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Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT02831855
Recruitment Status : Completed
First Posted : July 13, 2016
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This study is designed to evaluate the efficacy and safety of tofacitinib modified release formulation (11mg QD) versus tofacitinib modified release formulation plus continued methotrexate treatment in subjects with moderate to severe rheumatoid arthritis who are insufficiently responding to their stable dose of methotrexate treatment.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: CP-690,550 Drug: Methotrexate Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 695 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : September 1, 2016
Actual Primary Completion Date : November 19, 2018
Actual Study Completion Date : December 17, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CP-690,550 and methotrexate
Open-label tofacitinib tablet and blinded methotrexate capsule
Drug: 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.

Other Name: tofacitinib

Drug: 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.


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




Primary Outcome Measures :
  1. Change in DAS28-4 (ESR) score from randomization (at week 24) to the end of double-blind MTX withdrawal phase (at week 48) [ Time Frame: week 48 ]

Secondary Outcome Measures :
  1. Change in the DAS28-4(ESR) from week 24 to week 36 [ Time Frame: week 36 ]
  2. Change in the DAS28-4 (CRP) from week 24 to week 48 [ Time Frame: week 48 ]
  3. Change in the CDAI from week 24 to week 48 [ Time Frame: week 48 ]
  4. Change in SDAI from week 24 to week 48 [ Time Frame: week 48 ]
  5. change in the DAS28-4 (CRP) from week 24 to week 36 [ Time Frame: week 36 ]
  6. Change in the CDAI from week 24 to week 36 [ Time Frame: week 36 ]
  7. Change in the SDAI from week 24 to week 36 [ Time Frame: week 36 ]
  8. LDA as assessed by DAS28-4(ESR) <=3.2 at week 48 [ Time Frame: week 48 ]
  9. LDA as assessed by DAS28-4(CRP) <=3.2 at week 48 [ Time Frame: week 48 ]
  10. LDA as assessed by CDAI<=10 at week 48 [ Time Frame: week 48 ]
  11. LDA as assessed by SDAI<=11 at week 48 [ Time Frame: week 48 ]
  12. LDA as assessed by DAS28-4(ESR) <=3.2 at week 36 [ Time Frame: week 36 ]
  13. LDA as assessed by DAS28-4(CRP) <=3.2 at week 36 [ Time Frame: week 36 ]
  14. LDA as assessed by CDAI<=10 at week 36 [ Time Frame: week 36 ]
  15. LDA as assessed by SDAI<=11 at week 36 [ Time Frame: week 36 ]
  16. Remission as assessed by ACR-EULAR Boolean remission criteria at week 48 [ Time Frame: week 48 ]
  17. Remission as assessed by DAS28-4 (ESR)<2.6 at week 48 [ Time Frame: week 48 ]
  18. Remission as assessed by DAS28-4 (CRP)<2.6 at week 48 [ Time Frame: week 48 ]
  19. Remission as assessed by CDAI≤2.8 at week 48 [ Time Frame: week 48 ]
  20. Remission as assessed by SDAI≤3.3 at week 48 [ Time Frame: week 48 ]
  21. Remission as assessed by ACR-EULAR Boolean remission criteria at week 36 [ Time Frame: week 36 ]
  22. Remission as assessed by DAS28-4 (ESR)<2.6 at week 36 [ Time Frame: week 36 ]
  23. Remission as assessed by DAS28-4 (CRP)<2.6 at week 36 [ Time Frame: week 36 ]
  24. Remission as assessed by CDAI≤2.8 at week 36 [ Time Frame: week 36 ]
  25. Remission as assessed by SDAI≤3.3 at week 36 [ Time Frame: week 36 ]
  26. ACR20 response at week 48 [ Time Frame: week 48 ]
  27. ACR50 response at week 48 [ Time Frame: week 48 ]
  28. ACR70 response at week 48 [ Time Frame: week 48 ]
  29. ACR20 response at week 36 [ Time Frame: week 36 ]
  30. ACR50 response at week 36 [ Time Frame: week 36 ]
  31. ACR70 response at week 36 [ Time Frame: week 36 ]
  32. Change in the HAQ-DI from week 24 to week 48 [ Time Frame: week 48 ]
  33. Change in the SF-36 (8 domain scores and 2 component scores) from week 24 to week 48 [ Time Frame: week 48 ]
  34. Change in the WPAI score from week 24 to week 48 [ Time Frame: week 48 ]
  35. Change in the EuroQol EQ-5D score from week 24 to week 48 [ Time Frame: week 48 ]
  36. Change in the FACIT-Fatigue scale score from week 24 to week 48 [ Time Frame: week 48 ]
  37. Change in the HAQ-DI from week 24 to week 36 [ Time Frame: week 36 ]
  38. Change in the SF-36 (8 domain scores and 2 component scores) from week 24 to week 36 [ Time Frame: week 36 ]
  39. Change in the WPAI score from week 24 to week 36 [ Time Frame: week 36 ]
  40. Change in the EuroQol EQ-5D score from week 24 to week 36 [ Time Frame: week 36 ]
  41. Change in the FACIT-Fatigue scale score from week 24 to week 36 [ Time Frame: week 36 ]
  42. HAQ-DI response (ie, decrease of at least 0.22) at week 48 [ Time Frame: week 48 ]
  43. HAQ-DI response (ie, decrease of at least 0.22) at week 36 [ Time Frame: week 36 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02831855


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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Publications:
Ware JE KM, Dewey JE. . How to score Version 2 of the SF 36 Health Survey (Standard & Acute forms). In: How to score Version 2 of the SF 36 Health Survey (Standard & Acute forms). Lincoln, Rhode Island: QualityMetric, Incorporated. 2000.

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02831855     History of Changes
Other Study ID Numbers: A3921192
2016-001825-15 ( EudraCT Number )
First Posted: July 13, 2016    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
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/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Keywords provided by Pfizer:
Rheumatoid Arthritis
Tofacitinib
CP-690,550
Xeljanz
methotrexate withdrawal
withdrawal study

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Tofacitinib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors