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TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600, AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE

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ClinicalTrials.gov Identifier: NCT04413617
Recruitment Status : Completed
First Posted : June 4, 2020
Last Update Posted : March 4, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
Dual objectives of increased efficacy compared to currently available SoC RA drugs and maintaining a favourable benefit - risk relationship.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: PF-06650833 Drug: PF-06651600 Drug: Tofacitinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 460 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 24-WEEK RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP, ACTIVE COMPARATOR, MULTICENTER STUDY TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600 (RITLECITINIB) AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH MODERATELY-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
Actual Study Start Date : July 29, 2020
Actual Primary Completion Date : February 7, 2022
Actual Study Completion Date : February 7, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-06650833 + tofacitinib Drug: PF-06650833
400 mg

Drug: Tofacitinib
11 mg

Experimental: PF-06650833 + PF-06651600 Drug: PF-06650833
400 mg

Drug: PF-06651600
100 mg

Experimental: PF-06650833 Drug: PF-06650833
400 mg

Experimental: PF-06651600 Drug: PF-06651600
100 mg

Experimental: Tofacitinib Drug: Tofacitinib
11 mg




Primary Outcome Measures :
  1. Change from baseline in Disease Activity Score (DAS)28-C Reactive protein (CRP) [ Time Frame: Week 12 ]

Secondary Outcome Measures :
  1. DAS28-CRP remission (<2.6) [ Time Frame: Week 24 ]
  2. Change from baseline in Disease Activity Score (DAS)28-C Reactive protein (CRP) [ Time Frame: Week 24 ]
  3. American College of Rheumatology (ACR)20, ACR 50, ACR 70, and ACR 90 responder rates [ Time Frame: Weeks 12 and 24 ]
  4. Change from baseline in the Tender/Painful and Swollen Joint Count [ Time Frame: Weeks 12 and 24 ]
  5. Change from baseline in the Physician's Global Assessment (PhGA) of Arthritis [ Time Frame: Weeks 12 and 24 ]
  6. Incidence and severity of adverse events, serious adverse events, and withdrawals due to adverse events. [ Time Frame: Baseline through Week 28 ]
  7. Incidence of abnormality in clinical chemistry parameters [ Time Frame: Baseline through Week 28 ]
  8. Incidence of abnormality in hematological parameters [ Time Frame: Baseline through Week 28 ]
  9. Change from baseline in blood pressure measurement [ Time Frame: Baseline through Week 28 ]
  10. Change from baseline in pulse rate measurement [ Time Frame: Baseline through Week 28 ]
  11. Change from baseline in temperature measurement [ Time Frame: Baseline through Week 28 ]
  12. Incidences of targeted medical adverse events [ Time Frame: Baseline through Week 28 ]


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female participants between the ages of 18 and 70 years.
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  • 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.
  • The participant has active disease at both Screening and Randomization, as defined by both: ≥6 joints tender or painful on motion, AND ≥6 joints swollen; and fulfills 1 of the following 2 criteria: High sensitivity C reactive protein (hsCRP) >7 mg/L at Screening (Visit 1) as performed by the central laboratory OR Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm h.

Exclusion Criteria:

  • 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 IP 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 with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
  • Participants with any active or latent infections.
  • Participants with positive hepatitis B surface antigen (HBsAg).
  • Participants with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA).
  • Any history of either untreated or inadequately treated latent or active tuberculosis (TB) infection, current treatment for active or latent TB infection or evidence of currently active TB,
  • History of a major organ transplant (eg, heart, lung, kidney and liver) or hematopoietic stem cell/marrow transplant.
  • History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations.
  • Known history of diverticulitis or symptomatic diverticulosis, perineal abscess or fistulae.
  • Participants with malignancy or history of malignancy (including lymphoma, leukemia, or lymphoproliferative disease).
  • Pre-existing chronic autoimmune disease (eg, inflammatory bowel disease, systemic lupus erythematosus, moderate-severe atopic dermatitis, dermatomyositis) other than RA. Secondary Sjogren's Syndrome (due to RA) may be included.
  • Participants with fibromyalgia will be excluded.
  • Previous treatment with total lymphoid irradiation.
  • Participants with an oral, tympanic, or temporal temperature of 38°C (100.4°F) or higher at baseline.
  • Participants may not receive any live/attenuated vaccine from 30 days prior to randomization during the course of the study, or for 30 days after the last dose of study medication. Participants who have current routine household contact with children who have received varicella or oral polio vaccine within 2 months of first study dose are also excluded.
  • History of any lymphoproliferative disorder.
  • Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease.
  • History of any prior deep vein thrombosis (DVT) or pulmonary embolism [PE].
  • Recent (within 6 months of screening) myocardial infarction, coronary revascularization, or percutaneous angioplasty with or without placement of a coronary artery stent; acute coronary syndrome; chronic uncompensated heart failure or New York Heart Association Functional Class III or IV; left ventricular assist devices; implanted defibrillators.
  • Current severe chronic renal insufficiency or renal failure as defined by persistent (on repeated measurements) eGFR <60 mL/min per 1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation.
  • Any known coagulopathy or hypercoagulant syndrome.
  • Presence of any of the following laboratory abnormalities at screening or within the 3 months prior to first study dose:

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥1.5 x the upper limit of normal (ULN); Participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN and other liver function assessments are normal; Absolute neutrophil count of <1.5 x 109/L (<1500/mm3). Participants with cyclic (benign ethnic) neutropenia will be excluded; Absolute lymphocyte count of <0.5 x 109/L (<500/mm3); Absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3); Hemoglobin <9.0 g/dL (90 g/L); Platelet count ≤100 x 109/L (100,000 cells/mm3) or ≥1000 x 109/L (1,000,000 cells/mm3); Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at screening visit or within the 3 months prior to first study dose. [Screening laboratory tests with abnormal results may be repeated once to confirm abnormal results. If results return to normal protocol acceptable limits within the 4-week screening period, the participant may enter the study].

- Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity scale, except for the following that are allowed: Grade 3 prothrombin time (PT) secondary to warfarin treatment; Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.

  • Participants previously treated with a biologic DMARD (except for up to 25% of participants who may have been treated with 1, and only 1 prior TNF inhibitor) or any other recent DMARD treatment (eg, a JAK inhibitor), or participants currently treated with any other prohibited medications will be excluded.
  • Prior use of tofacitinib or other JAK inhibitor in the context of a clinical trial is excluded. Concomitant use of tofacitinib (other than as prescribed by the randomization scheme) or other JAK inhibitor is prohibited.
  • Participants who have previously been treated with other, non-TNFa inhibiting biologic DMARDs [including, abatacept (Orencia®), tocilizumab (Actemra®), Sarilumab (Kevzara®), anakinra (Kineret®), rituximab (Rituxan®) or other selective B lymphocyte depleting agents, or other lymphocyte depleting agents/therapies (such as alemtuzab [CamPath®], natalizumab (Tysabri®), alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation) are excluded from participation in the study.
  • Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of IP used in this study (whichever is longer).
  • Any 12-lead electrocardiogram (ECG) performed prior to randomization that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

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): NCT04413617


Locations
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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: NCT04413617    
Other Study ID Numbers: B7921023
2019-002676-14 ( EudraCT Number )
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: March 4, 2022
Last Verified: March 2022
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Pfizer:
Rheumatoid Arthritis
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
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action