A Phase 3 Study Of The Efficacy And Safety Of Tofacitinib In Patients With Active Ankylosing Spondylitis (AS)
- Conditions
- Ankylosing spondylitis (AS)MedDRA version: 20.0Level: PTClassification code 10002556Term: Ankylosing spondylitisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-000226-58-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of and is capable of comprehending all pertinent aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Subject is at least 18 years old (or the minimum country-specific age of consent if > 18) at the screening visit.
4. The subject has a diagnosis of AS based on the Modified New York Criteria for Ankylosing Spondylitis (1984).
5. The subject must have a radiograph of the SI joints (AP Pelvis) documenting diagnosis of AS. Previous radiographs (up to 2 years old) can be used if they are accepted by the central reader. Otherwise, a new radiograph will be obtained during the screening period.
6. Subject has active AS Screening and Baseline (Day 1) visits defined as:
• BASDAI score of =4; and
• Back pain score (BASDAI Question 2) of =4.
7. Subject has active disease despite nonsteroidal anti-inflammatory drug (NSAID) therapy or is intolerant to NSAIDs as defined in the protocol. Subjects who are designated as TNFi-IR must have received at least 1, but not more than 2 approved TNF inhibiting biologic agent that was administered in accordance with its labeling recommendations and was inadequately effective after the minimum treatment times listed below and/or not tolerated after one or more doses.
• At least 3 months of adalimumab treatment;
• At least 3 months of etanercept treatment;
• At least 4 infusions of infliximab;
• At least 3 injections of golimumab;
• At least 3 months of certolizumab treatment.
Intolerance is defined as having experienced a treatment-related AE (eg, infusion/injection reactions, infections, laboratory test changes, etc).
8. Subjects may be receiving the following csDMARDs 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 (MTX): Maximum dose of 25 mg/week. Minimum duration of therapy 4 months and dose stable for 4 weeks prior to first dose of investigational product. Subjects on MTX should be on an adequate and stable dose of folate supplementation per local standards/regulatory approval (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 investigational product. Subject must not have had previous serious toxicity while on MTX and not be expected to require evaluation for possible methotrexate toxicity (eg, require a liver biopsy for methotrexate toxicity) during the study;
• Sulfasalazine (Azulfidine®, Salazopyrin®): Maximum dose of 3 gm/day. Minimum duration of therapy 2 months and dose stable for 4 weeks prior to first dose of investigational product.
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 1 week prior to the first dose of investigational product;
• Injected (eg, intraarticular, intramuscular, epidural or intravenous) corticosteroids must be discontinued 4 weeks prior to the first dose of investigational product;
• Topical and intra-rectal corticosteroids will be allowed during th
1. Investigator site staff members directly involved in the conduct of the study 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. Persons who are dependent upon the sponsor, investigator or the study site are excluded.
2. Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation (excluding noninterventional follow-up during the screening period).
3. Other acute or chronic medical or psychiatric condition including recent (within the past year) 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 and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
4. History of known or suspected complete ankylosis of the spine.
5. Subjects that have been exposed to or are currently receiving targeted synthetic DMARDS (including JAK inhibitors), or those currently on biological DMARDs (ie washout from any current bDMARD required per protocol section 5.8.1), thalidomide (including previous use) and other prohibited concomitant medications.
6. History of allergies, intolerance or hypersensitivity to lactose or tofacitinib (CP-690,550). This includes subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. The investigators of potential subjects with acquired lactose intolerance should consider whether this is sufficiently concerning so as to preclude participation.
7. Blood dyscrasias at screening or within 3 months prior to the first dose of investigational product including confirmed:
• Hemoglobin <10 g/dL;
• Absolute white blood cell count (WBC) <3.0 x 10^9/L (<3000 mm3);
• Absolute neutrophil count (ANC) <1.5 x 10^9/L (<1500 mm3);
• Absolute lymphocyte count <1.0 x 10^9/L (<1000/mm3);
• Platelet count <100 x 10^9/L (<100,000/mm3).
8. Estimated Creatinine Clearance <40 mL/min based on Cockcroft Gault equation at Screening visit.
9. Total bilirubin, AST or ALT more than 1.5 times the upper limit of normal (ULN) at screening visit.
One re-testing of a laboratory-acceptable specimen (eg, appropriately labeled, within stability parameters, not hemolyzed, appropriate type (tube and reagent) and volume) is allowed of any above parameters if the abnormal lab(s) was an uncharacteristic result(s). Re-test must be completed within the screening period.
10. History of any other autoimmune rheumatic disease.
11. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
12. History of any lymphoproliferative disorder, such as Epstein Barr Virus related lymphoproliferative disease (EBV-LPD), history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
13. History of recurrent (more than one episode) herpes zoster or disseminated/multi-dermatomal (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
14. History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 3 months prior to the first dose of investigational product.
15. History of infection requi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To compare the efficacy of tofacitinib 5 mg BID versus placebo on the ASAS20 response rate at Week 16 in subjects with active AS that have had an inadequate response to previous treatment.;Secondary Objective: • To compare the efficacy of tofacitinib 5 mg BID versus placebo on the ASAS40 Response rate at Week 16 in subjects with active AS that have had an inadequate response to previous treatment. <br>• To compare the safety and tolerability of tofacitinib 5 mg BID versus placebo in subjects with active AS that have had an inadequate response to previous treatment.<br>• To compare the efficacy (including health related, quality of life, function, pain, and fatigue) of tofacitinib 5 mg BID versus placebo at all time points in subjects with active AS that have had an inadequate response to previous treatment.;Primary end point(s): • ASAS20 response at Week 16.;Timepoint(s) of evaluation of this end point: Week 16
- Secondary Outcome Measures
Name Time Method