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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04624230




Registration number
NCT04624230
Ethics application status
Date submitted
26/10/2020
Date registered
10/11/2020
Date last updated
6/06/2024

Titles & IDs
Public title
Evaluation of Oral Tofacitinib in Children Aged 2 to 17 Years Old Suffering From 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
Secondary ID [1] 0 0
2018-002378-30
Secondary ID [2] 0 0
A3921210
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tofacitinib

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.


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Remission by central read Mayo score following 44 weeks in the maintenance phase.
Timepoint [1] 0 0
Outcome measured at the end of the 44 weeks of the maintenance phase.
Secondary outcome [1] 0 0
Response by Mayo score
Timepoint [1] 0 0
Outcome measured at induction Week 8, induction Week 16, and maintenance Week 44
Secondary outcome [2] 0 0
Remission by Mayo score
Timepoint [2] 0 0
Outcome measured at induction Week 8, induction Week 16, and maintenance Week 44
Secondary outcome [3] 0 0
Change from baseline in Mayo score.
Timepoint [3] 0 0
Outcome measured at induction Week 8, induction Week 16, and maintenance Week 44
Secondary outcome [4] 0 0
Response measured by Partial Mayo Score
Timepoint [4] 0 0
Outcome measured through study completion, an average of 3 and a half years
Secondary outcome [5] 0 0
Change from baseline in Partial Mayo score
Timepoint [5] 0 0
Outcome measured through study completion, an average of 3 and a half years
Secondary outcome [6] 0 0
Response by PUCAI score
Timepoint [6] 0 0
Outcome measured through study completion, an average of 3 and a half years
Secondary outcome [7] 0 0
Change from baseline in PUCAI score
Timepoint [7] 0 0
Outcome measured through study completion, an average of 3 and a half years
Secondary outcome [8] 0 0
Percentage of Participants Achieving Endoscopic Improvement at Week 8, 16, and 44
Timepoint [8] 0 0
Outcome measured at induction Week 8, induction Week 16, and maintenance Week 44
Secondary outcome [9] 0 0
Time to flare
Timepoint [9] 0 0
Outcome measured from 2 to 4 months in the study, through study completion, an average of 3 and a half years
Secondary outcome [10] 0 0
Change from baseline in fecal calprotectin levels
Timepoint [10] 0 0
Outcome measured through study completion, an average of 3 and a half years
Secondary outcome [11] 0 0
Change from baseline in serum high sensitivity C-Reactive Protein (hsCRP) levels
Timepoint [11] 0 0
Outcome measured through study completion, an average of 3 and a half years
Secondary outcome [12] 0 0
Corticosteroid free remission by Partial Mayo Score
Timepoint [12] 0 0
Outcome measured through study completion, an average of 3 and a half years
Secondary outcome [13] 0 0
Average plasma concentration of tofacitinib (Cavg)
Timepoint [13] 0 0
Outcome measured at baseline, induction Week 8, induction Week 16, maintenance Week 16, maintenance Week 44
Secondary outcome [14] 0 0
Evaluation of taste acceptability of tofacitinib oral solution, and acceptability of film coated tablet by choosing one of 5 choices
Timepoint [14] 0 0
Outcome measured at induction week 2
Secondary outcome [15] 0 0
Peak (maximum) plasma concentration of tofacitinib (Cmax)
Timepoint [15] 0 0
Outcome measured at baseline, induction Week 8, induction Week 16, maintenance Week 16, maintenance Week 44
Secondary outcome [16] 0 0
Percentage of Participants Achieving Endoscopic Remission at Week 8, 16, and 44
Timepoint [16] 0 0
Outcome measured at induction Week 8, induction Week 16, and maintenance Week 44
Secondary outcome [17] 0 0
Remission by PUCAI score
Timepoint [17] 0 0
Outcome measured through study completion, an average of 3 and a half years

Eligibility
Key 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 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:

- Oral or intravenous (IV) corticosteroids;

- Azathioprine or 6-mercaptopurine;

- TNF inhibitors or anti integrin therapy.

- For participants in the United States and the European Union: 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.

- 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).
Minimum age
2 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 2 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, 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.

- 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.

- History of allergies, intolerance or hypersensitivity to lactose or tofacitinib, or
any other excipients of the investigational medicinal products, including placebos.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/12/2026
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Women's and Children's Hospital, Women's and Children's Health Network Inc. - North Adelaide
Recruitment hospital [2] 0 0
The Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Belgium
State/province [15] 0 0
Vlaams Brabant
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussels
Country [17] 0 0
Belgium
State/province [17] 0 0
Brussel
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Nova Scotia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Finland
State/province [23] 0 0
Tampere
Country [24] 0 0
France
State/province [24] 0 0
BRON Cedex
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
Germany
State/province [26] 0 0
Bavaria
Country [27] 0 0
Hungary
State/province [27] 0 0
Hajdú-bihar
Country [28] 0 0
Hungary
State/province [28] 0 0
Debrecen
Country [29] 0 0
Hungary
State/province [29] 0 0
Miskolc
Country [30] 0 0
Hungary
State/province [30] 0 0
Szeged
Country [31] 0 0
Israel
State/province [31] 0 0
Be'er Ya'akov
Country [32] 0 0
Israel
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Haifa
Country [33] 0 0
Israel
State/province [33] 0 0
Jerusalem
Country [34] 0 0
Israel
State/province [34] 0 0
Petah Tikva
Country [35] 0 0
Israel
State/province [35] 0 0
Tel Aviv
Country [36] 0 0
Italy
State/province [36] 0 0
BG
Country [37] 0 0
Italy
State/province [37] 0 0
Naples
Country [38] 0 0
Italy
State/province [38] 0 0
RM
Country [39] 0 0
Italy
State/province [39] 0 0
Bologna
Country [40] 0 0
Japan
State/province [40] 0 0
Aichi
Country [41] 0 0
Japan
State/province [41] 0 0
Fukuoka
Country [42] 0 0
Japan
State/province [42] 0 0
Gunma
Country [43] 0 0
Japan
State/province [43] 0 0
Miyagi
Country [44] 0 0
Japan
State/province [44] 0 0
Osaka
Country [45] 0 0
Japan
State/province [45] 0 0
Saitama
Country [46] 0 0
Japan
State/province [46] 0 0
Tochigi
Country [47] 0 0
Japan
State/province [47] 0 0
Tokyo
Country [48] 0 0
Netherlands
State/province [48] 0 0
Amsterdam
Country [49] 0 0
Netherlands
State/province [49] 0 0
Rotterdam
Country [50] 0 0
Poland
State/province [50] 0 0
Bydgoszcz
Country [51] 0 0
Poland
State/province [51] 0 0
Lodz
Country [52] 0 0
Poland
State/province [52] 0 0
Rzeszow
Country [53] 0 0
Poland
State/province [53] 0 0
Warsaw
Country [54] 0 0
Poland
State/province [54] 0 0
Warszawa
Country [55] 0 0
Poland
State/province [55] 0 0
Wroclaw
Country [56] 0 0
Slovakia
State/province [56] 0 0
Bratislava
Country [57] 0 0
Spain
State/province [57] 0 0
Barcelona
Country [58] 0 0
Spain
State/province [58] 0 0
Málaga
Country [59] 0 0
Spain
State/province [59] 0 0
Madrid
Country [60] 0 0
Sweden
State/province [60] 0 0
Göteborg
Country [61] 0 0
Sweden
State/province [61] 0 0
Stockholm
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Greater London
Country [63] 0 0
United Kingdom
State/province [63] 0 0
WEST Midlands
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Edinburgh
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Glasgow
Country [66] 0 0
United Kingdom
State/province [66] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04624230
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04624230