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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.
 
ClinicalTrials.gov Identifier: NCT00944658
Recruitment Status : Completed
First Posted : July 23, 2009
Results First Posted : December 6, 2019
Last Update Posted : December 6, 2019
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Imperial College London

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 tolerability of apremilast in AS will be assessed.

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

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). 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.

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.

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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)
Actual Study Start Date : August 2009
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Apremilast

Arm Intervention/treatment
Placebo Comparator: Placebo
placebo twice a day for 12 weeks, 4 weeks follow up
Drug: Placebo (sugar pill)
twice a day

Active Comparator: Apremilast
30 mg twice a day for 12 weeks, 4 weeks follow up
Drug: Apremilast
10mg twice a day, dose was titrated by 20mg every 2 days until the maximum dose 30mg twice a day for 12weeks




Primary Outcome Measures :
  1. Changes of Apremilast in Patients With AS, Changes in BASDAI Score From Baseline [ Time Frame: Baseline and 12 weeks ]
    Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease.

  2. Changes of Apremilast on the Signs and Symptoms of AS, Night Pain From Baseline [ Time Frame: Baseline and 12 weeks ]

    This endpoint the night time pain score change was recorded by questionnaire to evaluate the Apremilast effect on symptom, higher reduction better improvement.

    scale is 0-10


  3. Effect of Apremilast in Patients With AS, Changes in BASFI Score [ Time Frame: Baseline and 12 weeks ]
    Bath Ankylosing Spondylitis Functional Index (BASFI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease.


Secondary Outcome Measures :
  1. The Safety and Tolerability of Apremilast in AS, Number of Participants With Adverse Events [ Time Frame: 16 weeks ]
    To evaluate the safety and tolerability of Apremilast in AS, the investigator recorded the incidence of adverse events.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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 ClinicalTrials.gov identifier (NCT number): NCT00944658


Locations
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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
Investigators
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Principal Investigator: Peter Taylor Imperial College London
Publications of Results:
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00944658    
Other Study ID Numbers: 112008
2008-004229-40 ( EudraCT Number )
First Posted: July 23, 2009    Key Record Dates
Results First Posted: December 6, 2019
Last Update Posted: December 6, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Ankylosing spondylitis
Imaging
Additional relevant MeSH terms:
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Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
Apremilast
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents