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)
- Written informed consent to participate in this trial
- 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
3. limited chest expansion, relative to standard values for age and sex;
4. definite radiographic / imaging evidence of sacroiliitis and/or spinal
- 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.
- Patients receiving NSAIDS and/or COX-2 inhibitors must be on stable doses for at
least 2 weeks prior to randomization.
- Age >18 years
- 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.
- Women of childbearing potential, not surgically sterile or postmenopausal, must have
a negative serum beta HCG.
- Use of DMARDs (methotrexate, d-penicillamine, sulfasalazine, azathioprine,
hydroxychloroquine, or gold) within 8 weeks of randomization.
- Use of systemic corticosteroids within 4 weeks of randomization
- Use of intravenous or intra-articular corticosteroids within 4 weeks of randomization
- Use of TNF alpha blockers (eg, infliximab, adalimumab) or etanercept as follows:
Compound PK Exclusion period Etanercept T ½ = 102 hrs =
4.25 days 4 weeks Adalimumab T ½ 2 wks; 5 half lives 10 weeks 10 weeks
Infliximab T ½ 7.7-9.5 d 12 weeks 8 weeks after maintenance dose
median infx conc 0.5-6 mcg/ml
- Therapy with an investigational agent within 30 days of randomization or 5 half-lives
(pharmacokinetic or pharmacodynamic), which ever is longer
- Known HIV or hepatitis B or C infection
- 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 >5mm or
- History of other rheumatic autoimmune diseases (eg, systemic lupus erythematosus,
rheumatoid arthritis, etc.)
- Pregnant or nursing women
- Any condition, in the investigator's opinion, which places the patient at an undue
risk by participating in the study.
- Contraindication to MRI and other MRI exclusions following local centre guidelines
- An estimated glomerular filtration rate (eGFR) of < 60 ml/min (because of the small
risk of nephrogenic sclerosing fibrosis with gadolinium intravenous contrast), if
patient is to have MRI with gadolinium contrast .
- Hemoglobin < 9 g/dL
- White blood cell (WBC) count < 3000 /μL (≥ 3.0 X 109/L) and ≥ 14,000/μL (≥ 20 X
- Neutrophils < 1500 /μL (< 1.5 X 109/L)
- Platelets < 100,000 /μL (< 100 X 109/L)
- Serum creatinine > 1.5 mg/dL (> 132.6 μmol/L)
- Total bilirubin > 2.0 mg/dL
- Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and
alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) > 1.5x upper
limit of normal (ULN)