Spondylitis Trial of Apremilast for Better Rheumatic Therapy (START)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00944658
Recruitment Status : Completed
First Posted : July 23, 2009
Last Update Posted : September 30, 2011
Celgene Corporation
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

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). However, there are limitations with this treatment in that it needs to be administered via an injection and is also very expensive. Therefore it is necessary to develop new therapeutic agents for this condition.

Apremilast (the study drug) is an oral tablet which has been shown to inhibit TNF production in a mouse model of inflammation. It has also been used in clinical trials for asthma and psoriasis in humans with good affect and tolerability.

These studies were funded by Celgene Corporation and they will be funding this study.

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. The patients will be recruited from hospitals by Consultant referral. The patients will have had AS for at least 2 years and their symptoms will have been uncontrolled on conventional non−steroidal anti−inflammatory drugs such as ibuprofen. Patients will be randomised to either receive apremilast or a placebo and treated over a period of 12 weeks. They will then be followed up for 28 days after the treatment period.

Condition or disease Intervention/treatment Phase
Ankylosing Spondylitis Drug: Apremilast Drug: Placebo (sugar pill) Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : August 2009
Primary Completion Date : January 2011
Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Apremilast
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Apremilast Drug: Apremilast
As per protocol
Other Name: As per protocol
Placebo Comparator: Sugar pill Drug: Placebo (sugar pill)
As per protocol

Primary Outcome Measures :
  1. To demonstrate the effect of apremilast on MRI lesions in AS [ Time Frame: 3 months ]
  2. To explore the effect of apremilast on the signs and symptoms of AS [ Time Frame: 4 months ]

Secondary Outcome Measures :
  1. To explore the safety and tolerability of apremilast in AS [ Time Frame: Day 1 - day 113 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00944658

United Kingdom
The Kennedy Institute Clinical Trials Unit, 4 West, Charing Cross Hospital
London, United Kingdom, W6 8RF
Sponsors and Collaborators
Imperial College London
Celgene Corporation
Principal Investigator: Peter Taylor Imperial College London

Responsible Party: Imperial College London Identifier: NCT00944658     History of Changes
Other Study ID Numbers: 112008
EUdraCT No 2008-004229-40
First Posted: July 23, 2009    Key Record Dates
Last Update Posted: September 30, 2011
Last Verified: September 2011

Keywords provided by Imperial College London:
Ankylosing spondylitis

Additional relevant MeSH terms:
Spondylitis, Ankylosing
Bone Diseases, Infectious
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Joint Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances