A STUDY TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF 06651600, AND TOFACITINIB. ALONE AND IN COMBINATION IN ACTIVE RHEUMATOID ARTHRITIS
- Conditions
- Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by joint inflammationMedDRA version: 21.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-002676-14-HU
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 450
1. Male or female participants between the ages of 18 and 70 years, inclusive, at time of randomization (Visit 2).
2. Participants who are willing and able to comply with all scheduled visits, treatment plan (including washout of MTX at randomization), laboratory tests, lifestyle considerations, and other study procedures.
3. 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 duration of time since diagnosis of RA should minimally be sufficient to meet the definition of MTX inadequate response (MTX IR)
4. The participant has active disease at both Screening and Randomization, as defined by both:
• equal to or greater than 6 joints tender or painful on motion, AND
• equal to or greater than 6 joints swollen;
and fulfills 1 of the following 2 criteria at or before randomization:
• 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.
5. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA
6. Participants must be seropositive at the time of randomization (ACPA or RF positive).
7. Participants must have been taking oral MTX (or equivalent parenteral MTX) at an adequate dose and for a sufficient duration (generally at least 3 months but may be as short as at least 8 weeks if consistent with local standard of care treatment guidelines) prior to Screening (Visit 1) to determine that the participant had an inadequate response to MTX, defined, for the purpose of this study, by the investigator’s and participant’s opinions that the participant did not experience adequate benefit from MTX plus the presence of sufficient residual disease activity to meet the entry criteria.
8. Participants receiving non prohibited concomitant medications for any reason must be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half lives (whichever is longer) prior to first study dose.
9. Body weight must be >40 kg.
10. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
1. Other acute or chronic medical or psychiatric condition including recent or active suicidal ideation or behavior or laboratory abnormality
2. Participants with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
3. Participants with any of the following infections
a. Any infection requiring treatment within 2 weeks prior to screening
b. Any infection requiring hospitalization, parenteral antimicrobial therapy within 60 days, within the past 6 months.
c. Infected joint prosthesis at any time with the prosthesis still in situ.
d. Recurrent herpes zoster; or severe or disseminated herpes simplex.
e. Participants who test positive for HIV will be excluded
4. Participants with positive hepatitis B surface antigen (HBsAg) will be excluded. Participants who are HBsAg negative but HBcAb positive will be reflex tested for hepatitis B virus deoxyribonucleic acid (HBV DNA) and, if HBV DNA is negative, will be allowed to enroll in the study
5. Participants will be screened for hepatitis C virus (HCV Ab). Participants with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only participants with negative HCV Ab or HCV RNA, and normal liver function will be allowed to enroll
6. 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 by chest x ray, CT or MRI, residing with or frequent close contact with individual(s) with active TB.
7. History of a major organ transplant (eg, heart, lung, kidney and liver) or hematopoietic stem cell/marrow transplant.
8. History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations.
9. Known history of diverticulitis or symptomatic diverticulosis, perineal abscess or fistulae.
10. Participants with malignancy or history of malignancy (including lymphoma, leukemia, or lymphoproliferative disease), with the exception of participants with adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
11. 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.
12. Participants with fibromyalgia
13. Major surgery within 4 weeks of screening or planned surgery scheduled to occur during the study.
14. Previous treatment with total lymphoid irradiation.
15. Participants with any condition possibly affecting oral drug absorption (eg, bariatric/obesity surgery, gastrectomy, or clinically significant diabetic gastroenteropathy).
16. Participants with an oral, tympanic, or temporal temperature of 38°C (100.4°F) or higher at baseline.
17. 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 excluded who have current routine household contact with children who have received varicella or oral polio vaccine within 2 months of first study dose.
18. History of any lymphoproliferative disorder
19. Have hearing loss with progression over the previous 5 years
20. Deep vein thrombosis (DVT) or pulmonary embolism [PE].
21. Recent myocardial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method