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

NCT04624230

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Ulcerative Colitis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
2-17 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Evidence of a personally signed and dated informed consent document and assent document.

- Males and females 2 to less than18 years old and weighing at least 10 kg.

- 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.

- 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.

- 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.

- Pediatric Ulcerative Colitis Activity Index (PUCAI) score greater or equal to 35 .

- No history of dysplasia or colon cancer.

- No evidence or history of untreated or inadequately treated active or latent infection with Mycobacterium Tuberculosis.

- For participants outside of the United States: 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-mercaptopurine;

- TNF inhibitors or anti integrin therapy.

- For participants in the United States: have had an inadequate response or intolerance to TNF inhibitors.

- Stable doses of the following therapies for UC:

- Oral 5 Aminosalicyclic acids (ASA) or sulfasalazine

- 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.

- evidence of prior varicella zoster virus exposure based on serological testing.

- 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).

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Diagnosis of indeterminate colitis, isolated proctitis, microscopic colitis,
infectious colitis, Crohn's disease, or clinical findings suggestive of Crohn's
disease.


- 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 4 weeks of baseline
visit.


- 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 who have previously received tofacitinib or another Janus Kinase
inhibitor.


- 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.


- Participants having received azathioprine, 6-mercaptopurine, methotrexate,
thioguanine, infliximab, adalimumab, golimumab, 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.


- Previous treatment by leukocyte apheresis including selective lymphocyte, monocyte, or
granulocyte apheresis, or plasma exchange within 6 months prior to baseline.


- 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.


- Chronic and frequent use of antimotility agents for control of diarrhea (ie,
diphenoxylate hydrochloride with atropine sulfate or loperamide).


- 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.


- 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.

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Pfizer Clinical Trials Contact Center

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Advanced Information
Descriptive Information
Brief Title  ICMJE Evaluation of Oral Tofacitinib in Children Aged 2 to 17 Years Old Suffering From Moderate to Severe Ulcerative Colitis
Official Title  ICMJE OPEN-LABEL INDUCTION AND MAINTENANCE STUDY OF ORAL CP-690,550 (TOFACITINIB) IN CHILDREN WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
Brief Summary

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 patients with prior TNFi failure or intolerance will be enrolled. Outside of the US, TNFi naïve and TNFi experienced patients 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single Group
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE Drug: tofacitinib
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.
Study Arms  ICMJE Experimental: tofacitinib
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.
Intervention: Drug: tofacitinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 9, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 7, 2028
Estimated Primary Completion Date December 16, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Evidence of a personally signed and dated informed consent document and assent document.
  • Males and females 2 to less than18 years old and weighing at least 10 kg.
  • 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.
  • 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.
  • 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.
  • Pediatric Ulcerative Colitis Activity Index (PUCAI) score greater or equal to 35 .
  • No history of dysplasia or colon cancer.
  • No evidence or history of untreated or inadequately treated active or latent infection with Mycobacterium Tuberculosis.
  • For participants outside of the United States: 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-mercaptopurine;
    • TNF inhibitors or anti integrin therapy.
  • For participants in the United States: have had an inadequate response or intolerance to TNF inhibitors.
  • Stable doses of the following therapies for UC:

    • Oral 5 Aminosalicyclic acids (ASA) or sulfasalazine
    • 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.
  • evidence of prior varicella zoster virus exposure based on serological testing.
  • 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).

Exclusion Criteria:

  • Diagnosis of indeterminate colitis, isolated proctitis, microscopic colitis, infectious colitis, Crohn's disease, or clinical findings suggestive of Crohn's disease.
  • 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 4 weeks of baseline visit.
  • 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 who have previously received tofacitinib or another Janus Kinase inhibitor.
  • 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.
  • Participants having received azathioprine, 6-mercaptopurine, methotrexate, thioguanine, infliximab, adalimumab, golimumab, 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.
  • Previous treatment by leukocyte apheresis including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
  • 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.
  • Chronic and frequent use of antimotility agents for control of diarrhea (ie, diphenoxylate hydrochloride with atropine sulfate or loperamide).
  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 2 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04624230
Other Study ID Numbers  ICMJE A3921210
2018-002378-30 ( EudraCT Number )
OVATION ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP