OPEN LABEL, MAINTENANCE STUDY OF ORAL TOFACITINIB IN CHILDREN WITH MODERATE TO SEVERE ULCERATIVE COLITIS

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2018-002378-30-IT
• Date of registration: 27/01/2022
• Prospective Registration: No
• Primary sponsor: PFIZER INC
• Public title: OPEN LABEL, MAINTENANCE STUDY OF ORAL TOFACITINIB IN CHILDREN WITH MODERATE TO SEVERE ULCERATIVE COLITIS
• Scientific title: OPEN-LABEL INDUCTION AND MAINTENANCE STUDY OF ORAL CP-690,550 (TOFACITINIB) IN CHILDREN WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS - -
• Date of first enrolment: 26/01/2022
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002378-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: - Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Finland, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Poland, Slovakia, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document and assent document (as appropriate) indicating that the subject or a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study.
2. Males and females 2 to <18 years old and weighing at least 10 kg at baseline.
3. Participants with a pathology report that confirms colonic inflammation consistent with UC at any time prior to enrollment, but with a clinical diagnosis of UC for at least 12 weeks prior to baseline. A
biopsy report supporting the diagnosis prior to the baseline visit must be available in the source documents. 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.
4. Participants diagnosed with UC at age less than 6 years old, must have had testing for very early onset (VEO) IBD and be negative for monogenic disorders associated with VEO IBD.
5. Participants with moderate to severe active UC as defined (via screening colonoscopy) by a total Mayo score of >/=6, with a rectal bleeding score of >/= 1 and an endoscopic subscore (Mayo) of >/=2. Colonoscopy must be performed within 14 days of baseline visit. Endoscopic subscore will be assessed both by a Central Reader and locally.
6. Pediatric Ulcerative Colitis Activity Index (PUCAI) score >/= 35 at baseline.
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 (TB).
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;
• Anti TNF or anti-integrin therapy.
10. For participants in the US and the EU: have had an inadequate response or intolerance to TNF inhibitors.
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 subjects who are taking them at the time of enrollment):
• Oral 5 ASA or sulfasalazine for at least 4 weeks prior to baseline.
• Oral corticosteroids equivalent to prednisone 12. Participants with documented evidence from a health professional of having received 2 vaccinations for varicella zoster virus (VZV) or participants with evidence of prior exposure to VZV based on positive serological testing at screening (ie, VZV IgG Ab).
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
For full list of inclusion criteria please refer to study Protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
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.
3. History of colectomy, extensive small bowel resection (>100 cm) or short bowel syndrome. Participants hospitalized for UC related reason(s) within 4 weeks of baseline visit.
4. Any factors or clinical characteristics potentially related to the risk of venous thromboembolism (see Section 7.2.3, 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.
5. Participants who have previously received tofacitinib or another Janus Kinase inhibitor.
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.
7.Participants receiving the following treatments:
• AZA, 6 MP, methotrexate (MTX), or thioguanine within 4 weeks prior to baseline.
• Infliximab therapy within 6 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 10 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 10 weeks prior to baseline unless an undetectable serum level has been documented following the last dose of golimumab 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 14 weeks prior to baseline unless an undetectable serum level has been documented following the last dose of vedolizumab therapy prior to baseline.
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
9. Participants previously receiving leukocyte apheresis including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
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 full list of exclusion criteria please refer to study Protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Trade Name: XELJANZ -
Product Name: Tofacitinib citrate
Product Code: [CP-690, 550-10]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tofacitinib citrate
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Xeljanz
Product Name: Tofacitinib citrate
Product Code: [CP-690, 550-10]
Pharmaceutical Form: Oral solution
INN or Proposed INN: tofacitinib
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 44 in the maintenance phase

Main Objective: • To evaluate the efficacy of tofacitinib based on remission in pediatric subjects with UC.

Secondary Objective: • To evaluate the overall efficacy of tofacitinib during induction during induction, maintenance and extension.
• To evaluate the effect of tofacitinib on biomarkers.
• To evaluate tofacitinib PK during induction and maintenance.
• To evaluate taste acceptability of tofacitinib oral solution, and/or acceptability of tofacitinib film coated tablet, if applicable, at Week 2 of the open label induction phase.

Primary end point(s): • Remission by central read Mayo score following 44 weeks in the maintenance phase.

Secondary Outcome(s)

Secondary end point(s): • response by Mayo score (Induction Week 8, Induction Week 16, Maintenance Week 44).
• Remission by Mayo score with local and central read (induction Week 8, induction Week 16), and with local read (maintenance week 44).
• Change from baseline in Mayo score (induction Week 8, induction Week 16, maintenance Week 44).
• Partial Mayo Score response over time.
• Change from baseline in Partial Mayo scores over time.
• Response/remission by PUCAI score over time.
• Change from baseline in PUCAI score over time.
• Endoscopic improvement (previously known as mucosal healing) (induction Week 8, induction Week 16, maintenance Week 44).
• Endoscopic remission (induction Week 8, induction Week 16, maintenance Week 44).
• Remission at maintenance week 44 (Mayo and PUCAI) and extension (PUCAI only) amongst participants who achieved remission at the end of Induction. Rectal bleeding subscore of 0 over time.
• Time to flare (maintenance, extension)
• Change from baseline in fecal calprotectin levels over time.
• Change from baseline in high sensitivity C-reactiveprotein (hsCRP) levels over time.
• Corticosteroid free remission Corticosteroid free remission by Partial Mayo Score over time.
• Change from baseline in lymphocyte subset counts (induction Week 8, induction Week 16, maintenance Week 44; extension Month 24).
• PK: plasma concentrations (baseline, induction Week 8, induction Week 16, maintenance Week 16, maintenance Week 44).
• Evaluation of taste acceptability of tofacitinib oral solution, and acceptability of film-coated tablet, if applicable, (Week 2).

Timepoint(s) of evaluation of this end point: Various timepoint for each secondary endpoint are defined within the endpoint

Secondary ID(s)

2018-002378-30-SE

A3921210

Ethics review

Status: Approved
Approval date: 26/01/2022
Contact: