Clinical Trial: A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
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
Brief Summary: The purpose of this study is to assess whether Apremilast is safe and effective in the treatment of patients with Behcet Disease.
Detailed Summary:
This is a phase 2, multi-center, randomized, placebo-controlled, double-blind, parallel-group study with an equal randomization between the apremilast and placebo treatment groups. Following the randomized Treatment Phase, each participant will enter an active-treatment Extension Phase.
The study will consist of four phases: a Pre-randomization Phase, a Treatment Phase, an Extension Phase, and an Observational Follow-up Phase.
Pre-randomization Phase Screening procedures must be performed no more than 90 days prior to the start of study medication at Visit 2 (Day 1).
Treatment Phase Participants who qualify for randomization will be randomized 1:1 to receive study medication (apremilast) or placebo. Since the incidence and severity of Behçet Disease differ between males and females, randomization will be stratified by gender, to minimize the imbalance between the two treatment groups.
To mitigate the potential gastrointestinal (GI) side effects of apremilast (primarily mild-to-moderate nausea), dose titration for the first week of treatment will be implemented for this study. Participants will be dosed orally twice per day (PO BID) with 10 mg apremilast or identically-appearing placebo on Days 1 and 2, followed by 20 mg BID or placebo on Days 3 and 4, and by 30 mg BID or placebo on Days 5-7. Thereafter, participants will take 30 mg BID of apremilast or matching placebo through Day 85.
If participants are unable to tolerate the adverse events of the full dose of study medication, they may be permitted to take a reduced dose of 20 mg BID of apremilast after the investigator consults with the study sponsor. Participants who are dose reduced while on placebo medication will
Sponsor: Celgene Corporation
Current Primary Outcome: Number of Oral Ulcers at Day 85 [ Time Frame: Day 85 ]
Original Primary Outcome: The change in the number of oral ulcers from Baseline to Day 85/Early Termination will be compared between the Apremilast and the placebo treatment groups.
Current Secondary Outcome:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- Number of New Manifestations of Behçet's Disease or Flare During the Placebo Controlled Treatment Phase [ Time Frame: Day 1 to Day 85 ]
Original Secondary Outcome: Painoforal/genitalulcersmeasuredbyVAS,AUC&Sumoforal/genitalulcers,#ofulcer freesubjects&thosewith>=50%reduction,BDCAForm score, SafetyAssessments,NewBDmanifestations,PtReportedOutcomes questionnaires,Systemic&populationPKAssessments
Information By: Celgene Corporation
Dates:
Date Received: March 18, 2009
Date Started: October 2009
Date Completion:
Last Updated: June 14, 2016
Last Verified: June 2016
