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Safety and Efficacy of Pf-06650833 In Subjects With Rheumatoid Arthritis, With An Inadequate Response To Methotrexate

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ClinicalTrials.gov Identifier: NCT02996500
Recruitment Status : Completed
First Posted : December 19, 2016
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a Phase 2, multicenter, randomized, double blind, double dummy, placebo and active-controlled, parallel group study to assess the efficacy and safety of PF 06650833 at Week 12 in subjects with moderate-severe, active, RA who have had an inadequate response to MTX. PF-06650833 or matching placebo tablets will be administered orally QD under fasting conditions, and tofacitinib or matching tofacitinib placebo tablets will be administered orally BID for 12 weeks in a blinded fashion.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: PF-06650833 Drug: Placebo Drug: Tofacitinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 269 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12 Week Randomized, Double-blind, Double Dummy, Parallel Group, Active And Placebo-controlled, Multicenter Study To Assess The Efficacy And Safety Profile Of Pf-06650833 In Subjects With Active Rheumatoid Arthritis With An Inadequate Response To Methotrexate
Actual Study Start Date : November 2016
Actual Primary Completion Date : August 2018
Actual Study Completion Date : August 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1: 20 mg QD
PF-06650833 , 20 mg QD
Drug: PF-06650833
Investigational

Experimental: Arm 2: 60 mg QD
PF-06650833, 60 mg QD
Drug: PF-06650833
Investigational

Experimental: Arm 3: 200 mg QD
Pf-06650833, 200 mg QD
Drug: PF-06650833
Investigational

Experimental: Arm 4: 400 mg QD
PF-06650833, 400 mg QD
Drug: PF-06650833
Investigational

Placebo Comparator: Placebo
Placebo, 0 mg BID
Drug: Placebo
Placebo

Active Comparator: Arm 5: Tofacitinib
Tofacitinib 5 mg BID
Drug: Tofacitinib
Investigational
Other Name: Xeljanz




Primary Outcome Measures :
  1. Change from baseline in the Simplified Disease Activity Index (SDAI) at Week 12 [ Time Frame: Baseline and 12 weeks ]

Secondary Outcome Measures :
  1. Change from baseline in SDAI [ Time Frame: Baseline, 4 and 8 weeks ]
  2. SDAI low disease activity score (LDAS) [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  3. DAS28 LDAS [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  4. Change from baseline DAS28-3 [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  5. ACR 20 responder rates [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  6. Change from baseline in the Tender/Painful and Swollen Joint Counts [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  7. Change from baseline in high sensitivity C-reactive protein (hsCRP) [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  8. Change from baseline in the Physician's Global Assessment of Arthritis (PhGA) [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  9. Change from baseline in the Patient's Assessment of Arthritis Pain (PAAP) VAS [ Time Frame: Baseline, 4, 8 and 12 ]
  10. Change from baseline in Patient Global Assessment of Arthritis (PtGA) VAS [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  11. Change from baseline in the HAQ-DI [ Time Frame: Baseline, 4, 8 and 12 weeks ]
  12. Change from baseline in the SF 36v.2 (acute) 8 Domain scores [ Time Frame: Baseline and 12 weeks ]
  13. Change from baseline in the EQ-5D 3L score [ Time Frame: Baseline and 12 weeks ]
  14. Change from baseline in the FACIT-F total score [ Time Frame: Baseline and 12 weeks ]
  15. Safety and tolerability of PF 06650833: vital signs (blood pressure, pulse, and temperature), laboratory tests, Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline, 1, 4, 6 , 8, 10, 12, 14 and 16 weeks ]
  16. Urinalysis including urine microscopy. [ Time Frame: Baseline, 1, 4, 6, 8, 10, 12, 14 and 16 weeks ]
  17. 12 lead ECG [ Time Frame: Baseline, 1, 12 and 16 weeks ]
  18. DAS-28 remission rate [ Time Frame: 4, 8 and 12 weeks ]
  19. SDAI remission rate [ Time Frame: 4, 8, and 12 weeks ]
  20. Change from baseline DAS28 3 (CRP) [ Time Frame: Baseline, 4,8 and 12 ]
  21. Change from baseline DAS28 -4 (ESR) [ Time Frame: Baseline, 4, 8 and 12 ]
  22. Change from baseline DAS28 4 (CRP) [ Time Frame: Baseline, 4, 8 and 12 ]
  23. ACR 50responder rates [ Time Frame: Baseline, 4, 8 and 12 ]
  24. ACR 70 responder rates [ Time Frame: Baseline, 4, 8 and 12 ]
  25. Change from baseline in Physical Component Score (PCS) [ Time Frame: Baseline and 12 weeks ]
  26. Change from baseline in Mental component score (MCS) [ Time Frame: Baseline and 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female (including WOCBP) subjects between the ages of 18 and 75 years, inclusive.
  2. Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.
  3. The subject has active disease at both Screening and Baseline, as defined by both:

    • 6 joints tender or painful on motion, AND
    • 6 joints swollen; and fulfills 1 of the following 2 criteria at Screening:
    • High sensitivity C reactive protein (hsCRP) >7 mg/L at screening
    • Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr;
  4. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
  5. Subjects must be ACPA positive between screening and randomization.
  6. Subjects must have been taking oral MTX for at least 3 months at an adequate dose to determine that the subject had an inadequate response to MTX
  7. Up to 50 % of subjects may have received one (and only one) approved TNF-inhibiting biologic agent administered that was inadequately effective and/or not tolerated. The anti-TNF biologic could also have been discontinued due to lack of continued access.

Exclusion Criteria:

  1. Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
  2. Subjects with any of the following infections or infections history:

    1. Any infection requiring treatment within 2 weeks prior to screening (Visit 1).
    2. Any infection requiring hospitalization, parenteral antimicrobial therapy within 60 days, or as otherwise judged to be an opportunistic infection or clinically significant by the investigator, within the past 6 months.
    3. Infected joint prosthesis at any time with the prosthesis still in situ.
    4. Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
    5. Subjects will be screened for HIV. Subjects who test positive for HIV will be excluded from the study.
    6. Subjects will be screened for hepatitis B virus infection and will be excluded if positive for hepatitis B surface antigen (HBsAg). Subjects with HBsAg negative testing but who test positive for hepatitis B core antibody (HBcAb) must have further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative, the subject will be excluded from the study.
    7. Subjects with clinically significant active hepatic disease or hepatic impairment by laboratory assessment.
    8. Subjects will be screened for hepatitis C virus (HCV Ab). Subjects with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only subjects with negative HCV Ab or HCV RNA will be allowed to enroll in the study.
  3. Evidence of active or latent, untreated or inadequately treated infection with Mycobacterium tuberculosis (TB)
  4. Pre-existing chronic autoimmune disease.

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): NCT02996500


  Show 103 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02996500     History of Changes
Other Study ID Numbers: B7921005
2016-002337-30 ( EudraCT Number )
IRAK 4 ( Other Identifier: Alias Study Number )
First Posted: December 19, 2016    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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