A clinical study to evaluate the effects and safety of three doses of Tofacitinib (a drug that is being investigated for the treatment of rheumatoid arthritis) in subjects with active Ankylosing spondylitis (AS) (a form of Arthritis)

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2011-005689-39-HU
• Date of registration: 22/05/2013
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York 10017
• Public title: A clinical study to evaluate the effects and safety of three doses of Tofacitinib (a drug that is being investigated for the treatment of rheumatoid arthritis) in subjects with active Ankylosing spondylitis (AS) (a form of Arthritis)
• Scientific title: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY OF THE EFFICACY AND SAFETY OF TOFACITINIB IN SUBJECTS WITH ACTIVE ANKYLOSING SPONDYLITIS (AS)
• Date of first enrolment: 27/06/2013
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005689-39
• 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

Countries of recruitment

Canada, Czech Republic, Germany, Hungary, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Taiwan, 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 (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. Subject is at least 18 years old (20 years old for subjects in Taiwan) at the Screening Visit.
4. The subject has a diagnosis of AS based on the Modified New York Criteria for Ankylosing Spondylitis (1984).
5. Subject has active AS at the Screening and Baseline (Day 1) visits defined as:
• BASDAI score of >=4; and
• Back pain score (BASDAI Question 2) of >=4.
6. Subject has active disease despite concurrent nonsteroidal anti-inflammatory drug (NSAID) therapy or is intolerant to NSAIDs.
7. Subject must have had an adequate trial of at least 2 different oral NSAIDs taken over a total period of 4 weeks.
8. Subjects may be receiving the following traditional DMARDs at the time of the Screening visit. These medications should be continued throughout the entire study and doses should remain unchanged. Any other DMARDs require discussion prior to enrollment with the sponsor for washout timeframe.
• Methotrexate: Maximum dose of 20 mg/week. Minimum duration of therapy 4 months and dose stable for 4 weeks prior to first dose of study drug. Subjects on methotrexate should be on an adequate and stable dose of folate supplementation (eg, not less than 5 mg weekly based on folic acid, unless such doses would violate the local label guidelines or standard of care) for at least 4 weeks prior to the first dose of study drug. Subject must not have had previous serious toxicity while on
methotrexate and not be expected to require evaluation for possible methotrexate toxicity (eg, require a liver biopsy for methotrexate toxicity) during the study; • Sulfasalazine (Azulfidine, Salazpyrin): Maximum dose of 3 gm/day. Minimum duration of therapy 2 months and dose stable for 4 weeks prior to first dose of study drug.
9. Subjects who are already taking oral corticosteroids (not injectables) may participate in the study:
• Oral corticosteroids: Subjects who are already receiving oral corticosteroids must be
on a stable dose of =<10 mg/day of prednisone or equivalent for 4 weeks prior to the first dose of study medication;
• Injected (eg, intraarticular, intramuscular, epidural or intravenous) corticosteroids
must be discontinued 4 weeks prior to the first dose of study medication;
• Topical corticosteroids will be allowed during the study.
10. Subject has discontinued all disallowed concomitant medication for the required time prior to the first dose of study medication and is taking only those concomitant medications in doses and frequency allowed by the protocol.
11. Subjects who are receiving any investigational or marketed treatment for AS, arthritis or back pain not mentioned elsewhere must have that treatment discontinued for 4 weeks or 5 half-lives, whichever is longer.
12. Subjects receiving non-prohibited concomitant medications for any reason must be willing to stay on a stable regimen as defined in the protocol.
13. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined in protocol.
14. Women of childbearing potential must test negative for pregnancy prior to enrollment in this study.
15. Female subjects who are not of childbearing potential (ie, meet
Exclusion criteria:
1. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Participation in other interventional studies within 4 weeks before the current study begins and/or during study participation. 3. Subjects receiving any other DMARDs (other than those allowed), thalidomide (including previous use).
4. Subjects currently receiving or previous use of a TNF inhibitor or other biological agent.
5. Blood dyscrasias at screening or within 3 months prior to the first dose of study drug including confirmed:
a. Hemoglobin <10 g/dL;
b. Absolute white blood cell count (WBC) <3.0 x 10 9/L (<3000 mm3);
c. Absolute neutrophil count (ANC) <1.2 x 10 9/L (<1200 mm3);
d. Absolute lymphocyte count <0.5 x 10 9/L (<500/mm3);
e. Platelet count <100 x 10 9/L (<100,000/mm3).
One re-testing of an uncompromised sample (eg, not out of stability, not hemolyzed) is allowed of any above parameters if the abnormal lab(s) was an uncharacteristic result(s). Documentation in the source of the typical results to allow a repeat lab is required.
Re-test must be completed within the screening period.
6. Estimated Creatinine Clearance <40 ml/min based on Cockcroft Gault equation at Screening visit.
7. Total bilirubin, AST or ALT more than 1.5 times the upper limit of normal at screening visit. (One re-testing with an uncompromised sample is allowed if the abnormal lab result was an uncharacteristic result and must be completed within the screening period. Documentation in the source of the typical results to allow a repeat lab is required).
8. History of any other autoimmune rheumatic disease (eg, systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, polymositis) or known diagnosis of fibromyalgia, without approval by Sponsor.
9. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
10. History of any lymphoproliferative disorder, such as Epstein Barr Virus related
lymphoproliferative disorder (EBV-LPD), history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
11. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
12. 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.
13. History of infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study medication.
14. Any prior treatment with alkylating agents (eg, cyclophosphamide or chlorambucil), total lymphoid irradiation, etc. 15. Any subject who has been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study medication or is to be vaccinate with these vaccines at any time during treatment or within 6 weeks after last dose of study drug.
16. A subject with any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary. 17. History of alcohol or drug abuse unless in full remission for greater than 6 months prior to first

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

Health Condition(s) or Problem(s) studied

Ankylosing Spondylitis (AS)
MedDRA version: 17.1 Level: PT Classification code 10002556 Term: Ankylosing spondylitis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Product Name: CP-690,550-10
Product Code: CP-690,550-10
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tofacitinib
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550-10
Other descriptive name: TOFACITINIB CITRATE
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

Product Name: CP-690,550-10
Product Code: CP-690,550-10
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tofacitinib
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550-10
Other descriptive name: TOFACITINIB CITRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 1. To compare the efficacy of tofacitinib, in doses of 2 mg BID, 5 mg BID, 10 mg BID versus placebo on the ASAS20 response rate at Week 12 in subjects with active AS that have had an inadequate response to previous treatment.
2. To estimate the placebo-corrected dose response for the ASAS20 at Week 12 in subjects with active AS that have had an inadequate response to previous treatment.
3. To compare the safety of tofacitinib at all doses versus placebo in all study subjects.

Timepoint(s) of evaluation of this end point: Week 12

Primary end point(s): - ASAS 20 response rate

Secondary Objective: None

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 2, 4, 8, 12

Secondary end point(s): A validated endpoint such as Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score and/or modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the SI joints and spine at Week 12.
•ASAS20 response at all other time points.
•ASAS40 response at all time points.
•ASAS 5/6 response at all time points.
•Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein
(ASDASCRP) at all time points.
•ASDAS clinically important improvement, ASDAS major improvement and ASDAS inactive disease at all time points.
•Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at all time points.
•BASDAI50 response at all time points.
•Bath Ankylosing Spondylitis Functional Index (BASFI) at all time points.
•Bath Ankylosing Spondylitis Metrology Index (BASMI) at all time points.
•Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at all time points collected.
•Extra-articular Involvement (Specific Medical History and peripheral articular involvement [as assessed by swollen joint count]) at all time points collected.
•Spinal mobility at all time points collected.

Secondary ID(s)

A3921119

Source(s) of Monetary Support

Pfizer Inc