A Randomised, Double-Blind Study Comparing the Safety and Efficacy of Etanercept with Sulphasalazine in Subjects with Ankylosing Spondylitis - ASCEND

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-001549-41-GB
• Date of registration: 29/11/2005
• Prospective Registration: Yes
• Primary sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc
• Public title: A Randomised, Double-Blind Study Comparing the Safety and Efficacy of Etanercept with Sulphasalazine in Subjects with Ankylosing Spondylitis - ASCEND
• Scientific title: A Randomised, Double-Blind Study Comparing the Safety and Efficacy of Etanercept with Sulphasalazine in Subjects with Ankylosing Spondylitis - ASCEND
• Date of first enrolment: 02/02/2006
• Target sample size: 540
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-001549-41
• 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: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes

Countries of recruitment

Austria, Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Italy, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subject must fulfil all of the following conditions or characteristics in order to be considered for study enrolment:
1. Diagnosis of AS, as defined by Modified New York Criteria for Ankylosing Spondylitis (Attachment 1).
2. Active AS, defined on a scale of 0 to 100 by:
· BASDAI visual analogue scale nlt 30;
. Average duration and intensity of morning stiffness visual analogue scale (VAS) of nlt 30;
· At least 2 of the following:
- Patient global assessment VAS nlt 30 (Attachment 6);
- Average nocturnal and total pain VAS nlt 30 (Attachment 7);
- Bath Ankylosing Spondylitis Functional Index (BASFI; Attachment 3) VAS nlt 30.
3. In the opinion of the investigator, subject is a reasonable candidate for treatment with SSZ (for example, this may be the presence of peripheral joint symptoms) and ETN.
4. Treatment failure to at least one NSAID of at least three months duration at the maximal recommended or tolerated anti-inflammatory dose, unless NSAIDs are contraindicated.
5. 18 years of age or older at time of consent.
6. Negative serum pregnancy test taken at screening in all women except those who were surgically sterile or at least 1 year postmenopausal. Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception (which include oral contraception, injectable or implantable methods, intrauterine devices, or properly used barrier contraception). A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
7. Agreement by male subjects who are not surgically sterile and female subjects who are not surgically sterile or postmenopausal to use reliable methods of birth control for the duration of the study.
8. Ability to self-inject drug or have a designee who can do so.
9. Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed.
10. Ability to store injectable test article at 2°C to 8°C.


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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects with any of the following conditions or characteristics will be excluded from study enrolment:
1. Complete ankylosis (fusion) of spine.
2. Previous treatment with etanercept, antibody to tumour necrosis factor a (TNFa), or other TNFa inhibitors or other biologic agents.
3. Treatment with SSZ within 6 months of screening.
4. History of treatment with SSZ associated with significant toxicity or significant lack of response.
5. Contraindication to SSZ including:
· Hypersensitivity to SSZ, its metabolites, sulfonamides, or salicylates
. Known history of glucose-6-phosphate dehydrogenase deficieny
· History or presence of intestinal or urinary obstruction
· History or presence of porphyria
· Current treatment with digoxin
6. Failure to respond to treatment to more than one DMARD.
7. Use of DMARDs other than methotrexate or hydroxychloroquine within 4 weeks of baseline. Subjects on methotrexate or hydroxychloroquine must have been on a stable dose for at least 4 weeks prior to randomisation.
8. Receipt of more than one DMARD concurrently at screening.
9. Previous use of intravenous bisphosphonate.
10. Receipt of more than one NSAID concurrently at baseline.
11. Dose of NSAID changed within 2 weeks of baseline.
12. Dose of prednisone >10 mg/day (or equivalent) or changed within 2 weeks of baseline.
13. Receipt of intra-articular, intravenous, intramuscular, or subcutaneous corticosteroid within 4 weeks of screening.
14. Abnormality in haematology or chemistry profiles: haemoglobin nmt 85 g/L; haematocrit nmt 27%; platelet count nmt 125 x 10 power 9 /L; white blood cell count nmt 3.5 x 10 power 9 /L; serum creatinine nlt 175 mmol/L; aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) nlt 2 times the laboratory’s upper limit of normal.
15. Significant concurrent medical events including:
· Uncontrolled hypertension (defined as screening systolic blood pressure > 160 mm Hg or screening diastolic blood pressure > 100 mm Hg)
· Myocardial infarction within 12 months of the screening visit
· Unstable angina pectoris
· Class III or IV congestive heart failure as defined by the New York Heart Association classification (16) or uncompensated congestive heart failure
· Severe pulmonary disease requiring hospitalisation or supplemental oxygen
· Diagnosis of multiple sclerosis or other central demyelinating diseases
· Presence or history of confirmed blood dyscrasias
· Uncontrolled diabetes mellitus
· Rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or polymyositis
· Cancer or history of cancer (other than resected cutaneous basal cell or squamous cell carcinoma)
· Serious infection (infection associated with hospitalisation and/or intravenous antibiotics) within 1 month of test article administration or active infection at screening, or history of recurrent or chronic infection
· Open cutaneous ulcers
· Known human immunodeficiency virus (HIV), hepatit

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

Health Condition(s) or Problem(s) studied

Subjects with Ankylosing Spondylitis (AS)

Intervention(s)

Trade Name: Enbrel (etanercept)
Product Name: Etanercept
Product Code: 0881
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Etanercept
Current Sponsor code: 0881
Other descriptive name: TNR-001; TNFR:Fc; rhuTNFR:Fc
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 50-
Pharmaceutical form of the placebo: Powder and solvent for solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Salazopyrin En-Tabs
Product Name: sulphasalazine 500 mg En-Tabs
Product Code: SSZ
Pharmaceutical Form: Coated tablet
INN or Proposed INN: sulphasalazine
Other descriptive name: sulfasalazine, SSZ
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint will be the proportion of subjects who achieve ASAS 20 at Week 16 relative to baseline.

Main Objective: To compare the efficacy of etanercept 50 mg once weekly with SSZ 3 g daily in the treatment of AS subjects over 16 weeks. The study hypothesis is that etanercept 50 mg once weekly will demonstrate superior clinical efficacy, as determined by the proportion of responders achieving a 20% improvement on the Assessment of AS (ASAS) response criteria (ASAS 20; Attachment 2) at 16 weeks, compared with SSZ 3 g daily in the treatment of AS subjects.

Secondary Objective: 1. To compare the effect of etanercept 50 mg once weekly with SSZ 3 g daily on the quality of life over 16 weeks.
2. To evaluate the safety of etanercept 50 mg once weekly over 16 weeks.

Secondary ID(s)

0881A3-402-WW

2005-001549-41-HU

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 28/01/2015
• Date Completed: 01/02/2008
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-001549-41/results