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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00866359
First received: March 18, 2009
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to assess whether Apremilast is safe and effective in the treatment of patients with Behcet Disease.


Condition Intervention Phase
Behcet Syndrome
Drug: Apremilast (CC-10004)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Number of Oral Ulcers at Day 85 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 85 [ Time Frame: Baseline to Day 85 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)


Enrollment: 111
Study Start Date: October 2009
Study Completion Date: July 2013
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A. Apremilast 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 8-85: 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 86-91: 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)

Other Name: Otezla
Placebo Comparator: B. Placebo Comparator 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)


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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: Hemoglobin ≥ 9 g/dL, White blood cell 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, Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase or serum glutamic-pyruvic transaminase (ALT/ SGPT) ≤ 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 Tuberculosis (TB) infection within 3 years
  • History of recurrent bacterial infection
  • Mycobacterium TB as indicated by a positive purified protein derivative (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 Human Immunodeficiency Virus (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 Pharmacokinetic/Pharmacodynamic (PK/PD) half-lives (whichever is longer)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866359

Locations
United States, Florida
Mayo Clinic - Rheumatology and Internal Medicine
Jacksonville, Florida, United States, 32224
United States, Massachusetts
E5, Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, New York
NYU Hospital for Joint Diseases
New York, New York, United States, 10003
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Turkey
Eskişehir Osmangazi University
Eskişehir, Turkey, 26480
University of Istanbul
Istanbul, Turkey, 34098
Selçuk University
Konya, Turkey, 42080
Sponsors and Collaborators
Celgene Corporation
Investigators
Principal Investigator: Yusuf Yazici, MD NYU Hospital for Joint Diseases
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00866359     History of Changes
Other Study ID Numbers: CC-10004-BCT-001, EudraCT#: 2008-002722-11
Study First Received: March 18, 2009
Results First Received: April 22, 2014
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration
Turkey: Ministry of Health

Additional relevant MeSH terms:
Behcet Syndrome
Mouth Diseases
Stomatognathic Diseases
Uveitis, Anterior
Panuveitis
Uveitis
Uveal Diseases
Eye Diseases
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Skin Diseases, Vascular
Skin Diseases
Apremilast
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014