Investigation of Early Structural Changes in Patients with Anklosing Spondyloarthritis

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2010-020077-16-BE
• Date of registration: 17/01/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: Investigation of Early Structural Changes in Patients with Anklosing Spondyloarthritis
• Scientific title: A MULTICENTRE, 12 WEEK DOUBLE BLIND PLACEBO CONTROLLED RANDOMIZED STUDY OF ETANERCEPT ON A BACKGROUND NSAID IN THE TREATMENT OF ADULT SUBJECTS WITH NON RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS WITH A 92 WEEK OPEN LABEL EXTENSION
• Date of first enrolment: 13/07/2011
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020077-16
• 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: yes Other trial design description: Period 1 is controlled, Period 2 is Open-label If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Belgium, Colombia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Korea, Republic of, Netherlands, Spain, Taiwan, United Kingdom

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:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
? 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;
? Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
? Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Diagnosis of axial spondyloarthritis, as defined by the ASAS criteria. Duration of symptoms.of >3 months and <5 years at the time of consent.
2. Active symptoms defined by a BASDAI =4 at the screening visit.
3. Axial symptoms of back pain with a less than favorable response to current intake of an NSAID at the optimal tolerated dose as determined by the investigator. Subjects must have failed at least 2 NSAIDs (including the current one) taken separately at the optimal tolerated dose with a total combined duration of >4 weeks.
4. Subject must be taking a stable dose of an NSAID for at least 14 days before baseline.
5. Female or male 18 years or older but less than 50 years at the time of consent.
6. In the opinion of the investigator, subject is a reasonable candidate for treatment with etanercept.
7. No contraindication to MRI examination (metal implants or inability to lay flat for 30-60 minutes for example).
8. Negative serum pregnancy test taken at screening, negative urine pregnancy test taken at baseline and negative serum pregnancy test collected at baseline.
9. Agreement by male subjects who are not surgically sterile and female subjects who are not surgically sterile or post menopausal to use a highly effective method of birth control for the duration of the study.
10. Ability to self-inject drug or have a designee who can do so.
11. Ability to store injectable test article under refrigerated conditions.
12. Demonstrates an adequate screening for tuberculosis (TB) in accordance with local country guideline.
13. Subject is able to complete health outcomes assessments and test article diary.

Main Inclusion Criteria Period 2
1. Successfully completed Period 1.
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 200
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Any previous treatment with a tumor necrosis factor-alpha (TNF-a) inhibitor, B/T cell inhibitor or other biologic or immunosuppressive agent for a condition other than IBD.
3. Subject is currently being treated or had previous treatment within 6 months for IBD with any tumor necrosis factor-alpha (TNF-a) inhibitor or any other immunosupressant.
4. Any orthopedic or medical condition that can cause chronic back pain (different than SpA) such as spondylodiscitis, tumor or advance discopathy.
5. Evidence of IBD flare within 6 months of baseline.
6. Evidence of current or recent episodes of uveitis within 6 months of baseline.
7. Radiological sacroiliitis grade is 3-4 unilaterally or grade ?2 bilaterally as defined by the NY criteria. Only results from the central imaging reader will determine eligibility. Historical x-rays (obtained within 4 months of screening) may be utilized, however these subjects must exhibit radiological sacroilitis grade 0-1 unilaterally or grade 0 bilaterally.
8. Subject has a known or suspected allergy, hypersensitivity, or contraindication to ETN, its excipients, or other compounds related to this class of medication.
9. Subject has concurrent treatment with more than 1 NSAID within 14 days at baseline. Aspirin use, at daily doses up to 325 mg if indicated for cardiovascular protection is permissible and will not be counted as an additional NSAID.
10. Subject has had the dose of NSAID that changed within 14 days before baseline.
11. DMARDS other than methotrexate, sulfasalazine and hydroxychloroquine within 4 weeks of baseline.
12. Subject has had a dose of prednisone >10 mg/day (or equivalent) or has had a dose changed within 4 weeks before baseline.
13. Subject has received an intra-articular, intravenous, intramuscular, or subcutaneous (SC) corticosteroid within 4 weeks before baseline.
14. Subject is a pregnant or breastfeeding woman.
15. Has current or recent (within 2 years of screening) active TB infection.
? Local country guidelines should be followed for appropriate TB screening in the setting of anti-TNF therapy, including a minimum of a chest radiograph and objective TB testing such as purified protein derivative [PPD] or Quantiferon depending on what is acceptable per local guidelines.
16. Untreated latent TB.
? Subjects with known latent TB infection may be allowed only if local guidelines are followed for prophylactic therapy and if TB chemoprophylaxis has been adequately completed or initiated at least 4 weeks prior to screening.
17. Received TB chemoprophylaxis during screening and has had ALT and/or AST >2x upper limit of normal [ULN] during this period.
? For subjects that have been diagnosed with TB and started chemoprophylaxis during the screening period, additional blood samples for ALT and AST must be drawn between 3- 4 weeks after initiating chemoprophylaxis. The results need to be reviewed prior to randomization.
18. Serious infection (infection associated with hospitalization and/or intravenous antibiotics) within 1 month before test article administration.
19. Active infection at the time of the screening visit and/or the baseline visit. Certain minor active infections (ie, vaginitis, tinea, etc) could be allowed on a case-by-case basis only afte

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

Health Condition(s) or Problem(s) studied

Axial Spondyloarthritis (AxSpA)
MedDRA version: 16.1 Level: PT Classification code 10051265 Term: Spondyloarthropathy System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Trade Name: ENBREL® 50 mg Solution for Injection in Pre-filled Syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ETANERCEPT
CAS Number: 185243690
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)

Timepoint(s) of evaluation of this end point: Week 12 (End of Double Blind Treatment Period)

Primary end point(s): The primary endpoint of this study is the proportion of subjects who achieve ASAS 40 at week 12.

Main Objective: The primary objective of this study is to compare the efficacy of ETN against placebo in improving symptoms of early non-radiographic axial SpA at 12 weeks when added to a background NSAID at the optimal anti-inflammatory dose.

Secondary Objective: 1. To assess the efficacy and safety of ETN + background NSAID over 104 weeks;
2. To compare the effect of ETN 50 mg once weekly versus placebo on inflammation seen in MRI of the spine at 12 weeks when added to a background NSAID at the optimal anti-inflammatory dose;
3. To compare the quality of life between those subjects treated with ETN 50 mg once weekly versus placebo over 12 weeks when added to a background NSAID at the optimal anti-inflammatory dose.

Secondary Outcome(s)

Secondary end point(s): 1. Proportion of subjects who achieve ASAS 40 at time points other than 12 weeks;
2. Proportion of subjects who achieve ASAS 20;
3. Proportion of subjects who achieve ASAS 5/6;
4. Changes from baseline in ASDAS;
5. Proportion of subjects with ASAS partial remission;
6. Time to ASAS partial remission;
7. Changes from baseline in Subject Assessment of Disease Activitiy (VAS);
8. Changes from baseline in the VAS Physician Global Assessment;
9. Changes from baseline in VAS nocturnal and total back pain over time;
10. Changes from baseline in the BASFI and its components;
11. Changes from baseline in the BASDAI and its components;
12. Proportion of subjects who achieved BASDAI 20 and BASDAI 50;
13. Changes in BAS-G;
14. Changes from baseline in spinal mobility as measured by BASMI (and its individual components), and occiput-to-wall distance, and chest expansion;
15. Changes in inflammation at week 12 as measured by MRI of the spine at week 12;
16. Changes from baseline in tender and swollen joint counts (44 count);
17. Changes from baseline on dactylitis and enthesitis score (MASES);
18. Changes from baseline in the acute phase reactants C Reactive Protein (CRP) and Erythrocyte sedimentation rate (ESR);
19. Health Outcomes Assessments using the following instruments: WPAI, HADS, EQ-5D MFI, SF 36, ASQoL, ASWIS, MOS Sleep, MFI, PASS, and MCII.

Timepoint(s) of evaluation of this end point: Secondary endpoints are evaluated at all in clinic study visits (visit 1-16 or early discontinuation)

Secondary ID(s)

2010-020077-16-ES

B1801031

Source(s) of Monetary Support

Pfizer Inc