- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00866359
A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Followed by an Active-Treatment Extension to Evaluate the Efficacy and Safety of Apremilast(CC-10004) in the Treatment of Behçet Disease
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
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Eskişehir, Turkey, 26480
- Eskisehir Osmangazi University
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Istanbul, Turkey, 34098
- University of Istanbul
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Konya, Turkey, 42080
- Selcuk University
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-
-
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic - Rheumatology and Internal Medicine
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Massachusetts
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Boston, Massachusetts, United States, 02118
- E5, Boston University School of Medicine
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New York
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New York, New York, United States, 10003
- NYU Hospital for Joint Diseases
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of Behçet Disease. At the time of diagnosis, subjects must meet the international study group criteria for Behçet Disease
- Females of childbearing potential (FCBP) must have negative pregnancy tests and agree to use two forms of contraception throughout the study.
- Males must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP
- Laboratory criteria: Hgb ≥ 9 g/dL, WBC count ≥ 3000 /microL and ≤14,000/microL, platelet count ≥ 100,000 /microL,, serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L), total bilirubin ≤ 2.0 mg/dL, AST and ALT ≤ 1.5 X ULN
- Two or more oral ulcers over the 28 day period before screening, with or without current treatment
- Two or more oral ulcers at the time of randomization (Visit 2, Baseline)
Exclusion Criteria:
- Pregnant or breast feeding
- Any condition which places the subject at risk
- Systemic fungal infection
- History of TB infection within 3 years
- History of recurrent bacterial infection
- Mycobacterium TB as indicated by a positive PPD skin test
- History of incompletely treated Mycobacterium tuberculosis
- Clinically significant chest x-ray abnormality at screening.
- Clinically significant ECG abnormality at screening
- History of HIV infection
- History of congenital or acquired immunodeficiency
- Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening
- Antibodies to Hepatitis C at screening
- History of malignancy (except for treated basal-cell skin carcinomas > 3 years prior to screening)
- Any active major organ involvement of Behçet Disease
- Use of concomitant immune modulating therapy or topical corticosteroids.
- Use of ocular corticosteroids
- Use of any investigational medication within 4 weeks prior to randomization or 5 PK/PD half-lives (whichever is longer)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: A. Apremilast
|
Treatment Phase Days 1-7: Titration from 10 mg BID apremilast tablets arm A (or matching placebo arm B) to 30 mg BID apremilast arm A(or matching placebo arm B) Day 8-84: Maintenance of 30 mg BID apremilast arm A (or matching placebo arm B) Dose reductions to 20 mg BID apremilast arm A (or matching placebo arm B) are permitted. Extension Phase All subjects will be given active drug Days 85-91: All placebo subjects from Treatment phase will be dose titrated from 10 mg BID apremilast tablets arm A to 30 mg BID Apremilast. Day 92-169: Maintenance of 30 mg BID apremilast arm A or dose reductions to 20 mg BID apremilast arm A (if not previously down titrated) |
Placebo Comparator: B. Placebo Comparator
|
Treatment Phase Days 1-7: Titration from 10mg BID matching placebo (arm B) to 30mg BID placebo (arm B) Day 8-84: Maintenance of 30mg BID placebo (arm B). Dose reductions to 20 mg BID matching placebo (arm B) are permitted. Extension Phase All subjects will be given active drug Days 85-91: All placebo subjects from Treatment phase will be dose titrated from 10 mg BID apremilast tablets arm A to 30 mg BID Apremilast. Day 92-169: Maintenance of 30 mg BID apremilast or dose reductions to 20 mg BID apremilast (if not previously down titrated) |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Oral Ulcers at Day 85
Time Frame: Day 85
|
The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).
|
Day 85
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pain of Oral Ulcers as Measured by Visual Analog Scale (VAS) at Day 85
Time Frame: Day 85
|
A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol.
Each 100-mm VAS was presented to the participant on a single sheet of bond paper.
The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable.
The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded.
When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.
|
Day 85
|
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) Scores at Day 85
Time Frame: Baseline to Day 85
|
A 100-mm VAS pain scale for genital ulcers was completed by the participant at timepoints specified in the protocol.
Each 100-mm VAS was presented to the participant on a single sheet of bond paper.
The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable.
The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded.
When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.
|
Baseline to Day 85
|
Area Under the Curve (AUC) for the Number of Oral Ulcers From Day 1 to 85
Time Frame: Day 1 to Day 85
|
Area under curve (AUC^85) from Day 1 to Day 85 for the number of oral ulcers per day was determined using the trapezoidal rule and divided by the days between the date of the last observation and baseline.
The AUC was determined using the LOCF approach to impute missing values.
|
Day 1 to Day 85
|
Area Under the Curve for the Number of Genital Ulcers From Day 1 to 85
Time Frame: Day 1 to Day 85
|
Area under curve (AUC^85) from Day 1 to Day 85 for the number of genital ulcers per day was not analyzed.
|
Day 1 to Day 85
|
Area Under the Curve (AUC) for the Number of Oral Plus Genital Ulcers From Day 1 to 85
Time Frame: Day 1 to Day 85
|
Area under curve (AUC) from Day 1 to Day 85 (AUC^85) for the number of oral plus genital ulcers per day was determined using the trapezoidal rule and divided by the days between the date of the last observation and baseline.
The AUC was determined using the LOCF approach to impute missing values.
|
Day 1 to Day 85
|
Sum of the Number Oral Ulcers, Genital Ulcers or Oral Plus Genital Ulcers at Day 85
Time Frame: Day 85
|
Sum of the number oral ulcers, genital ulcers or oral plus genital ulcers at Day 85
|
Day 85
|
Percentage of Participants Who Were Oral Ulcer-free (Complete Response), or Whose Oral Ulcers Were Reduced by ≥ 50%, (Partial Response)
Time Frame: Baseline and Day 85
|
Comparison of the percentage of participants who were oral ulcer-free (complete response: free from active oral ulcers), or whose oral ulcers were reduced by ≥ 50%, (partial response) between the apremilast-treated and the placebo-treated groups.
In this case, partial response also includes complete response.
|
Baseline and Day 85
|
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 85
Time Frame: Day 1 to Day 85 or to early termination visit
|
The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score.
The score ranges from 0 to 12.
A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement.
|
Day 1 to Day 85 or to early termination visit
|
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase
Time Frame: Day 1 to Day 85; maximum exposure to study drug was 13 weeks during treatment phase
|
A Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring or worsening on or after the first treatment of any study drug, and within 28 days after the last dose of the last study drug.
A treatment related toxicity was considered by the investigator to be not suspected or suspected.
Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE.
|
Day 1 to Day 85; maximum exposure to study drug was 13 weeks during treatment phase
|
Number of New Manifestations of Behçet's Disease or Flare During the Placebo Controlled Treatment Phase
Time Frame: Day 1 to Day 85
|
A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:
|
Day 1 to Day 85
|
Number of Oral Ulcers at Day 169
Time Frame: Day 169
|
The number of oral ulcers were counted at Day 169 in reference to the participants' first day of active treatment (Day 1 or Day 85).
|
Day 169
|
Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 169
Time Frame: Day 169
|
A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol.
Each 100-mm VAS was presented to the participant on a single sheet of bond paper.
The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable.
The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded.
When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.
|
Day 169
|
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at Day 169
Time Frame: Day 1 to Day 169
|
A 100-mm VAS pain scale for genital ulcers was completed by the participant at timepoints specified in the protocol.
Each 100-mm VAS was presented to the participant on a single sheet of bond paper.
The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable.
The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded.
When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.
|
Day 1 to Day 169
|
Behçet's Disease (BD) Current Activity Index Form Score at Day 169
Time Frame: Day 169
|
The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score.
The score ranges from 0 to 12.
A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement.
|
Day 169
|
Number of New Manifestations of Behçet's Disease or Flare That Were Not Present at Day 1
Time Frame: Day 1 to Day 169
|
A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:
|
Day 1 to Day 169
|
Number of Oral Ulcers at Day 197
Time Frame: Day 197
|
The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).
|
Day 197
|
Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 197
Time Frame: Day 197
|
A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol.
Each 100-mm VAS was presented to the participant on a single sheet of bond paper.
The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable.
The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded.
When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.
|
Day 197
|
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at Day 197
Time Frame: Day 1 to Day 197
|
A 100-mm VAS pain scale for genital ulcers was completed by the participant at timepoints specified in the protocol.
Each 100-mm VAS was presented to the participant on a single sheet of bond paper.
The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable.
The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded.
When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.
|
Day 1 to Day 197
|
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 197
Time Frame: Day 1 to Day 197
|
The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score.
The score ranges from 0 to 12.
A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement.
|
Day 1 to Day 197
|
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase
Time Frame: Day 1 to Day 197; maximum exposure was 25.1 weeks
|
A Treatment Emergent Adverse Event (TEAE) is as any AE occurring or worsening on or after the first treatment of any study drug, and within 28 days after the last dose of the last study drug.
A treatment related toxicity was considered by the investigator to be not suspected or suspected.
Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE.
|
Day 1 to Day 197; maximum exposure was 25.1 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 85
Time Frame: Baseline to Day 85
|
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)
|
Baseline to Day 85
|
Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 169
Time Frame: Day 1 to Day 169
|
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)
|
Day 1 to Day 169
|
Percentage of Participants Who Were Genital Ulcer-free (Complete Response)
Time Frame: Day 1 to Day 197
|
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)
|
Day 1 to Day 197
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Skin Diseases
- Eye Diseases
- Genetic Diseases, Inborn
- Stomatognathic Diseases
- Mouth Diseases
- Uveitis, Anterior
- Panuveitis
- Uveitis
- Uveal Diseases
- Vasculitis
- Hereditary Autoinflammatory Diseases
- Skin Diseases, Genetic
- Skin Diseases, Vascular
- Behcet Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Phosphodiesterase Inhibitors
- Phosphodiesterase 4 Inhibitors
- Apremilast
Other Study ID Numbers
- CC-10004-BCT-001
- EudraCT#: 2008-002722-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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