 12 months prior to baseline with appropriate documentation in source, then the baseline endoscopy may be either colonoscopy (with or without random biopsies) or flexible sigmoidoscopy (with or without random biopsies). However targeted biopsies should be obtained if there are observed abnormalities or lesions of clinical concern during endoscopy. All pathology reports must be available in the source document prior to enrollment. Note: The Mayo endoscopic subscore assessed locally will be used to derive the Mayo score to determine eligibility.\n- 6. Pediatric Ulcerative Colitis Activity Index (PUCAI) score ≥35 at baseline.\n- 7. No history of dysplasia or colon cancer.\n- 8. No evidence or history of untreated or inadequately treated active or latent infection with Mycobacterium tuberculosis (TB).\n- 9. For participants outside of the US or the EU: 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: • Oral or intravenous (IV) corticosteroids; • Azathioprine or 6-MP; • TNF inhibitors or anti-integrin therapy."}

Exclusion criteria

• {"criterion_text":"- 1. Diagnosis of indeterminate colitis, isolated proctitis, microscopic colitis, infectious colitis, Crohn’s disease, or clinical findings suggestive of Crohn’s disease.\n- 10. Participants receiving prohibited concomitant medications, including moderate to potent CYP3A inducers or inhibitors (see Appendix 3) 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. • For moderate to potent CYP3A inducers, within 28 days or 5 half-lives, whichever is longer, prior to first dose of study drug. For moderate to potent CYP3A inhibitors, within 7 days or 5 half-lives, whichever is longer, prior to first dose of study drug.\n- 11. Participants who require chronic and frequent use of antimotility agents for control of diarrhea (ie, diphenoxylate hydrochloride with atropine sulfate or loperamide).\n- 12. Participants with a history of bowel surgery, including cholecystectomy within 6 months prior to baseline. Participants with appendectomy within 3 months prior to baseline are excluded.\n- 13. Participants with significant trauma or major surgery within 4 weeks of screening visit.\n- 14. Participants with the following laboratory values at screening: • Hemoglobin level <9.0 g/dL. • An absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3) or absolute neutrophil count of <1.2 x 109/L (<1200/mm3) or absolute lymphocyte count of <0.75 x 109/L (<750/mm3). • Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3). • Estimated Glomerular filtration rate (GFR) ≤40 mL/min/1.73 m2. GFR will be calculated by the Central lab using the bedside Schwartz formula (see Appendix 4). • Total bilirubin, aspartate aminostransferase (AST) or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal. Note: Participants with a history of Gilbert’s syndrome may have a direct bilirubin measured and are eligible for the study provided the direct bilirubin is ≤ upper limit of normal (ULN).\n- 15. Participants who have positive stool examinations for enteric pathogens, pathogenic ova or parasites, or C. difficile toxin at screening.\n- 2. History of symptomatic obstructive intestinal strictures or active ostomy.\n- 3. History of colectomy, extensive small bowel resection (>100 cm) or short bowel syndrome. Participants hospitalized for UC related reason(s) within 2 weeks of baseline visit other than for standard of care monitoring/observation or performing baseline endoscopic procedure.\n- 4. Any factors or clinical characteristics potentially related to the risk of venous thromboembolism (see Section 7.2.4, Risk Factor Check for VTE) 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.\n- 5. Participants who have previously received tofacitinib or another Janus Kinase inhibitor.\n- 6. Participants vaccinated or exposed 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.\n- 7. Participants receiving the following treatments: • AZA, 6MP, methotrexate (MTX), or thioguanine within 2 weeks prior to baseline. • Infliximab therapy within 2 weeks prior to baseline unless an undetectable serum level has been documented following the last dose of infliximab therapy prior to baseline. • Adalimumab therapy within 4 weeks prior to baseline unless an undetectable serum level has been documented following the last dose of adalimumab therapy prior to baseline. • Golimumab therapy within 4 weeks prior to baseline unless an undetectable serum level has been documented following the last dose of golimumab therapy prior to baseline. • Ustekinumab therapy within 6 weeks prior to baseline unless an undetectable serum level has been documented following the last dose of ustekinumab therapy prior to baseline. • Interferon therapy within 8 weeks prior to baseline. • Cyclosporine, mycophenolate, or tacrolimus within 4 weeks prior to baseline. • Intravenous (IV) corticosteroids within 2 weeks prior to baseline. • Rectally administered formulations of corticosteroids or 5-ASA within 1 week of screening endoscopy. • Natalizumab within 1 year prior to baseline. • Vedolizumab therapy within 6 weeks prior to baseline unless an undetectable serum level has been documented following the last dose of vedolizumab therapy prior to baseline.\n- 8. Investigational drugs within 3 months of baseline. Other antiadhesion molecules within 5 half-lives prior to baseline unless an undetectable serum level has been documented following the last dose of other antiadhesion molecule therapy prior to baseline.\n- 9. Participants previously receiving leukocyte apheresis including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline."}

Primary endpoints

• {"endpoint_text":"- Remission by central read Mayo score following 44 weeks in the maintenance phase.","definition_or_measurement_approach":"Remission assessed by central reading of the Mayo score at Week 44 of the maintenance phase (central read endoscopic assessment included)."}

Secondary endpoints

• {"endpoint_text":"- 1. Response by Mayo score (induction Week 8, induction Week 16, maintenance Week 44).","definition_or_measurement_approach":"Response assessed by Mayo score at induction Week 8, induction Week 16, and maintenance Week 44 (local/central reads as specified per timepoint)."}
• {"endpoint_text":"- 2. Remission by Mayo score with local and central read (induction Week 8, induction Week 16), and with local read (maintenance Week 44).","definition_or_measurement_approach":"Remission assessed by Mayo score using both local and central reads at induction Weeks 8 and 16; local read used at maintenance Week 44."}
• {"endpoint_text":"- 3. Change from baseline in Mayo score (induction Week 8, induction Week 16, maintenance Week 44).","definition_or_measurement_approach":"Change in total Mayo score from baseline measured at specified induction and maintenance timepoints."}
• {"endpoint_text":"- 4. Partial Mayo Score response over time.","definition_or_measurement_approach":"Assessment of partial Mayo score response longitudinally over study visits."}
• {"endpoint_text":"- 5. Change from baseline in partial Mayo scores over time.","definition_or_measurement_approach":"Change from baseline in partial Mayo subscores over time."}
• {"endpoint_text":"- 6. Response by PUCAI score over time.","definition_or_measurement_approach":"Response measured by Pediatric Ulcerative Colitis Activity Index (PUCAI) at serial timepoints."}
• {"endpoint_text":"- 7. Remission by PUCAI score over time.","definition_or_measurement_approach":"Remission assessed by PUCAI over time."}
• {"endpoint_text":"- 8. Change from baseline in PUCAI score over time.","definition_or_measurement_approach":"Change from baseline in PUCAI measured longitudinally."}
• {"endpoint_text":"- 9. Endoscopic improvement (previously known as mucosal healing) (induction Week 8, induction Week 16, maintenance Week 44).","definition_or_measurement_approach":"Endoscopic improvement assessed at induction Weeks 8 and 16 and maintenance Week 44 (endoscopic subscore assessments)."}
• {"endpoint_text":"- 10. Endoscopic remission (induction Week 8, induction Week 16, maintenance Week 44).","definition_or_measurement_approach":"Endoscopic remission assessed at specified induction and maintenance timepoints."}
• {"endpoint_text":"- 11. Remission at maintenance Week 44 (Mayo and PUCAI) and extension (PUCAI only) amongst participants who achieved remission at the end of Induction.","definition_or_measurement_approach":"Remission status by Mayo and PUCAI at maintenance Week 44 and PUCAI during extension in those who entered maintenance in remission."}
• {"endpoint_text":"- 12. Rectal bleeding subscore of 0 over time.","definition_or_measurement_approach":"Assessment of rectal bleeding subscore (Mayo component) equal to 0 longitudinally."}
• {"endpoint_text":"- 13. Time to flare (maintenance, extension)","definition_or_measurement_approach":"Time from maintenance entry to clinical flare during maintenance and extension phases."}
• {"endpoint_text":"- 14. Change from baseline in fecal calprotectin levels over time.","definition_or_measurement_approach":"Serial fecal calprotectin measurements compared to baseline."}
• {"endpoint_text":"- 15. Change from baseline in high sensitivity C-reactive protein (hs-CRP) levels over time.","definition_or_measurement_approach":"Serial hs-CRP laboratory measurements compared to baseline."}
• {"endpoint_text":"- 16. Corticosteroid free remission by partial Mayo Score over time.","definition_or_measurement_approach":"Assessment of corticosteroid-free remission using partial Mayo score over study visits."}
• {"endpoint_text":"- 17. Change from baseline in lymphocyte subset counts (induction Week 8, induction Week 16, maintenance Week 44; extension Month 24).","definition_or_measurement_approach":"Laboratory assessment of lymphocyte subset counts at specified timepoints (includes extension Month 24)."}
• {"endpoint_text":"- 18. PK: plasma concentrations (baseline, induction Week 8, induction Week 16, maintenance Week 16, maintenance Week 44).","definition_or_measurement_approach":"Pharmacokinetic plasma concentration sampling at listed visits/timepoints."}
• {"endpoint_text":"- 19. Evaluation of taste acceptability of tofacitinib oral solution, and acceptability of film-coated tablet, if applicable, (Week 2).","definition_or_measurement_approach":"Participant-reported acceptability/taste assessments (oral solution and tablet where applicable) at Week 2."}

Methods

• Digital adverts (online/digital advertising) targeting patients/caregivers (country-specific digital adverts files present).
• Online trial listing (online trial listing documents used to advertise trial availability).
• Advocacy group engagement (advocacy group letter and study alert materials to notify patient organisations).
• Doctor-to-patient letters and Doctor-to-Doctor letters (materials for clinicians to inform patients).
• Patient-facing printed materials: patient brochure, patient flyer, patient poster, patient visit guide, caregiver brochure, patient member letters.
• School/work letters (materials to inform schools/workplaces).
• Flare email template (email outreach to potential participants during disease flares).

Belgium

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

28-06-2024

Processing Time Days

14

Number Of Sites

4

Number Of Participants

4

Finland

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

27-06-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

16-07-2024

Processing Time Days

32

Number Of Sites

3

Number Of Participants

1

France

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

12-08-2024

Processing Time Days

59

Number Of Sites

2

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

27-06-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

3

Hungary

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

12

Number Of Sites

2

Number Of Participants

2

Sweden

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

27-06-2024

Processing Time Days

13

Number Of Sites

3

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

12

Number Of Sites

2

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

10-07-2024

Processing Time Days

26

Number Of Sites

5

Number Of Participants

14

Italy

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

03-07-2024

Processing Time Days

19

Number Of Sites

3

Number Of Participants

5

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}