Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease (NCT NCT00866359)

Results Overview

The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

111 participants

Primary outcome timeframe

Day 85

Results posted on

2020-06-19

Participant Flow

The study was conducted at 3 study sites in Turkey and 3 sites in the United States. The first participant enrolled was enrolled on October 23, 2009 and the last participant enrolled was enrolled on May 08, 2012.

Eligible participants were randomized 1:1 to receive study drug (apremilast or placebo). Since the incidence and severity of Behçet's Disease differ between males and females, randomization was stratified by gender.

Participant milestones

Participant milestones
Measure	Placebo (Oral) BID Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets twice daily (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.	Placebo/Apremilast 30 mg Extension Phase (Days 86 to 169): Participants initially randomized to placebo BID started titration doses to reach 30 mg apremilast tablets BID and remained in that dose up to Day 169 in the active treatment extension phase.	Apremilast 30mg/Apremilast 30mg Extension Phase (Days 86 to 169): Participants initially randomized to receive 30 mg apremilast BID tablets in the 12-week placebo-controlled treatment phase continued to receive 30 mg apremilast tablets BID up to Day 169 in the active treatment extension phase.
Treatment Phase (Days 1 to 85) STARTED	56	55	0	0
Treatment Phase (Days 1 to 85) COMPLETED	45	50	0	0
Treatment Phase (Days 1 to 85) NOT COMPLETED	11	5	0	0
Extension Phase (Day 86 to 169) STARTED	0	0	45	50
Extension Phase (Day 86 to 169) COMPLETED	0	0	44	47
Extension Phase (Day 86 to 169) NOT COMPLETED	0	0	1	3
Observational Follow-Up Phase STARTED	0	0	54	54
Observational Follow-Up Phase COMPLETED	0	0	54	54
Observational Follow-Up Phase NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Oral) BID Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets twice daily (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.	Placebo/Apremilast 30 mg Extension Phase (Days 86 to 169): Participants initially randomized to placebo BID started titration doses to reach 30 mg apremilast tablets BID and remained in that dose up to Day 169 in the active treatment extension phase.	Apremilast 30mg/Apremilast 30mg Extension Phase (Days 86 to 169): Participants initially randomized to receive 30 mg apremilast BID tablets in the 12-week placebo-controlled treatment phase continued to receive 30 mg apremilast tablets BID up to Day 169 in the active treatment extension phase.
Treatment Phase (Days 1 to 85) Adverse Event	5	4	0	0
Treatment Phase (Days 1 to 85) Lack of Efficacy	3	0	0	0
Treatment Phase (Days 1 to 85) Withdrawal by Subject	1	0	0	0
Treatment Phase (Days 1 to 85) Protocol Violation	1	1	0	0
Treatment Phase (Days 1 to 85) Other	1	0	0	0
Extension Phase (Day 86 to 169) Adverse Event	0	0	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets BID in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.	Total n=111 Participants Total of all reporting groups
Age, Continuous	34.7 years STANDARD_DEVIATION 10.97 • n=5 Participants	34.3 years STANDARD_DEVIATION 9.11 • n=7 Participants	34.5 years STANDARD_DEVIATION 10.05 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	39 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Duration of Behçet's disease	5.72 years STANDARD_DEVIATION 6.084 • n=5 Participants	4.92 years STANDARD_DEVIATION 3.982 • n=7 Participants	5.33 years STANDARD_DEVIATION 5.143 • n=5 Participants

PRIMARY outcome

Timeframe: Day 85

Population: Intent to Treat (ITT) = all randomized participants with at least one oral ulcer evaluation (including the baseline visit). A Last Observation Carried Forward (LOCF) approach was applied for participants terminated early. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Number of Oral Ulcers at Day 85	2.0 ulcers/participants Standard Error 0.28	0.4 ulcers/participants Standard Error 0.28

SECONDARY outcome

Timeframe: Day 85

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Pain of Oral Ulcers as Measured by Visual Analog Scale (VAS) at Day 85	36.7 units on a scale Standard Error 3.23	9.9 units on a scale Standard Error 3.30

SECONDARY outcome

Timeframe: Baseline to Day 85

Population: Not analyzed due to low numbers of genital ulcers; not considered meaningful.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to Day 85

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Area Under the Curve (AUC) for the Number of Oral Ulcers From Day 1 to 85	157.82 total AUC (#ulcers*days) Standard Error 12.890	67.74 total AUC (#ulcers*days) Standard Error 13.267

SECONDARY outcome

Timeframe: Day 1 to Day 85

Population: No population analyzed due to small number of participants with genital ulcers; not considered meaningful.

Area under curve (AUC\^85) from Day 1 to Day 85 for the number of genital ulcers per day was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to Day 85

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Area Under the Curve (AUC) for the Number of Oral Plus Genital Ulcers From Day 1 to 85	193.95 total AUC (#ulcers*days) Standard Deviation 161.492	65.79 total AUC (#ulcers*days) Standard Deviation 108.037

SECONDARY outcome

Timeframe: Day 85

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

Sum of the number oral ulcers, genital ulcers or oral plus genital ulcers at Day 85

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Sum of the Number Oral Ulcers, Genital Ulcers or Oral Plus Genital Ulcers at Day 85	2.3 Ulcers/participants Standard Error 0.35	0.6 Ulcers/participants Standard Error 0.36

SECONDARY outcome

Timeframe: Baseline and Day 85

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Percentage of Participants Who Were Oral Ulcer-free (Complete Response), or Whose Oral Ulcers Were Reduced by ≥ 50%, (Partial Response) Complete Response	28.6 percentage of participants	70.9 percentage of participants
Percentage of Participants Who Were Oral Ulcer-free (Complete Response), or Whose Oral Ulcers Were Reduced by ≥ 50%, (Partial Response) Partial Response	50.0 percentage of participants	89.1 percentage of participants

SECONDARY outcome

Timeframe: Day 1 to Day 85 or to early termination visit

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=54 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 85	-0.1 units on a scale Standard Error 0.22	-1.2 units on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Day 1 to Day 85; maximum exposure to study drug was 13 weeks during treatment phase

Population: Safety Population defined as all participants who were randomized and received at least 1 dose of Investigational Product.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase Any TEAE	50 participants	49 participants
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase Any drug related TEAE	24 participants	30 participants
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase Any severe TEAE	5 participants	5 participants
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase Any serious TEAE	3 participants	2 participants
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase Any serious drug related TEAE	1 participants	0 participants
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase Any TEAE leading to drug interruption	0 participants	1 participants
Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase Any TEAE leading to drug withdrawal	5 participants	4 participants

SECONDARY outcome

Timeframe: Day 1 to Day 85

Population: Safety population included all participants who were randomized and received at least 1 dose of Investigational Product.

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).

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=56 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Number of New Manifestations of Behçet's Disease or Flare During the Placebo Controlled Treatment Phase Participants who had disease flare	27 participants	12 participants
Number of New Manifestations of Behçet's Disease or Flare During the Placebo Controlled Treatment Phase Participants with new onset or worsening uveitis	3 participants	0 participants

SECONDARY outcome

Timeframe: Day 169

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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).

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=45 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=49 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Number of Oral Ulcers at Day 169	0.4 ulcers/participant Standard Deviation 1.31	0.6 ulcers/participant Standard Deviation 1.27

SECONDARY outcome

Timeframe: Day 169

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=45 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=47 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 169	9.6 units on a scale Standard Deviation 21.13	9.7 units on a scale Standard Deviation 20.33

SECONDARY outcome

Timeframe: Day 1 to Day 169

Population: Not analyzed due to low numbers of genital ulcers; not considered meaningful.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 169

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=45 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=49 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Behçet's Disease (BD) Current Activity Index Form Score at Day 169	1.4 units on a scale Standard Deviation 1.18	1.6 units on a scale Standard Deviation 1.62

SECONDARY outcome

Timeframe: Day 1 to Day 169

Population: The ITT population included all randomized participants with at least one oral ulcer evaluation (including the baseline evaluation). A LOCF approach was applied for participants terminated early from the study. If a participant had no post-baseline oral ulcer assessment, the baseline value was carried forward for calculation.

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).

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=45 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Number of New Manifestations of Behçet's Disease or Flare That Were Not Present at Day 1 Participants who experienced a disease flare	15 participants	19 participants
Number of New Manifestations of Behçet's Disease or Flare That Were Not Present at Day 1 Participants with new onset or worsening uveitis	1 participants	2 participants

SECONDARY outcome

Timeframe: Day 197

Population: Includes participants who entered the Observational Follow-up Phase from either the Treatment Phase or the Extension Phase

The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=54 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=54 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Number of Oral Ulcers at Day 197	1.6 ulcers/participants Standard Deviation 1.78	1.7 ulcers/participants Standard Deviation 2.06

SECONDARY outcome

Timeframe: Day 197

Population: Includes participants who entered the Observational Follow-up Phase from either the Treatment Phase or the Extension Phase.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=54 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=54 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 197	21.0 units on a scale Standard Deviation 22.26	27.2 units on a scale Standard Deviation 28.71

SECONDARY outcome

Timeframe: Day 1 to Day 197

Population: Not analyzed due to low numbers of genital ulcers; not considered meaningful.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to Day 197

Population: Includes participants who entered the Observational Follow-up Phase from either the Treatment Phase or the Extension Phase

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=53 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=53 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 197	-0.6 units on a scale Standard Deviation 1.28	-1.2 units on a scale Standard Deviation 1.65

SECONDARY outcome

Timeframe: Day 1 to Day 197; maximum exposure was 25.1 weeks

Population: Safety analyses for the apremilast-exposure period was based on the apremilast participants as treated (AAT) Population, and included those who were randomized (at the randomization visit) or switched (at the Day 85 visit) to apremilast 30 mg BID, and received at least one dose of apremilast after the initial randomization or switch to 30 mg BID.

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.

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=45 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=55 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase Any severe TEAE	1 particpants	11 particpants
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase Any TEAE	39 particpants	50 particpants
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase Any drug related TEAE	20 particpants	33 particpants
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase Any serious TEAE	1 particpants	5 particpants
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase Any serious drug related TEAE	0 particpants	1 particpants
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase TEAE leading to drug interuption	0 particpants	1 particpants
Summary of Treatment Emergent Adverse Events During the Active Treatment-Extension Phase TEAE leading to drug withdrawal	1 particpants	7 particpants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 85

Population: Intent to Treat (ITT) = all randomized participants with at least one genital ulcer at baseline. A Last Observation Carried Forward (LOCF) approach was applied for participants terminated early. If a participant had no post-baseline genital ulcer assessment, the baseline value was carried forward for calculation.

The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=6 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=10 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 85	50 percentage of participants	100 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 169

Population: Intent to Treat (ITT) = all randomized participants with at least one genital ulcer at baseline visit. A Last Observation Carried Forward (LOCF) approach was applied for participants terminated early. If a participant had no post-baseline genital ulcer assessment, the baseline value was carried forward for calculation.

The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=6 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=10 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 169	66.7 percentage of participants	100 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 197

Population: Intent to Treat (ITT) = all randomized participants with at least one genital ulcer at baseline. A Last Observation Carried Forward (LOCF) approach was applied for participants terminated early. If a participant had no post-baseline genital ulcer assessment, the baseline value was carried forward for calculation.

The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)

Outcome measures

Outcome measures
Measure	Placebo (Oral) BID n=6 Participants Treatment Phase (Days 1 to 85): Participants administered identically matching placebo tablets (BID) in the 12-week placebo-controlled phase.	Apremilast 30mg (Oral) BID n=10 Participants Treatment Phase (Days 1 to 85): Participants administered to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase.
Percentage of Participants Who Were Genital Ulcer-free (Complete Response)	100 percentage of participants	100 percentage of participants

Adverse Events

Week 12: Placebo BID

Serious events: 3 serious events

Other events: 48 other events

Deaths: 0 deaths

Week 12: Apremilast 30 mg BID

Serious events: 2 serious events

Other events: 47 other events

Deaths: 0 deaths

Week 24: Apremilast 30 mg BID

Serious events: 6 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Week 12: Placebo BID n=56 participants at risk Participants randomized to placebo tablets twice daily during the placebo-controlled phase. Includes data through Week 12 for all participants randomized to placebo.	Week 12: Apremilast 30 mg BID n=55 participants at risk Participants randomized to 30 mg Apremilast tablets BID during the 12-week placebo-controlled treatment phase. Includes data through Week 12 for all participants randomized to 30mg Apremilast BID.	Week 24: Apremilast 30 mg BID n=100 participants at risk Participants who received 30 mg apremilast, regardless of when the apremilast exposure started (at Week 0, or 12), up until Week 24. Includes data through Week 24 for participants who were treated with Apremilast started at Week 0 and data from Week 12 through Week 24 for participants who were treated with Apremilast started at Week 12.
Immune system disorders Behçet's Syndrome	3.6% 2/56 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	0.00% 0/55 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	3.0% 3/100 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase
Nervous system disorders Diplegia	0.00% 0/56 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	1.8% 1/55 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	1.0% 1/100 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase
Gastrointestinal disorders Anal Fissure	0.00% 0/56 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	1.8% 1/55 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	1.0% 1/100 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase
Gastrointestinal disorders Haemorrhoids	0.00% 0/56 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	1.8% 1/55 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	1.0% 1/100 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase
Gastrointestinal disorders Pyrexia	1.8% 1/56 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	0.00% 0/55 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	0.00% 0/100 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase
Infections and infestations Influenza	0.00% 0/56 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	0.00% 0/55 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase	1.0% 1/100 • Days 1 to Day 197 visit; maximum exposure to study drug was 25.1 weeks. From Day 1 (first dose) through the end of the follow up period up to 28 days after the last dose of study drug. 108 participants were part of the follow-up phase (had prematurely discontinued therapy during the placebo (PBO)-controlled phase but had completed PBO-controlled phase and prematurely discontinued therapy during the extension phase. Those who prematurely discontinued therapy during the PBO-controlled phase did not participate the extension phase

Other adverse events

Additional Information

Anne McClain

Celgene Corporation

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 45 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential data before submission or defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER