Status:

COMPLETED

Spondylitis Trial of Apremilast for Better Rheumatic Therapy

Lead Sponsor:

Imperial College London

Collaborating Sponsors:

Celgene Corporation

Conditions:

Ankylosing Spondylitis

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief 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 tolerabilit...

Detailed Description

Presently, there are very few treatments available which affect the progression of the disease in the spine. The only proven treatment is the use of drugs inhibiting tumour necrosis factor alpha (TNF)...

Eligibility Criteria

Inclusion

  • Written informed consent to participate in this trial
  • Diagnosis of ankylosing spondylitis as defined by the modified New York criteria (1984) as follows:
  • a history of inflammatory back pain;
  • limitation of motion of the lumbar spine in both the sagittal and frontal planes;
  • limited chest expansion, relative to standard values for age and sex;
  • 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

  • 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)

Key Trial Info

Start Date :

August 1 2009

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 1 2011

Estimated Enrollment :

38 Patients enrolled

Trial Details

Trial ID

NCT00944658

Start Date

August 1 2009

End Date

January 1 2011

Last Update

December 6 2019

Active Locations (1)

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1

The Kennedy Institute Clinical Trials Unit, 4 West, Charing Cross Hospital

London, United Kingdom, W6 8RF