Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Ankylosing Spondylitis (AS) - START - Spondylitis Trial of Apremilast for better Rheumatic Therapy

Active, not recruiting

• Conditions: Ankylosing Spondylitis; MedDRA version: 9.1Level: LLTClassification code 10002556Term: Ankylosing spondylitis

• Registration Number: EUCTR2008-004229-40-GB
• Lead Sponsor: Imperial College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-22
• Last Update Posted: 2012-03-19

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

a) Written informed consent to participate in this trial

b) Diagnosis of ankylosing spondylitis as defined by the modified New York criteria (1984) as follows:

(1) a history of inflammatory back pain;
(2) limitation of motion of the lumbar spine in both the sagittal and frontal planes;
(3) limited chest expansion, relative to standard values for age and sex;
(4) definite radiographic / imaging evidence of sacroiliitis and/or spinal inflammation

c) Patients must have daily spinal pain and stiffness for at least 2 weeks prior to randomization. This is defined by having a score of >1 on questions #2 and #5 of the BASDAI score for the 2 weeks prior to randomization.

d) Patients receiving NSAIDS and/or COX-2 inhibitors must be on stable doses for at least 2 weeks prior to randomization.

e) Age >18 years.

f) Male and female patients, who are not surgically sterile or postmenopausal, must use reliable methods of birth control for the duration of the study. Males must agree to use barrier contraception for 3 months following the end of the trial.

g) Women of childbearing potential, not surgically sterile or postmenopausal, must have a negative serum beta HCG.

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

a) Use of DMARDs (methotrexate, d-penicillamine, sulfasalazine, azathioprine,
hydroxychloroquine, or gold) within 8 weeks of randomization.

b) Use of systemic corticosteroids within 4 weeks of randomization.

c) Use of intravenous or intra-articular corticosteroids within 4 weeks of randomization.

d) Use of TNF alpha blockers eg, infliximab (within 12 weeks), adalimumab (within 10 weeks) or etanercept (within 4 weeks).

e) Therapy with an investigational agent within 30 days of randomization or 5 half-lives (pharmacokinetic or pharmacodynamic), which ever is longer.

f) Known HIV or hepatitis B or C infection.

g) Exclusion of tuberculosis (TB).

• History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit.
Infections that occurred > 3 years prior to entry must have been effectively treated.
• History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein
Derivative [PPD] skin test)
• Clinically significant abnormality on chest x-ray (CXR)if Mantoux is greater than 5 mm or ELISPOT positive.

h) History of other rheumatic autoimmune diseases (eg, systemic lupus erythematosus, rheumatoid arthritis, etc.)

i) Pregnant or nursing women

j) Any condition, in the investigator's opinion, which places the patient at an undue risk by participating in the study.

k) Contraindication to MRI and other MRI exclusions following local centre guidelines (Appendix H)

l) An estimated glomerular filtration rate (eGFR) of < 60 ml/min (because of the small risk of nephrogenic sclerosing.

fibrosis with gadolinium intravenous contrast).

m) Claustrophobia.

n) Hemoglobin < 9 g/dL.

o) White blood cell (WBC) count < 3000 /µL ( 3.0 X 109/L) and 14,000/µL ( 20 X 109/L).

p) Neutrophils < 1500 /µL (< 1.5 X 109/L).

q) Platelets < 100,000 /µL (< 100 X 109/L).

r) Serum creatinine > 1.5 mg/dL (> 132.6 µmol/L).

s) Total bilirubin > 2.0 mg/dL.

t) Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT
[serum glutamate pyruvic transaminase, SGPT]) > 1.5x upper limit of normal (ULN).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): To investigate changes in MRI of the spine and sacro-iliac joints pre and post apremilast compared to placebo and to examine the effects on signs and symptoms of the disease. ;Main Objective: To demonstrate the effect of apremilast on magnetic resonance imaging lesions in ankylosing spondylitis.<br><br>To explore the effect of apremilast on the signs and symptoms of ankylosing spondylitis.<br><br>;Secondary Objective: To explore the safety and tolerability of apremilast in ankylosing spondylitis.