A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN THE TREATMENT OF ACTIVE ANKYLOSING SPONDYLITIS

Phase 3

Completed

• Conditions: Bekhterev's disease; Chronic inflammatory disease of the axial skeleton; 10023213

• Registration Number: NL-OMON37830
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2019-06-17
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

1. Must have a documented diagnosis of ankylosing spondylitis as defined by low back pain and stiffness, which improves with exercise, but is not relieved by rest for more than
3 months prior to screening. At the completion of screening procedures, a documented diagnosis of definite active AS, as defined by the modified New York criteria (1984) whereby both criteria, at least 1 radiographic criterion and at least 1 clinical criterion, must be met (Appendix A of the protocol):
a. Radiographic criteria (at least 1), documented by the central reader before the subject is randomized:
i. Sacroiliitis Grade >= 2 bilaterally, or
ii. Sacroiliitis Grade 3 to 4 unilaterally
b. Clinical criteria (at least 1), documented in physical examination:
i. Low back pain and stiffness for more than 3 months, which improves with exercise, but is not relieved by rest
ii. Limitation of motion of the lumbar spine in both the sagittal and frontal planes
iii. Limitation of chest expansion relative to normal values corrected for age and gender
2. Must have symptoms of active axial disease at screening and baseline (at time of randomization), as determined by a BASDAI NRS score of >= 4 and a total back pain NRS score >= 4.
3. Must be receiving treatment on an outpatient basis.
4. Must be in good health (except for AS) as judged by the Investigator, based on medical history, physical examination, 12-lead ECG, chest radiograph, clinical laboratories and urinalysis.
5.,Must agree to maintain the same stable dose of medication (or lack of medication) taken for AS prior to randomization through Week 24 of the study as described below. Change in medication may be allowed for safety reasons (See Section 9.1 of the protocol).
a. Analgesics must be stable for at least 14 days prior to Day 0
i. Non-investigational NSAIDs and/or COX-2 inhibitors
ii. Acetaminophen/paracetamol <= 2600 mg/day
iii. Opioid analgesics <= 30 mg oral morphine or equivalent per day
b. Disease-modifying anti-rheumatic drugs (DMARDs) must have been taken for at least 16 weeks and must be stable for at least 28 days prior to Day 0 within the following doses:
i. Methotrexate: oral <= 25 mg/week; parenteral <= 25 mg/week
Note: Supplemental oral folate (folic acid) is required with a minimum dose of 5 mg/week, or oral leucovorin up to 10 mg/week for subjects taking methotrexate).
ii. Sulfasalazine <= 3 g/day
iii. Hydroxychloroquine <= 400 mg/day; Chloroquine <= 250 mg/day
Note: Regular safety monitoring, particularly eye exams must be conducted according to local practice guideline for subjects on hydroxychloroquine or chloroquine.
c. Corticosteroids (prednisone <= 10 mg/day or prednisone-equivalent) must be stable for at least 28 days prior to Day 0.
6. Must meet the following laboratory criteria at screening:
a. White blood cell count >= 3000/mm3 (>= 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L)
b. Platelet count >= 100,000/µL (>= 100 x 109/L)
c. Serum creatinine <= 1.5 mg/dL (<= 132.6 µmol/L)
d. AST (SGOT) and ALT (SGPT) <= 2 x upper limit of normal (ULN). If initial test shows ALT or AST > 2 times the ULN, one repeat test is allowed during the screening period.
e. Total bilirubin <= 2 mg/dL (<= 34 µmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the screening period.
f. Hemoglobin >= 9 g/dL (>= 5.6 mmol/L)
g. Hemoglobin A1c <= 9.0%
h. Negative f

Exclusion Criteria

1. Major surgery (including spinal surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
2. Autoimmune diseases such as, but not limited to: systemic lupus erythematosus, mixed connective tissue disease, multiple sclerosis, or scleroderma.
3. Prior history of, or current, inflammatory joint disease other than AS (eg, rheumatoid arthritis, gout, reactive arthritis, psoriatic arthritis, Lyme disease).
4. Uncontrolled, severe psoriasis (defined as Body Surface Area > 10%) or active inflammatory bowel disease (Crohn*s disease or ulcerative colitis) based on an unequivocal positive calprotectin stool test defined by the local or central lab reference values.
5. Uncontrolled uveitis at the time of randomization. Asymptomatic, concurrently treated and controlled uveitis is acceptable at randomization, as long as the treatment is limited to topical ophthalmic therapy and/or intra-ocular injections of corticosteroids. Subjects are allowed to be initiated with these therapies during screening, continue on them through randomization and tapered off or discontinue these therapies while on study as medically appropriate. Systemic treatment for uveitis is not allowed, and would result in discontinuation from the study.
6. Prior treatment with a TNF blocker or any biologic treatment for AS.
7. If discontinuing treatment of DMARD, then adequate washout is required prior to randomization (See separate sheet of List of DMARD Washout Periods).
8. Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
9. Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
10. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint will be the proportion of subjects who achieve an ASAS 20<br /><br>at Week 16. The ASAS is the Assessment of SpondyloArthritis international<br /><br>Society (see Section 10.1.1 for ASAS response definitions). The ASAS 20 is<br /><br>defined as achieving:<br /><br>• An improvement from baseline of >= 20% and >= 1 unit in at least three of the<br /><br>four ASAS domains on a scale of 0 to 10 units, and<br /><br>• No worsening from baseline of >= 20% and >= 1 unit in the remaining ASAS domain<br /><br>on a scale of 0 to 10 units.<br /><br>The four ASAS domains are:<br /><br>1. Patient Global Assessment of Disease (0 to 10 unit NRS);<br /><br>2. Total Back Pain NRS;<br /><br>3. Function (the Bath Ankylosing Spondylitis Functional Index [BASFI] score<br /><br>NRS);<br /><br>4. Inflammation (mean of the two Bath Ankylosing Spondylitis Disease Activity<br /><br>Index [BASDAI] NRS Questions #5 and #6 for morning stiffness).</p><br>