A PHASE 3 STUDY OF THE EFFICACY AND SAFETY OF 2 DOSES OF TOFACITINIB (CP-690,550) OR ADALIMUMAB IN SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS.

• Register: EUCTR
• Last refreshed on: 25 January 2016
• Main ID: EUCTR2011-003668-55-HU
• Date of registration: 03/09/2013
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A PHASE 3 STUDY OF THE EFFICACY AND SAFETY OF 2 DOSES OF TOFACITINIB (CP-690,550) OR ADALIMUMAB IN SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS.
• Scientific title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF 2 DOSES OF TOFACITINIB (CP-690,550) OR ADALIMUMAB IN SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS. Paediatric investigation plan numbers - (P/144/2010),(P/162/2011) and (P/0064/2012). - OPAL Broaden
• Date of first enrolment: 30/10/2013
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003668-55
• 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: yes Placebo: yes Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Australia, Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Hungary, Mexico, Poland, Russian Federation, Slovakia, Spain, Taiwan, United Kingdom, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. The subject has signs and symptoms consistent with the diagnosis of PsA for at least 6 months and fulfills CASPAR Criteria17 at screening and has evidence of active arthritis based upon number of tender/painful and swollen joints.
4. Ongoing treatment with a stable dose of traditional non-biologic DMARDs (eg, methotrexate, sulfasalazine or leflunomide) (Background DMARDs section, as per protocol).
5. Meet all other eligibility criteria described in Sections A3921091 Specific PsA Patient Population, and the Other Inclusion Criteria section, in the Protocol.
6. Must have inadequate response to a traditional oral non-biologic DMARD.
7. Must be naive to tumour-necrosis factor inhibitor.
Please see the Protocol for the full list of the inclusion criteria.
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 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
Subjects presenting with any of the following will not be included in the study:
1. Currently have non plaque forms of psoriasis, eg erythrodermic, guttate or pustular, with the exception of nail psoriasis, which is allowed.
2. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
3. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks before the current study begins and/or during study participation. Participation in any observational studies during study participation.
4. Pregnant females, breastfeeding females, females of child bearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least one ovulatory cycle after last dose of investigational product or females planning pregnancy. Women of childbearing potential must test negative for pregnancy prior to enrollment in this study. (Further description of the requirements and a list of contraceptives considered highly effective and acceptable for use in this study).
5. Current or recent history of a severe, progressive or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic (including hypercholersterolemia), endocrine, pulmonary, cardiovascular, or neurologic disease.
6. Blood dyscrasias within 3 months prior to the first dose of study drug including confirmed:
a. Hemoglobin <10 g/dL;
b. White blood cell count <3.0 x 10x9/L (<3000/mm3);
c. Absolute neutrophil count =1.5 x 10x9/L(<1500/mm3);
d. Absolute lymphocyte count <1.0x10x9/L (<1000/mm3)
e. Platelet count <100 x 10x9/L (<100,000/mm3).
7. Estimated Creatinine Clearance <40 ml/min based on Cockcroft Gault equation (see Appendix 2).
8. Total bilirubin, AST or ALT more than 1.5 times the upper limit of normal at screening visit.
9. Have a known immunodeficiency or a first degree relative with a hereditary immunodefiency.
10. Also excluded are subjects with history of any autoimmune rheumatic disease other than PsA (including systemic lupus erythematosis, mixed connective tissue disease, scleroderma, polymyositis) or known diagnosis of fibromyalgia, without approval by Sponsor. Prior history of, or current rheumatic inflammatory disease other than PsA (eg, gout, reactive arthritis, chronic Lyme disease) without approval by Sponsor.
11. Functional Class IV as defined by the American College of Rheumatology classification of functional status for RA, ie, limited in ability to perform usual self care, vocational and avocational activities.
12. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
13. History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
14. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
15. History of infection requiring:
• Hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study medication.
• Oral antimicrobial therapy within 2 weeks prior to the fi

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

Health Condition(s) or Problem(s) studied

Psoriatic arthritis (PsA)
MedDRA version: 17.1 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 100000004859

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

Intervention(s)

Product Name: Tofacitinib
Product Code: CP-690,550
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tofacitinib
CAS Number: 477600-75-2
Current Sponsor code: CP-690,550
Other descriptive name: CP-690,550-10
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Humira® 40 mg/0.8 ml solution for injection in pre-filled syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Adalimumab
CAS Number: 331731-18-1
Other descriptive name: Humira
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Humira® 40 mg/0.8 ml solution for injection in pre-filled syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Other descriptive name: Humira
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Primary Efficacy Endpoints:
• ACR20 responder rates at 3 months;
• HAQ DI at 3 months

Timepoint(s) of evaluation of this end point: As above

Secondary Objective: 1. To estimate the difference between tofacitinib and adalimumab at Month 12 in the mean change from baseline in modified Total Sharp Score (?mTSS).
2. To estimate the difference in the rate of progressors (defined as ?mTSS >0.5) between tofacitinib and adalimumab at Month 12.
3. To compare efficacy of tofacitinib at doses of 5 mg BID and 10 mg BID versus placebo on all health outcomes measures as appropriate for the specific outcome.
4. To compare the efficacy of tofacitinib at doses of 5 mg BID and 10 mg BID versus placebo for the treatment of dermatological signs and symptoms of PsA in subjects with active PsA.
5. To compare the efficacy of adalimumab 40 mg SC q 2 weeks versus placebo for the treatment of rheumatologic and dermatologic signs and symptoms of PsA, in subjects with active PsA.

Please see the Protocol for the full list of the secondary objectives.

Main Objective: 1. To compare the efficacy of tofacitinib at doses of 5 mg BID and 10 mg BID versus placebo for the treatment of rheumatological signs and symptoms of PsA, in subjects with active PsA who have had an inadequate response to a traditional non biologic Disease Modifying Anti Rheumatic Drug (DMARD).
2. To compare physical function status of subjects with active PsA who have had an inadequate response to a traditional non biologic Disease Modifying Anti Rheumatic Drug (DMARD) after administration of tofacitinib at doses of 5 mg BID and 10 mg BID versus placebo.
3. To compare the safety and tolerability of two doses (5 mg BID and 10 mg BID) of tofacitinib versus placebo in subjects with active PsA who have had an inadequate response to a traditional non biologic Disease Modifying Anti Rheumatic Drug (DMARD).

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints:
Radiographic Changes
• Total Sharp Score (?mTSS) at Month 12
• Progressor rates (defined as ?mTSS >0.5) at Month 12
Signs and Symptoms
• ACR (American College of Rheumatology) 50 (ACR50) and ACR70 responder rates at all timepoints;
• ACR20 responder rates at all timepoints other than Month 3;
• ACR response criteria components (Health Assessment Questionnaire-Disability Index (HAQ DI), C-reactive Protein (CRP), Patient assessment of Arthritis Pain, Patient Global Assessment of Arthritis, Physcian’s Global Assessment of Arthritis; swollen joint count, tender/painful joint count) at Month 3;
• Psoriatic Arthritis Response Criteria (PsARC) at all timepoints
• Physician’s Global Assessment of Psoriasis (PGA PsO) response at Months 1, 3, 6, 9, and 12;
• Psoriasis Area and Severity Index 75 (PASI75) response at Months 1, 3, 6, 9, and 12;
• Dactylitis severity score at Months 1, 3, 6, 9, and 12;
• Enthesitis (using the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index and Leeds index) at Months 1, 3, 6, 9, and 12.
Secondary Physical Function and Health Outcome Measures
Assessed at Baseline, Months 1, 3, 6, 9, and 12
• Short Form 36 Health Survey (SF 36) Version 2, Acute;
• EuroQol 5 Dimension Health State Profile (EQ5D);
• Functional Assessment of Chronic Illness Therapy Fatigue (FACIT F);
• Evaluation of spondylitis using Bath Anklyosing Spondylitis Disease Assessment Index (BASDAI) and Ankylosing Spondylitis Quaility of Life (ASQOL) questionnaire.
Secondary Safety Endpoints
• Incidence and severity of adverse events;

Other Endpoints
Other Efficacy Endpoints for Signs and Symptoms
• American College of Rheumatology (ACR) response criteria components (Health Assessment Questionnaire-Disability Index (HAQ DI), C-reactive Protein (CRP), Patient assessment of Arthritis Pain, Patient Global Assessment of Arthritis, Physcian’s Global Assessment of Arthritis; swollen joint count, tender/painful joint count) at all timepoints except Month 3;
• DAS28 3(CRP) at all timepoints;
• Psoriatic Arthritis Joint Activity Index (PsAJAI) and Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis (DAREA/DAPSA), Psoriatic Arthritis Disease Severity Score (PASDAS), Composite Psoriasis Disease Activity Index in Psoriatic Arthritis (CPDAI), Minimal Disease Activity (MDA) , and their components at Months 1, 3, 6, 9, and 12;
• PASI and PASI component scores at Months 1, 3, 6, 9, and 12;
• NAPSI at Months 1, 3, 6, 9, and 12;
• Presence of dactylitis at Months 1, 3, 6, 9, and 12;
Physical Function and Health Outcome Measures
Assessed at Baseline, Months 1, 3, 6, 9, and 12
• Patient’s Global Joint and Skin Assessment (PGJS VAS);
• Dermatology Life Quality Index (DLQI);
• Itch Severity Index (ISI);
• Ankylosing Spondylitis Quaility of Life (ASQOL) questionnaire.
Assessed at Baseline, Months 3, 6, 9, and 12:
• PsA Healthcare Resource Utilization Questionnaire (PsA HCRU);
• Work Limitations Questionnaire (WLQ).
Other Safety Endpoints
• Laboratory safety data (clinical chemistry, hematology, etc);
• Physical examinations;
• ECG measurements;
• Vital sign measurements (blood pressure, pulse rate and temperature);
Pharmacokinetic Endpoint
• Oral clearance (CL/F) and other PK parameters calculated from plasma tofacitinib concentrations, if applicable.

Timepoint(s) of evaluation of this end point: As above.

Secondary ID(s)

2011-003668-55-BE

A3921091

Source(s) of Monetary Support

Pfizer Inc