Spondylitis Trial of Apremilast for Better Rheumatic Therapy
Condition: Ankylosing Spondylitis
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
Intervention: Apremilast; Placebo (sugar pill)
Intervention description: 10mg twice a day, dose was titrated by 20mg every 2 days until the maximum dose 30mg twice a day for 12weeks; twice a day
Intervention MeSH terms: Apremilast
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ankylosing spondylitis; Imaging

Summary:

      This study will evaluate the effectiveness of apremilast in AS as measured by improvement in
      patients' signs and symptoms of the disease and changes in imaging. Additionally the safety
      and tolerability of apremilast in AS will be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 planes;

               3. limited chest expansion, relative to standard values for age and sex;

               4. definite radiographic / imaging evidence of sacroiliitis and/or spinal
                  inflammation

          -  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.

        Exclusion Criteria:

          -  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
                  ELISPOT positive

          -  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
             (Appendix H)

          -  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 .

          -  Claustrophobia

          -  Hemoglobin < 9 g/dL

          -  White blood cell (WBC) count < 3000 /μL (≥ 3.0 X 109/L) and ≥ 14,000/μL (≥ 20 X 109/L)

          -  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)