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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02831855




Registration number
NCT02831855
Ethics application status
Date submitted
11/07/2016
Date registered
13/07/2016

Titles & IDs
Public title
Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis
Scientific title
A PHASE 3B/4 RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED STUDY OF METHOTREXATE (MTX) WITHDRAWAL IN SUBJECTS WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH TOFACITINIB 11MG MODIFIED RELEASE (MR) FORMULATION
Secondary ID [1] 0 0
2016-001825-15
Secondary ID [2] 0 0
A3921192
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CP-690,550
Treatment: Drugs - Methotrexate
Treatment: Drugs - Placebo

Experimental: CP-690,550 and methotrexate - Open-label tofacitinib tablet and blinded methotrexate capsule

Placebo comparator: CP-690,550 and placebo - open-label tofacitinib tablet and blinded matching placebo for methotrexate capsule


Treatment: Drugs: CP-690,550
During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose.

During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.

Treatment: Drugs: Methotrexate
During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose.

During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.

Treatment: Drugs: Placebo
During the double-blind phase, subjects who are randomized to the comparison arm will receive 11mg QD tofacitinib and the placebo capsules matching for methotrexate.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48
Timepoint [1] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48
Secondary outcome [1] 0 0
Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36
Timepoint [1] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36
Secondary outcome [2] 0 0
Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48
Timepoint [2] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [3] 0 0
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48
Timepoint [3] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [4] 0 0
Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48
Timepoint [4] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [5] 0 0
Double Blind Phase: Percentage of Participants With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48
Timepoint [5] 0 0
Weeks 36 and 48
Secondary outcome [6] 0 0
Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48
Timepoint [6] 0 0
Weeks 36 and 48
Secondary outcome [7] 0 0
Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48
Timepoint [7] 0 0
Weeks 36 and 48
Secondary outcome [8] 0 0
Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48
Timepoint [8] 0 0
Weeks 36 and 48
Secondary outcome [9] 0 0
Double Blind Phase: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48
Timepoint [9] 0 0
Weeks 36 and 48
Secondary outcome [10] 0 0
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48
Timepoint [10] 0 0
Weeks 36 and 48
Secondary outcome [11] 0 0
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48
Timepoint [11] 0 0
Weeks 36 and 48
Secondary outcome [12] 0 0
Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48
Timepoint [12] 0 0
Weeks 36 and 48
Secondary outcome [13] 0 0
Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48
Timepoint [13] 0 0
Weeks 36 and 48
Secondary outcome [14] 0 0
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48
Timepoint [14] 0 0
Baseline (Day 1), Weeks 36 and 48
Secondary outcome [15] 0 0
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48
Timepoint [15] 0 0
Baseline (Day 1), Weeks 36 and 48
Secondary outcome [16] 0 0
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48
Timepoint [16] 0 0
Baseline (Day 1), Weeks 36 and 48
Secondary outcome [17] 0 0
Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48
Timepoint [17] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [18] 0 0
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48
Timepoint [18] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [19] 0 0
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48
Timepoint [19] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [20] 0 0
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48
Timepoint [20] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
Secondary outcome [21] 0 0
Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48
Timepoint [21] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [22] 0 0
Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48
Timepoint [22] 0 0
Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Secondary outcome [23] 0 0
Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48
Timepoint [23] 0 0
Baseline (Day 1), Weeks 36 and 48

Eligibility
Key inclusion criteria
Key Inclusion Criteria

- Must be 18 years of age or older.

Have a score of 6 or greater on the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis at and/or prior to Screening Visit.

* Have =4 tender/painful joints on motion and =4 swollen joints (28 joint counts) at both Screening Visit and Baseline Visit (Visit 1).
* Have moderate to severe disease activity as defined by CDAI>10 and DAS28-4(ESR) =3.2 at Baseline Visit.
* Have taken an oral MTX treatment regimen (15-25mg/week) continuously for at least 4 months prior to the screening visit and has taken a stable weekly dose of oral MTX with supplemental folic acid or folinic acid for at least 4 weeks prior to the baseline visit (conversion from parenteral MTX to oral MTX will require stabilization of the treatment regimen for at least 1 month).
* Subjects must screen negative for active tuberculosis or inadequately treated tuberculosis infection (active or latent).

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product.
* Subjects with infection or infection history; subjects with any current malignancy or a history of malignancy (except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ); subjects with history of, or current evidence for, severe gastrointestinal narrowing (pathologic or iatrogenic); and subjects with history of documented diverticulitis.
* Subjects with a history of insufficient response to =2 biologics, regardless of the class.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/12/2018
Sample size
Target
Accrual to date
Final
694
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Genesis Research Services Pty Ltd - Broadmeadow
Recruitment hospital [2] 0 0
Optimus Clinical Research Pty Ltd - Kogarah
Recruitment hospital [3] 0 0
Rheumatology Research Unit - Maroochydore
Recruitment hospital [4] 0 0
Emeritus Research - Melbourne
Recruitment postcode(s) [1] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4558 - Maroochydore
Recruitment postcode(s) [4] 0 0
3124 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
North Dakota
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
South Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
Belgium
State/province [23] 0 0
Genk
Country [24] 0 0
Belgium
State/province [24] 0 0
Roeselare
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Pleven
Country [26] 0 0
Bulgaria
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Plovdiv
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Bulgaria
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Sofia
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Czechia
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Czech Republic
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Czechia
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Brno
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Czechia
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Ostrava
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha 2
Country [32] 0 0
Czechia
State/province [32] 0 0
Uherske Hradiste
Country [33] 0 0
Czechia
State/province [33] 0 0
Zlin
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Hungary
State/province [35] 0 0
Balatonfured
Country [36] 0 0
Hungary
State/province [36] 0 0
Budapest
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Hungary
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Miskolc
Country [38] 0 0
Korea, Republic of
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Seoul
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Mexico
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Ciudad DE Mexico
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Mexico
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Guanajuato
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Philippines
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Batangas
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Philippines
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Metro Manila
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Poland
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Bialystok
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Poland
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Bytom
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Poland
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Krakow
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Poland
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Nadarzyn
Country [47] 0 0
Poland
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Warszawa
Country [48] 0 0
Russian Federation
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Moscow
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Russian Federation
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Orenburg
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saint-Petersburg
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Russian Federation
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Samara
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Russian Federation
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Smolensk
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Yaroslavl
Country [55] 0 0
Slovakia
State/province [55] 0 0
Dunajska Streda
Country [56] 0 0
Slovakia
State/province [56] 0 0
Martin
Country [57] 0 0
Slovakia
State/province [57] 0 0
Partizanske
Country [58] 0 0
Slovakia
State/province [58] 0 0
Poprad
Country [59] 0 0
Slovakia
State/province [59] 0 0
Rimavska Sobota
Country [60] 0 0
South Africa
State/province [60] 0 0
Kwazulu Natal
Country [61] 0 0
Spain
State/province [61] 0 0
A Coruna
Country [62] 0 0
Spain
State/province [62] 0 0
Vizcaya
Country [63] 0 0
Spain
State/province [63] 0 0
Sevilla
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Cheshire
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Hampshire
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Merseyside
Country [67] 0 0
United Kingdom
State/province [67] 0 0
WEST Midlands
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02831855