Spondylitis Trial of Apremilast for Better Rheumatic Therapy (START)

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT00944658
First received: July 20, 2009
Last updated: September 29, 2011
Last verified: September 2011
  Purpose

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 Intervention Phase
Ankylosing Spondylitis
Drug: Apremilast
Drug: Placebo (sugar pill)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • To demonstrate the effect of apremilast on MRI lesions in AS [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • To explore the effect of apremilast on the signs and symptoms of AS [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To explore the safety and tolerability of apremilast in AS [ Time Frame: Day 1 - day 113 ] [ Designated as safety issue: Yes ]

Enrollment: 38
Study Start Date: August 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Apremilast Drug: Apremilast
As per protocol
Other Name: As per protocol
Placebo Comparator: Sugar pill Drug: Placebo (sugar pill)
As per protocol

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00944658

Locations
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
Principal Investigator: Peter Taylor Imperial College London
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00944658     History of Changes
Other Study ID Numbers: 112008, EUdraCT No 2008-004229-40
Study First Received: July 20, 2009
Last Updated: September 29, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Ankylosing spondylitis
Imaging

Additional relevant MeSH terms:
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
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 19, 2014