A PHASE 3B/4 STUDY OF METHOTREXATE (MTX) WITHDRAWAL IN SUBJECTS WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH TOFACITINIB 11MG

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-001825-15-PL
• Date of registration: 08/03/2017
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, New York
• Public title: A PHASE 3B/4 STUDY OF METHOTREXATE (MTX) WITHDRAWAL IN SUBJECTS WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH TOFACITINIB 11MG
• Scientific title: A PHASE 3B/4 RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED STUDY OF METHOTREXATE (MTX) WITHDRAWAL IN SUBJECTS WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH TOFACITINIB 11MG MODIFIED RELEASE (MR) FORMULATION
• Date of first enrolment: 29/03/2017
• Target sample size: 680
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001825-15
• 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): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Belgium, Bulgaria, Czech Republic, Germany, Hungary, Italy, Korea, Republic of, Mexico, Philippines, Poland, Russian Federation, Slovakia, South Africa, Spain, United Kingdom, 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:
Key Inclusion Criteria
- Must be 18 years of age or older.
Have a score of 6 or greater on the 2010 American College of Rheumatology/European League Against Rheumatism Classification
Criteria for Rheumatoid Arthritis at and/or prior to Screening Visit.
•Have =4 tender/painful joints on motion and =4 swollen joints (28 joint counts) at both Screening Visit and Baseline Visit (Visit 1).
•Have moderate to severe disease activity as defined by CDAI>10 and DAS28-4(ESR) =3.2 at Baseline Visit.
•Have taken an oral MTX treatment regimen (15-25mg/week) continuously for at least 4 months prior to the screening visit and has taken a stable weekly dose of oral MTX with supplemental folic acid or folinic acid for at least 4 weeks prior to the baseline visit (conversion from parenteral MTX to oral MTX will require stabilization of the treatment regimen for at least 1 month).
•Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use highly effective contraception throughout the study and for at least 6 months after the last dose of assigned treatment.
•Subjects must screen negative for active tuberculosis or inadequately treated tuberculosis infection (active or latent).
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 528
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 152

Exclusion criteria:
Key Exclusion Criteria
•Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use highly effective contraception as outlined in this protocol for the duration of the study and for at least 6 months after the last dose of investigational product.
•Subjects with infection or infection history; subjects with any current malignancy or a history of malignancy (except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ); subjects with history of, or current evidence for, severe gastrointestinal narrowing (pathologic or iatrogenic); and subjects with history of documented diverticulitis.
•Subjects with a history of insufficient response to =2 biologics, regardless of the class.
•Subjects screened in Belgium, Czech Republic, Germany, Hungary, Italy, Poland, Spain, and the United Kingdom who have resided or traveled in areas with endemic tuberculosis or endemic mycoses will be excluded.


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Rheumatoid Arthritis
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: tofacitinib
Product Code: CP 690,550
Pharmaceutical Form: Modified-release tablet
INN or Proposed INN: tofacitinib
CAS Number: 540737-29-9
Current Sponsor code: CP 690,550
Other descriptive name: TOFACITINIB CITRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 11-

Trade Name: Methotrexate 2.5mg Tablets BP
Product Name: methotrexate
Pharmaceutical Form: Capsule
INN or Proposed INN: METHOTREXATE
Other descriptive name: METHOTREXATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Change in DAS28-4 (ESR) score from randomization (at Week 24) to the end of doubleblind MTX withdrawal phase (at Week 48).

Main Objective: To compare the efficacy of tofacitinib MR 11mg monotherapy to tofacitinib MR 11mg with continued MTX, as measured by the change in the Disease Activity Score utilizing 4 components including erythrocyte sedimentation rate (DAS28-4 (ESR)) from randomization (at Week 24) to the end of the double-blind MTX withdrawal phase (at Week 48).

Secondary Objective: •To compare the efficacy of tofacitinib MR 11mg monotherapy to tofacitinib MR 11mg with continued MTX in the double-blind MTX withdrawal phase (at Week 36), as measured by DAS28-4 (ESR).
•To compare the efficacy of tofacitinib MR 11mg monotherapy to tofacitinib MR 11mg with continued MTX in the double-blind MTX withdrawal phase (at Weeks 48 and 36), as measured by Disease Activity Score 28-4 (C reactive protein) (DAS28-4 (CRP)), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Low Disease Activity (LDA), remission, ACR20, ACR 50, and ACR 70.
•To compare effects of tofacitinib MR 11mg monotherapy to tofacitinib MR 11mg with continued MTX on health outcome measures in the double-blind MTX withdrawal phase (at Weeks 48 and 36).
•To evaluate the safety and tolerability of tofacitinib MR 11mg monotherapy versus tofacitinib MR 11mg with continued MTX.

Timepoint(s) of evaluation of this end point: From week 24 to week 48

Secondary Outcome(s)

Secondary end point(s): •Change in the DAS28-4(ESR) from Week 24 to Week 36;
•Changes in the DAS28-4 (CRP), CDAI and SDAI, respectively, from Week 24 to Week 48 and from Week 24 to Week 36;
•LDA as assessed by DAS28 4(ESR) = 3.2, DAS28-4(CRP) = 3.2, CDAI=10 and SDAI=11, respectively, at Weeks 48 and 36;
•Remission as assessed by ACR-EULAR Boolean remission criteria,11 DAS28 4 (ESR)<2.6, DAS28 4 (CRP)<2.6, CDAI=2.8 and SDAI=3.3, respectively, at Weeks 48 and 36;
•ACR20, ACR 50, and ACR70 responses, respectively, at Weeks 48 and 36;
•Change in the HAQ-DI, the SF-36 (8 domain scores and 2 component scores), WPAI, EuroQol EQ-5D and the FACIT-Fatigue scale score, respectively, from Week 24 to Week 48 and from Week 24 to Week 36;
•HAQ-DI response (ie, decrease of at least 0.22) at Weeks 48 and 36.

Timepoint(s) of evaluation of this end point: From week 24 to week 48

Secondary ID(s)

NCT02831855

A3921192

2016-001825-15-SK

Source(s) of Monetary Support

Pfizer Inc.

Ethics review

Status: Approved
Approval date:
Contact: