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A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease

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ClinicalTrials.gov Identifier: NCT00866359
Recruitment Status : Completed
First Posted : March 20, 2009
Results First Posted : August 27, 2014
Last Update Posted : November 17, 2017
Sponsor:
Information provided by (Responsible Party):
Celgene

March 18, 2009
March 20, 2009
April 22, 2014
August 27, 2014
November 17, 2017
August 1, 2009
May 1, 2012   (Final data collection date for primary outcome measure)
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).
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.
Complete list of historical versions of study NCT00866359 on ClinicalTrials.gov Archive Site
  • 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 ]
    A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:
    1. Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);
    2. 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;
    3. Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;
    4. 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'
    5. 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 [ 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).
  • 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.
  • 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.
  • 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.
  • 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:
    1. Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);
    2. 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;
    3. Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;
    4. 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;
    5. 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 [ 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).
  • 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.
  • 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.
  • 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.
  • 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.
Painoforal/genitalulcersmeasuredbyVAS,AUC&Sumoforal/genitalulcers,#ofulcer freesubjects&thosewith>=50%reduction,BDCAForm score, SafetyAssessments,NewBDmanifestations,PtReportedOutcomes questionnaires,Systemic&populationPKAssessments
  • 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)
  • 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)
  • 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)
Not Provided
 
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
The purpose of this study is to assess whether Apremilast is safe and effective in the treatment of patients with Behcet Disease.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Behcet Syndrome
  • Drug: Apremilast (CC-10004)

    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)

  • Drug: Placebo

    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)

  • Active Comparator: A. Apremilast
    Intervention: Drug: Apremilast (CC-10004)
  • Placebo Comparator: B. Placebo Comparator
    Intervention: Drug: Placebo
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 Behçet's syndrome--a phase 2, placebo-controlled study. N Engl J Med. 2015 Apr 16;372(16):1510-8. doi: 10.1056/NEJMoa1408684.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
111
156
May 1, 2012
May 1, 2012   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Turkey,   United States
 
 
NCT00866359
CC-10004-BCT-001
EudraCT#: 2008-002722-11
Yes
Not Provided
Not Provided
Celgene
Celgene
Not Provided
Principal Investigator: Yusuf Yazici, MD NYU Hospital for Joint Diseases
Celgene
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP