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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02996500
• Date of registration: 13/10/2016
• Prospective Registration: Yes
• Primary sponsor: Pfizer
• Public title: Safety and Efficacy of Pf-06650833 In Subjects With Rheumatoid Arthritis, With An Inadequate Response To Methotrexate
• Scientific 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
• Date of first enrolment: November 10, 2016
• Target sample size: 269
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02996500
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Australia, Bosnia and Herzegovina, Bulgaria, Croatia, Czechia, Georgia, Germany, Hungary, Korea, Republic of, Mexico, Poland, Romania, Russian Federation, Serbia, Slovakia, Spain, Taiwan, Ukraine, United States

Contacts

• Name: Pfizer CT.gov Call Center
• Affiliation: Pfizer

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: PF-06650833

Drug: Tofacitinib

Drug: Placebo

Primary Outcome(s)

Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12 [Time Frame: Baseline and Week 12]

Secondary Outcome(s)

Change From Baseline in DAS28-4 (CRP) at 4, 8 and 12 Weeks [Time Frame: Baseline, Weeks 4, 8 and 12]

Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12 [Time Frame: Baseline and Week 12]

Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria [Time Frame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

Percentage of Participants With DAS28-3 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Weeks 4, 8, and 12 [Time Frame: Baseline, Weeks 4, 8 and 12]

Change From Baseline in the Physician's Global Assessment of Arthritis (PhGA) at 4, 8, and 12 Weeks [Time Frame: Baseline, Weeks 4, 8 and 12]

Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) [Time Frame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

Number of Participants With Urinalysis Data Meeting Pre-specified Criteria [Time Frame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

Change From Baseline in SDAI at Weeks 4 and 8 [Time Frame: Baseline, Weeks 4 and 8]

Percentage of Participants With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at 4, 8, and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Change From Baseline in DAS28-3 (ESR) at 4, 8 and 12 Weeks [Time Frame: Baseline, Weeks 4, 8 and 12]

Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at 4, 8 and 12 Weeks [Time Frame: Baseline, Weeks 4, 8 and 12]

Change From Baseline in the Tender/Painful and Swollen Joint Counts at 4, 8 and 12 Weeks [Time Frame: Baseline, Weeks 4, 8 and 12]

Percentage of Participants With DAS28-3 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Percentage of Participants With DAS28-3 (ESR) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Percentage of Participants With Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Change From Baseline in DAS28-3 (CRP) at 4, 8 and 12 Weeks [Time Frame: Baseline, Weeks 4, 8 and 12]

Change From Baseline in DAS28-4 (ESR) at 4, 8 and 12 Weeks [Time Frame: Baseline, Weeks 4, 8 and 12]

Percentage of Participants With SDAI Remission (SDAI <=3.3) at 4, 8, and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Number of Participants With Vital Signs Data Meeting Pre-sepcified Criteria [Time Frame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at 4, 8 and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at 4, 8 and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12 [Time Frame: Baseline and Week 12]

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs [Time Frame: Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)]

Percentage of Participants With DAS28-4 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Percentage of Participants With DAS28-4 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Percentage of Participants With Disease Activity Score-28 (4 Components Based on Erythrocyte Sedimentation Rate) (DAS28-4 [ESR]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12 [Time Frame: Baseline and Week 12]

Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12 [Time Frame: Baseline and Week 12]

Change From Baseline in the Patient's Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12 [Time Frame: Baseline, Weeks 4, 8 and 12]

Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12 [Time Frame: Baseline, Weeks 4, 8 and 12]

Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at 4, 8 and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Percentage of Participants With DAS28-3 (CRP) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks [Time Frame: Weeks 4, 8 and 12]

Secondary ID(s)

B7921005

IRAK 4

2016-002337-30

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/02/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02996500