Back to resultsA Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
Primary Purpose
Behcet Syndrome
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Apremilast (CC-10004)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Behcet Syndrome
Eligibility Criteria
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)
Sites / Locations
- Mayo Clinic - Rheumatology and Internal Medicine
- E5, Boston University School of Medicine
- NYU Hospital for Joint Diseases
- Cleveland Clinic Foundation
- Eskişehir Osmangazi University
- University of Istanbul
- Selçuk University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
A. Apremilast
B. Placebo Comparator
Arm Description
Outcomes
Primary Outcome Measures
Number of Oral Ulcers at 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).
Secondary Outcome Measures
Pain of Oral Ulcers as Measured by Visual Analog Scale (VAS) at 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.
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) Scores at 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.
Area Under the Curve (AUC) for the Number of Oral Ulcers From Day 1 to 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.
Area Under the Curve for the Number of Genital Ulcers From Day 1 to 85
Area under curve (AUC^85) from Day 1 to Day 85 for the number of genital ulcers per day was not analyzed.
Area Under the Curve (AUC) for the Number of Oral Plus Genital Ulcers From Day 1 to 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.
Sum of the Number Oral Ulcers, Genital Ulcers or Oral Plus Genital Ulcers at Day 85
Sum of the number oral ulcers, genital ulcers or oral plus genital ulcers at Day 85
Percentage of Participants Who Were Oral Ulcer-free (Complete Response), or Whose Oral Ulcers Were Reduced by ≥ 50%, (Partial Response)
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.
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 85
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.
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled 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.
Number of New Manifestations of Behçet's Disease or Flare During the Placebo Controlled Treatment Phase
A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:
Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);
Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;
Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;
Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater'
New onset or worsening of existing Behçet Disease-related inflammatory eye disease requiring initiation of immunosuppressive therapy (uveitis).
Number of Oral Ulcers at 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).
Pain of Oral Ulcers as Measured by VAS (VAS Score) at 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.
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at 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.
Behçet's Disease (BD) Current Activity Index Form Score at 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.
Number of New Manifestations of Behçet's Disease or Flare That Were Not Present at Day 1
A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:
Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);
Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;
Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;
Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater;
New onset or worsening of existing Behçet Disease-related inflammatory eye disease requiring initiation of immunosuppressive therapy (uveitis).
Number of Oral Ulcers at 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).
Pain of Oral Ulcers as Measured by VAS (VAS Score) at 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.
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at 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.
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on 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.
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00866359
Brief Title
A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
August 1, 2009 (Actual)
Primary Completion Date
May 1, 2012 (Actual)
Study Completion Date
May 1, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess whether Apremilast is safe and effective in the treatment of patients with Behcet Disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Behcet Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
111 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A. Apremilast
Arm Type
Active Comparator
Arm Title
B. Placebo Comparator
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Apremilast (CC-10004)
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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)
Primary Outcome Measure Information:
Title
Number of Oral Ulcers at Day 85
Description
The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).
Time Frame
Day 85
Secondary Outcome Measure Information:
Title
Pain of Oral Ulcers as Measured by Visual Analog Scale (VAS) at Day 85
Description
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.
Time Frame
Day 85
Title
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) Scores at Day 85
Description
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.
Time Frame
Baseline to Day 85
Title
Area Under the Curve (AUC) for the Number of Oral Ulcers From Day 1 to 85
Description
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.
Time Frame
Day 1 to Day 85
Title
Area Under the Curve for the Number of Genital Ulcers From Day 1 to 85
Description
Area under curve (AUC^85) from Day 1 to Day 85 for the number of genital ulcers per day was not analyzed.
Time Frame
Day 1 to Day 85
Title
Area Under the Curve (AUC) for the Number of Oral Plus Genital Ulcers From Day 1 to 85
Description
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.
Time Frame
Day 1 to Day 85
Title
Sum of the Number Oral Ulcers, Genital Ulcers or Oral Plus Genital Ulcers at Day 85
Description
Sum of the number oral ulcers, genital ulcers or oral plus genital ulcers at Day 85
Time Frame
Day 85
Title
Percentage of Participants Who Were Oral Ulcer-free (Complete Response), or Whose Oral Ulcers Were Reduced by ≥ 50%, (Partial Response)
Description
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.
Time Frame
Baseline and Day 85
Title
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 85
Description
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.
Time Frame
Day 1 to Day 85 or to early termination visit
Title
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase
Description
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.
Time Frame
Day 1 to Day 85; maximum exposure to study drug was 13 weeks during treatment phase
Title
Number of New Manifestations of Behçet's Disease or Flare During the Placebo Controlled Treatment Phase
Description
A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:
Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);
Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;
Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;
Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater'
New onset or worsening of existing Behçet Disease-related inflammatory eye disease requiring initiation of immunosuppressive therapy (uveitis).
Time Frame
Day 1 to Day 85
Title
Number of Oral Ulcers at Day 169
Description
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).
Time Frame
Day 169
Title
Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 169
Description
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.
Time Frame
Day 169
Title
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at Day 169
Description
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.
Time Frame
Day 1 to Day 169
Title
Behçet's Disease (BD) Current Activity Index Form Score at Day 169
Description
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.
Time Frame
Day 169
Title
Number of New Manifestations of Behçet's Disease or Flare That Were Not Present at Day 1
Description
A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:
Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);
Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;
Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;
Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater;
New onset or worsening of existing Behçet Disease-related inflammatory eye disease requiring initiation of immunosuppressive therapy (uveitis).
Time Frame
Day 1 to Day 169
Title
Number of Oral Ulcers at Day 197
Description
The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).
Time Frame
Day 197
Title
Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 197
Description
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.
Time Frame
Day 197
Title
Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at Day 197
Description
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.
Time Frame
Day 1 to Day 197
Title
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 197
Description
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.
Time Frame
Day 1 to Day 197
Title
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase
Description
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.
Time Frame
Day 1 to Day 197; maximum exposure was 25.1 weeks
Other Pre-specified Outcome Measures:
Title
Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 85
Description
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)
Time Frame
Baseline to Day 85
Title
Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 169
Description
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)
Time Frame
Day 1 to Day 169
Title
Percentage of Participants Who Were Genital Ulcer-free (Complete Response)
Description
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)
Time Frame
Day 1 to Day 197
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic - Rheumatology and Internal Medicine
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
E5, Boston University School of Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
NYU Hospital for Joint Diseases
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Eskişehir Osmangazi University
City
Eskişehir
ZIP/Postal Code
26480
Country
Turkey
Facility Name
University of Istanbul
City
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Selçuk University
City
Konya
ZIP/Postal Code
42080
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
IPD Sharing Time Frame
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
IPD Sharing Access Criteria
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
IPD Sharing URL
http://www.amgen.com/datasharing
Citations:
PubMed Identifier
25875256
Citation
Hatemi G, Melikoglu M, Tunc R, Korkmaz C, Turgut Ozturk B, Mat C, Merkel PA, Calamia KT, Liu Z, Pineda L, Stevens RM, Yazici H, Yazici Y. Apremilast for Behcet's syndrome--a phase 2, placebo-controlled study. N Engl J Med. 2015 Apr 16;372(16):1510-8. doi: 10.1056/NEJMoa1408684.
Results Reference
derived
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
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