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

Behcet Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00866359
• Other study ID #: CC-10004-BCT-001
• Secondary ID: EudraCT#: 2008-0
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2009
• Est. completion date: May 1, 2012

Study information

• Verified date: June 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: May 1, 2012
• Est. primary completion date: May 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Behcet Syndrome

Intervention

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)
• 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)

Locations

Country	Name	City	State
Turkey	Eskisehir Osmangazi University	Eskisehir
Turkey	University of Istanbul	Istanbul
Turkey	Selçuk University	Konya
United States	E5, Boston University School of Medicine	Boston	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Mayo Clinic - Rheumatology and Internal Medicine	Jacksonville	Florida
United States	NYU Hospital for Joint Diseases	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 85	The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)	Baseline to Day 85
Other	Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 169	The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)	Day 1 to Day 169
Other	Percentage of Participants Who Were Genital Ulcer-free (Complete Response)	The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)	Day 1 to Day 197
Primary	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).	Day 85
Secondary	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.	Day 85
Secondary	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.	Baseline to Day 85
Secondary	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.	Day 1 to Day 85
Secondary	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.	Day 1 to Day 85
Secondary	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.	Day 1 to Day 85
Secondary	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	Day 85
Secondary	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.	Baseline and Day 85
Secondary	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.	Day 1 to Day 85 or to early termination visit
Secondary	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.	Day 1 to Day 85; maximum exposure to study drug was 13 weeks during treatment phase
Secondary	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).	Day 1 to Day 85
Secondary	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).	Day 169
Secondary	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.	Day 169
Secondary	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.	Day 1 to Day 169
Secondary	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.	Day 169
Secondary	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).	Day 1 to Day 169
Secondary	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).	Day 197
Secondary	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.	Day 197
Secondary	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.	Day 1 to Day 197
Secondary	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.	Day 1 to Day 197
Secondary	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.	Day 1 to Day 197; maximum exposure was 25.1 weeks