A Phase 3 Study Of The Efficacy And Safety Of Tofacitinib In Patients With Active Ankylosing Spondylitis (AS)

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2018-000226-58-ES
• Date of registration: 09/05/2018
• 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 Tofacitinib In Patients With Active Ankylosing Spondylitis (AS)
• Scientific title: A Phase 3, Randomized, Double Blind, Placebo Controlled, Study Of The Efficacy And Safety Of Tofacitinib In Subjects With Active Ankylosing Spondylitis (AS)
• Date of first enrolment: 04/07/2018
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000226-58
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Open label treatment phase from Week 16 - 48 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): no

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Korea, Republic of, Poland, Russian Federation, Slovakia, Spain, Taiwan, Turkey, Ukraine, 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:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) 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. 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. 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 at the Screening visit.
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
8. 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)
9. 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 20 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®, Salazpyrin®): 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.
10. 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
Exclusion criteria:
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.
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. This can be determined/confirmed at the time of the SI radiograph by the central reader.
5. Subjects receiving any other conventional synthetic or biological DMARDs (other than those allowed), thalidomide (including previous use) and other prohibited concomitant medications.
6. Subjects that have been exposed to biological DMARDs other than TNF inhibitors.
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). Documentation in the source of the typical results to allow a repeat lab is required.
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 requiring antimicr

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

Health Condition(s) or Problem(s) studied

Ankylosing spondylitis (AS)
MedDRA version: 20.0 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)

Trade Name: Xeljanz
Product Name: Tofacitinib 5 mg
Product Code: CP-690,550
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

Primary Outcome(s)

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.

Primary end point(s): • ASAS20 response at 16 weeks.

Secondary Objective: • 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.
• To compare the efficacy 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
• To measure the effect of tofacitinib 5 mg BID on the quality of life and functional well-being at all collected time points.

Timepoint(s) of evaluation of this end point: 16 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At all timepoints. Please refer to the protocol for additional details

Secondary end point(s): • Incidence and severity of Adverse Events (AE).
• Clinical laboratory tests, vital signs, physical examination and 12-lead ECG parameters.
• ASAS40 response at all time points.
• ASAS20 response at all other time points.
• ASAS 5/6 response at all time points.
• Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein (ASDASCRP) at all time points.
• hsCRP.
• 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.
• ASAS partial remission criteria at all time points.
• Short-Form-36 Health Survey (SF-36) Version 2, Acute at all time points collected.
• EuroQol EQ-5D Health State Profile (EQ-5D) and Your own health state today (EQ-VAS), at all time points collected.
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at all time points.
• Ankylosing Spondylitis Quality of Life (ASQoL) at all time points collected.
• Work Productivity and Activity Impairment (WPAI) Questionnaire: Spondyloarthritis at all time points collected
• AS HealthCare Resource Utilization Questionnaire (AS-HCRU) at all time points collected.

Secondary ID(s)

A3921120

2018-000226-58-HU

Source(s) of Monetary Support

Pfizer Inc

Ethics review

Status: Approved
Approval date:
Contact: