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) - START - Spondylitis Trial of Apremilast for better Rheumatic Therapy

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-004229-40-GB
• Date of registration: 22/11/2010
• Prospective Registration: No
• Primary sponsor: Imperial College London
• Public 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) - START - Spondylitis Trial of Apremilast for better Rheumatic Therapy
• Scientific 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) - START - Spondylitis Trial of Apremilast for better Rheumatic Therapy
• Date of first enrolment: 09/03/2009
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004229-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
a) Written informed consent to participate in this trial

b) 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

c) 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.

d) Patients receiving NSAIDS and/or COX-2 inhibitors must be on stable doses for at least 2 weeks prior to randomization.

e) Age >18 years.

f) 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.

g) Women of childbearing potential, not surgically sterile or postmenopausal, must have a negative serum beta HCG.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
a) Use of DMARDs (methotrexate, d-penicillamine, sulfasalazine, azathioprine,
hydroxychloroquine, or gold) within 8 weeks of randomization.

b) Use of systemic corticosteroids within 4 weeks of randomization.

c) Use of intravenous or intra-articular corticosteroids within 4 weeks of randomization.

d) Use of TNF alpha blockers eg, infliximab (within 12 weeks), adalimumab (within 10 weeks) or etanercept (within 4 weeks).

e) Therapy with an investigational agent within 30 days of randomization or 5 half-lives (pharmacokinetic or pharmacodynamic), which ever is longer.

f) Known HIV or hepatitis B or C infection.

g) 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 is greater than 5 mm or ELISPOT positive.

h) History of other rheumatic autoimmune diseases (eg, systemic lupus erythematosus, rheumatoid arthritis, etc.)

i) Pregnant or nursing women

j) Any condition, in the investigator's opinion, which places the patient at an undue risk by participating in the study.

k) Contraindication to MRI and other MRI exclusions following local centre guidelines (Appendix H)

l) An estimated glomerular filtration rate (eGFR) of < 60 ml/min (because of the small risk of nephrogenic sclerosing.

fibrosis with gadolinium intravenous contrast).

m) Claustrophobia.

n) Hemoglobin < 9 g/dL.

o) White blood cell (WBC) count < 3000 /µL ( 3.0 X 109/L) and 14,000/µL ( 20 X 109/L).

p) Neutrophils < 1500 /µL (< 1.5 X 109/L).

q) Platelets < 100,000 /µL (< 100 X 109/L).

r) Serum creatinine > 1.5 mg/dL (> 132.6 µmol/L).

s) Total bilirubin > 2.0 mg/dL.

t) Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT
[serum glutamate pyruvic transaminase, SGPT]) > 1.5x upper limit of normal (ULN).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ankylosing Spondylitis
MedDRA version: 9.1 Level: LLT Classification code 10002556 Term: Ankylosing spondylitis

Intervention(s)

Product Name: Apremilast
Product Code: CC-10004
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Apremilast
CAS Number: 608141-41-9
Current Sponsor code: CC-10004
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20 twice a day-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Apremilast
Product Code: CC-10004
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Apremilast
CAS Number: 608141-41-9
Current Sponsor code: CC-10004
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10 twice a day-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To demonstrate the effect of apremilast on magnetic resonance imaging lesions in ankylosing spondylitis.

To explore the effect of apremilast on the signs and symptoms of ankylosing spondylitis.

Primary end point(s): To investigate changes in MRI of the spine and sacro-iliac joints pre and post apremilast compared to placebo and to examine the effects on signs and symptoms of the disease.

Secondary Objective: To explore the safety and tolerability of apremilast in ankylosing spondylitis.

Secondary ID(s)

112008