A medical research study to evaluate the safety and effectiveness of an investigational medication for rheumatoid arthritis

• Register: EUCTR
• Last refreshed on: 13 November 2017
• Main ID: EUCTR2016-002862-30-SK
• Date of registration: 14/12/2016
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc 235 East 42nd Street, New York, NY10017 US
• Public title: A medical research study to evaluate the safety and effectiveness of an investigational medication for rheumatoid arthritis
• Scientific title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP, PLACEBO-CONTROLLED, MULTI-CENTER STUDY TO ASSESS THE EFFICACY AND SAFETY PROFILE OF PF-06651600 IN SUBJECTS WITH MODERATE TO SEVERE ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
• Date of first enrolment: 16/02/2017
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002862-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Georgia, Germany, Hungary, Poland, Romania, Serbia, Slovakia, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
3. Male and female subjects (including Women of Childbearing Potential (WOCBP)) between the ages of 18 and 75 years, inclusive. For subjects >70 years old, the site must discuss subject eligibility with the study team to ensure that these subjects are sufficiently healthy to participate.
4. Female subjects of childbearing potential must test negative for pregnancy at screening visit and baseline visit.
5. Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:
a. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
6. Diagnosis of rheumatoid arthritis (RA) and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism
classification criteria (see Appendix 2) 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 methotrexate inadequate response (see below).
7. Meets Class I, II or III of the ACR 1991 Revised Criteria for the classification of Global Functional Status in RA (see Appendix 2).
8. 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 High sensitivity C reactive protein (hsCRP) =7 mg/L at screening performed by the central laboratory. Subjects who do not meet this entry criterion but satisfy all other study entry criteria may have serum hsCRP concentration re-tested and, if the repeat hsCRP concentration is =7 mg/L prior to the baseline visit, will be eligible to enroll into the study provided all other inclusion/exclusion criteria are
met.
9. Subjects must be seropositive (rheumatoid factor positive and/or anti-citrullinated protein antibody positive) at the screening visit.
10. 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, defined, for the purpose of this study, by the investigator’s and subject’s opinions that the subject did not experience adequate benefit from methotrexate plus the presence of sufficient residual disease activity to meet the entry criteria. Allowed methotrexate doses are 15 to 25 mg, inclusive, weekly, unless there is documented (in the source documentation) intolerance to or toxicity from these doses, in which case a dose between 10 and <15 mg, inclusive, may be used (See Section 5.8). The dose must have been stable for at least 4 weeks before first dose of study drug, and the dose must remain stable during the study.Subjects should be on an adequate and stable dose of folic acid (not less than 5 mg weekly, unless higher doses would violate the local label) for at least 4 weeks prior to the first dose of investigational product or ora
Exclusion criteria:
1. Investigator site staff members and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study
2. Participation in other studies involving investigational drug(s) within 30 days or 5 half-lives prior to study entry and/or during study participation.
3. Other acute or chronic medical or psychiatric condition including recent or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results.
4. Any major condition or evidence of an unstable clinical condition that will substantially increase the risk to the subject if he or she participates in the study
5. Acute coronary syndrome and any history of cerebrovascular disease within 24 weeks before screening or in the period between the Screening Visit and the Baseline Visit.
6. Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
7. Subjects with acute or active chronic dermatological disorders within 4 weeks prior to study entry or in the period between the Screening Visit and the Baseline Visit
8. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who wish to become pregnant or who are unwilling or unable to use 2 highly effective methods of contraception
9. History of alcohol or drug abuse with less than 6 months of abstinence prior to the Baseline Visit
11. Subjects treated with prohibited medications will be excluded unless appropriate washout has been performed
12. Any current evidence of untreated latent or active TB infection, evidence of currently active TB by chest x-ray, residing with or frequent close contact with individual(s) with active TB.
13. Current routine household contact with children or anyone else who have received varicella or oral polio or any other live vaccine within 6 weeks of first study dose, or during the course of the study
14. Any live vaccines from 30 days prior to the Baseline Visit and through the Follow Up Visit
15. Subjects who have been in contact with people with acute infections within 2 weeks prior to the Screening Visit or in the period between the Screening Visit and the Baseline Visit
16. History of any lymphoproliferative disorder, history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current lymphatic disease
17. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant. Skin grafts are allowed.
18. History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations
19. Subjects with malignancy or history of malignancy, with the exception of subjects with adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ
20. Preexisting chronic autoimmune disease other than RA. Secondary Sjogren’s-Syndrome associated with RA may be included.
21. Major surgery within 4 weeks of the Screening Visit or if scheduled to occur during the study, excluding diagnostic surgical procedures.
22. Previous treatment with total lymphoid irradiation
23. Subjects with any condition possibly affecting oral drug absorption. Proced

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

RHEUMATOID ARTHRITIS
MedDRA version: 20.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Code: PF-06651600
Pharmaceutical Form: Tablet
INN or Proposed INN: not yet assigned
Current Sponsor code: PF-06651600
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Change from baseline in simple disease activity index
(SDAI) at Week 8.

Main Objective: To evaluate the efficacy of PF-06651600
at 8 weeks in subjects with moderate to
severe active RA.

Timepoint(s) of evaluation of this end point: 8 weeks

Secondary Objective: - To evaluate the safety of PF-06651600.
- To assess other signs of clinical efficacy
over 8 weeks.
- To assess the effect of PF-06651600 on
patient reported outcome measurements.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 8 weeks

Secondary end point(s): -Safety and tolerability of PF-06651600 versus placebo;
vital signs, laboratory tests, adverse events (AEs)
including infections, and Serious Adverse Events
(SAEs).
-Change from baseline in SDAI at Weeks 1, 2, 4 and 6.
-Change from baseline in SDAI low disease activity
scale (LDAS) and remission rates at Week 4, Week 6
and Week 8
-Change from baseline in DAS28 LDAS and remission
rates at Week 4, Week 6 and Week 8.
The following will also be calculated at Weeks 1, 2,4, 6
and 8:
-Change from baseline in DAS28-3 (ESR), DAS28-3
(CRP), DAS28 -4 (ESR), and DAS28-4 (CRP).
-Change from baseline in hsCRP.
-Change from baseline in the Tender/Painful and
Swollen Joint Count (28).
-Change from baseline in the Physician’s Global
Assessment of Arthritis.
Change from baseline in the Patient’s Assessment of
Arthritis Pain (VAS) and Patient’s Global Assessment
of Arthritis (VAS) at Weeks 1, 2, 4, 6 and 8.
-Change from baseline in the HAQ-DI at Weeks 1, 2, 4,
6 and 8.

Secondary ID(s)

2016-002862-30-HU

B7981006

Source(s) of Monetary Support

Pfizer Inc.