Trial Outcomes & Findings for A Phase 3 Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Active Behçet's Disease (NCT NCT02307513)

Last Updated: 2021-07-22

Results Overview

The number of oral ulcers that was counted for the analysis of the primary endpoint included current and recurrent ulcers at each time point; a single oral ulcer could be recounted multiple times if it persisted or recurred at subsequent visits.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

207 participants

Primary outcome timeframe

Oral ulcers were assessed at weeks 0 (baseline), 1, 2, 4, 6, 8, 10, and 12 during the placebo-controlled period.

Results posted on

2021-07-22

Participant Flow

The study was conducted at 53 sites in Europe (France, Germany, Greece, and Italy), Asia (Japan and the Republic of Korea), the United States, and Rest of the World (Israel, Lebanon, and Turkey).

Participants were randomized in a 1:1 ratio to receive either apremilast or placebo in a blinded fashion in the placebo-controlled treatment phase. After completion of 12 weeks, all participants were to receive apremilast for 52 weeks in the active treatment phase. Participants in Germany had the opportunity to enter an optional open-label extension phase at week 64. Participants were stratified by gender, history of uveitis and region (Japan and Other Regions).

Participant milestones

Participant milestones
Measure	Placebo/Apremilast Participants received identically appearing placebo tablets twice a day (BID) from weeks 0 to 12 during the placebo-controlled treatment phase. At week 12 participants were switched to apremilast 30 mg tablets BID for 52 weeks during the active treatment phase and continued apremilast up to week 64. Participants in Germany had the option to continue receiving apremilast 30 mg BID in the extension phase.	Apremilast Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase and continued to receive apremilast 30 mg BID for 52 weeks during the active treatment phase up to week 64. Participants in Germany had the option to continue receiving apremilast 30 mg BID in the extension phase.
Placebo Controlled Phase (Weeks 0-12) STARTED	103	104
Placebo Controlled Phase (Weeks 0-12) COMPLETED	83	96
Placebo Controlled Phase (Weeks 0-12) NOT COMPLETED	20	8
Active Treatment Phase (Weeks 13-64) STARTED	83	95
Active Treatment Phase (Weeks 13-64) COMPLETED	68	75
Active Treatment Phase (Weeks 13-64) NOT COMPLETED	15	20
Long-term Extension STARTED	2	0
Long-term Extension COMPLETED	1	0
Long-term Extension NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Apremilast Participants received identically appearing placebo tablets twice a day (BID) from weeks 0 to 12 during the placebo-controlled treatment phase. At week 12 participants were switched to apremilast 30 mg tablets BID for 52 weeks during the active treatment phase and continued apremilast up to week 64. Participants in Germany had the option to continue receiving apremilast 30 mg BID in the extension phase.	Apremilast Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase and continued to receive apremilast 30 mg BID for 52 weeks during the active treatment phase up to week 64. Participants in Germany had the option to continue receiving apremilast 30 mg BID in the extension phase.
Placebo Controlled Phase (Weeks 0-12) Adverse Event	4	3
Placebo Controlled Phase (Weeks 0-12) Lack of Efficacy	8	0
Placebo Controlled Phase (Weeks 0-12) Non-Compliance with Study Drug	1	0
Placebo Controlled Phase (Weeks 0-12) Withdrawal by Subject	5	4
Placebo Controlled Phase (Weeks 0-12) Lost to Follow-up	1	0
Placebo Controlled Phase (Weeks 0-12) Protocol Violation	1	1
Active Treatment Phase (Weeks 13-64) Miscellaneous	0	1
Active Treatment Phase (Weeks 13-64) Adverse Event	4	9
Active Treatment Phase (Weeks 13-64) Lack of Efficacy	2	2
Active Treatment Phase (Weeks 13-64) Withdrawal by Subject	7	7
Active Treatment Phase (Weeks 13-64) Lost to Follow-up	1	1
Active Treatment Phase (Weeks 13-64) Pregnancy	1	0
Long-term Extension Physician Decision	1	0

Baseline Characteristics

One participant from each arm had duration of disease missing.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day (BID) from weeks 0 to 12 during the placebo-controlled treatment phase. At week 12 participants were switched to apremilast 30 mg BID for 52 weeks during the active treatment phase and continued apremilast up to week 64.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase and continued to receive apremilast 30 mg BID for 52 weeks during the active treatment phase up to week 64.	Total n=207 Participants Total of all reporting groups
Age, Continuous	40.6 Years STANDARD_DEVIATION 12.66 • n=103 Participants	39.4 Years STANDARD_DEVIATION 12.12 • n=104 Participants	40.0 Years STANDARD_DEVIATION 12.37 • n=207 Participants
Sex: Female, Male Female	63 Participants n=103 Participants	64 Participants n=104 Participants	127 Participants n=207 Participants
Sex: Female, Male Male	40 Participants n=103 Participants	40 Participants n=104 Participants	80 Participants n=207 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=103 Participants	0 Participants n=104 Participants	1 Participants n=207 Participants
Race (NIH/OMB) Asian	30 Participants n=103 Participants	32 Participants n=104 Participants	62 Participants n=207 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=103 Participants	0 Participants n=104 Participants	1 Participants n=207 Participants
Race (NIH/OMB) Black or African American	0 Participants n=103 Participants	1 Participants n=104 Participants	1 Participants n=207 Participants
Race (NIH/OMB) White	68 Participants n=103 Participants	69 Participants n=104 Participants	137 Participants n=207 Participants
Race (NIH/OMB) More than one race	0 Participants n=103 Participants	0 Participants n=104 Participants	0 Participants n=207 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=103 Participants	2 Participants n=104 Participants	5 Participants n=207 Participants
Region of the World Europe	27 Participants n=103 Participants	25 Participants n=104 Participants	52 Participants n=207 Participants
Region of the World North America	11 Participants n=103 Participants	14 Participants n=104 Participants	25 Participants n=207 Participants
Region of the World Asia	29 Participants n=103 Participants	32 Participants n=104 Participants	61 Participants n=207 Participants
Region of the World Rest of World	36 Participants n=103 Participants	33 Participants n=104 Participants	69 Participants n=207 Participants
Duration of Behcet's Disease	6.94 Years STANDARD_DEVIATION 7.966 • n=102 Participants • One participant from each arm had duration of disease missing.	6.74 Years STANDARD_DEVIATION 7.397 • n=103 Participants • One participant from each arm had duration of disease missing.	6.84 Years STANDARD_DEVIATION 7.667 • n=205 Participants • One participant from each arm had duration of disease missing.
Oral Ulcer Count	3.9 Oral ulcers STANDARD_DEVIATION 2.70 • n=103 Participants	4.2 Oral ulcers STANDARD_DEVIATION 3.65 • n=104 Participants	4.1 Oral ulcers STANDARD_DEVIATION 3.21 • n=207 Participants
Pain of Oral Ulcers Visual Analog Scale (VAS)	60.8 mm STANDARD_DEVIATION 26.92 • n=102 Participants • Includes participants with available data.	61.2 mm STANDARD_DEVIATION 27.55 • n=103 Participants • Includes participants with available data.	61.0 mm STANDARD_DEVIATION 27.17 • n=205 Participants • Includes participants with available data.
Behçet's Disease Current Activity Index (BDCAI) Score	3.6 Units on a scale STANDARD_DEVIATION 1.67 • n=102 Participants • One participant from placebo arm had activity score index missing at baseline. Includes participants with available data.	3.7 Units on a scale STANDARD_DEVIATION 1.58 • n=104 Participants • One participant from placebo arm had activity score index missing at baseline. Includes participants with available data.	3.7 Units on a scale STANDARD_DEVIATION 1.62 • n=206 Participants • One participant from placebo arm had activity score index missing at baseline. Includes participants with available data.
Behçet's Syndrome Activity Score (BSAS)	44.30 scores on a scale STANDARD_DEVIATION 16.862 • n=103 Participants	42.75 scores on a scale STANDARD_DEVIATION 16.224 • n=104 Participants	43.52 scores on a scale STANDARD_DEVIATION 16.523 • n=207 Participants
Behçet's Disease Quality of Life (BD QoL)	11.24 Units on a scale STANDARD_DEVIATION 8.157 • n=103 Participants	10.22 Units on a scale STANDARD_DEVIATION 8.245 • n=104 Participants	10.73 Units on a scale STANDARD_DEVIATION 8.197 • n=207 Participants

PRIMARY outcome

Timeframe: Oral ulcers were assessed at weeks 0 (baseline), 1, 2, 4, 6, 8, 10, and 12 during the placebo-controlled period.

Population: The intent to treat (ITT) population included all randomized participants who received at least 1 dose of study drug. Multiple imputation (MI) was used to impute missing oral ulcer counts.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Area Under the Curve (AUC) for the Number of Oral Ulcers From Baseline Through Week 12 (AUC W0-12)	222.14 Ulcers*days Standard Error 15.886	129.54 Ulcers*days Standard Error 15.943

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The ITT population with available baseline data. Last observation carried forward (LOCF) imputation was used. LOCF is the last observation (baseline value if no post-baseline assessment) is carried forward for missing values at week 12.

Pain of oral ulcers was measured using a 100 mm VAS scale. 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 recorded. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=103 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in Oral Ulcer Pain as Measured by Visual Analog Scale (VAS) at Week 12	-15.9 mm Standard Error 3.31	-40.7 mm Standard Error 3.34

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population with available baseline data. LOCF imputation was used for missing values at week 12.

The Behçet's Syndrome Activity Score (BSAS) contains 10 questions that assess the number of new oral and genital ulcers and skin lesions, GI, CNS, vascular, and ocular involvement, and the participant's current level of discomfort. The Behçet's Syndrome Activity Score ranges from 0 to 100, with a higher score indicating a higher level of disease activity. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in Disease Activity as Measured by Behçet's Syndrome Activity Score (BSAS) at Week 12	-5.41 Units on a scale Standard Error 1.776	-17.35 Units on a scale Standard Error 1.796

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population with available baseline data. LOCF imputation was used for missing values at week 12.

The Behçet's Disease Current Activity Form (BDCAF) consists of 3 component scores: the Behçet's Disease Current Activity Index (BDCAI) score, the Patient's Perception of Disease Activity, and the Clinician's Overall Perception of Disease Activity. The BDCAI consists of 12 questions regarding disease manifestations over the previous 4 weeks, including oral and genital disease activity, as well as other manifestations of BD involving the skin, joints, GI tract, eyes, nervous system, and vascular system. The BDCAI score is the sum score of 12 items and 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 n=102 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in Disease Activity as Measured by Behçet's Disease Current Activity Form (BDCAF): Behçet's Disease Current Activity Index (BDCAI) at Week 12	-0.4 Units on a scale Standard Error 0.20	-0.9 Units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population with available data. LOCF imputation was used for missing values at week 12.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in Disease Activity as Measured by Behçet's Disease Current Activity Form (BDCAF): Patient's Perception of Disease Activity at Week 12	-0.7 Units on a scale Standard Error 0.18	-1.7 Units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population with available baseline data. LOCF imputation was used for missing values at week 12.

The Behçet's Disease Current Activity Form (BDCAF) consists of 3 component scores: the Behçet's disease Current Activity Index (BDCAI) score, the Patient's Perception of Disease Activity, and the Clinician's Overall Perception of Disease Activity. The Clinician's Overall Perception of Disease Activity was assessed on a scale from 1 to 7, where a higher score indicates a higher level of disease activity and a negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in Disease Activity as Measured by Behçet's Disease Current Activity Form (BDCAF): Clinician's Overall Perception of Disease Activity at Week 12	-0.7 Units on a scale Standard Error 0.17	-1.6 Units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population

Participants who were oral ulcer-free by week 6 and remained oral ulcer-free for at least 6 consecutive weeks during the 12-week placebo-controlled treatment phase.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Percentage of Participants Who Achieved an Oral Ulcer Complete Response (Oral Ulcer-Free) by Week 6 and Remained Oral Ulcer-Free for at Least 6 Additional Weeks	4.9 Percentage of participants	29.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population

Time to oral ulcer resolution (defined as oral ulcer-free) was the time between the first dose date and the date when a complete response was achieved for the first time during the placebo-controlled treatment phase. For participants who did not achieve complete response or discontinued treatment before a complete response was achieved during the placebo-controlled treatment phase, time to event was censored at the last oral ulcer assessment date during the placebo-controlled treatment phase or the first dose date if there were no postbaseline ulcer assessments. Median and 95% confidence interval was based on Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Time to Oral Ulcer Resolution (Complete Response)	8.1 Weeks Interval 4.7 to Could not be estimated due to the low number of events at the time of analysis	2.1 Weeks Interval 2.0 to 4.0

SECONDARY outcome

Timeframe: Week 12

Population: The intent to treat population; participants with missing data at week 12 were classified as non-responders.

A complete response at week 12 was defined as participants who were oral ulcer free at week 12.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Percentage of Participants Who Experienced an Oral Ulcer Complete Response at Week 12	22.3 Percentage of participants	52.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population. LOCF was used for missing values at week 12.

The Behçet's Disease Quality of Life questionnaire was developed to measure the influence of BD on a particpant's life. It consists of 30 self-completed itemized questions that measure disease-related restrictions on the participant's activities and their emotional response to these restrictions. The total score is the sum of all 30 items (each yes scores 1 and each no scores 0), with 0 representing no influence of Behçet's disease on a participant's quality of life and 30 representing the most severe influence. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in Behçet's Disease Quality of Life (BD Qol) Scores at Week 12	-0.5 Units on a scale Standard Error 0.66	-3.5 Units on a scale Standard Error 0.67

SECONDARY outcome

Timeframe: Week 12

Population: The intent to treat population who had genital ulcers at baseline. Participants with missing data at week 12 were classified as non-responders.

A genital ulcer complete response at week 12 was defined as participants who were genital ulcer-free at week 12.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=17 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Percentage of Participants Who Experienced a Complete Response For Genital Ulcers at Week 12	41.2 Percentage of participants	70.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population who had a complete response prior to week 12.

The definition includes participants who remained oral ulcer-free through week 12 after achieving a complete response (oral ulcer-free) prior to week 12.

Outcome measures

Outcome measures
Measure	Placebo n=53 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=83 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Percentage of Participants With no Oral Ulcers Following a Complete Response	13.2 Percentage of participants	31.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline through week 12

Population: The intent to treat population who had a complete response prior to week 12.

Time to recurrence of oral ulcers following the loss of complete response (oral ulcer-free) was defined as the first instance when a participant had a reappearance of oral ulcers following a complete response, during the placebo-controlled treatment phase. For participants who did not have oral ulcer recurrence or discontinued treatment before any oral ulcer recurrence during the placebo-controlled treatment phase, time to event was censored at the last oral ulcer assessment during placebo-controlled treatment phase; For participants without any oral ulcer assessment following the first complete response, time to event was censored to the first complete response date.

Outcome measures

Outcome measures
Measure	Placebo n=53 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=83 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Time to Recurrence of Oral Ulcers Following Loss of Complete Response	2.3 Weeks Interval 2.1 to 4.1	4.6 Weeks Interval 3.1 to 6.1

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population who had a complete response prior to week 12.

Number of oral ulcers reported at the time of the first loss of complete response, ie, at the first instance when a participant had a reappearance of oral ulcers following a complete response, during the placebo-controlled treatment phase.

Outcome measures

Outcome measures
Measure	Placebo n=53 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=83 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Number of Oral Ulcers Following Loss of Complete Response Through Week 12	1.5 oral ulcers Standard Error 0.21	1.1 oral ulcers Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population who had BD skin lesions at baseline. LOCF imputation was used for missing values at week 12.

BD-related skin lesions (including acne-like lesions, folliculitis, and erythema nodosum) were evaluated according to the Static Physician's Global Assessment as follows: Score 0 = clear skin. Score 1 = mild in severity with the presence of 1 to 10 lesions (papules, pustules, cysts) or nodules at any anatomical site. Score 2 = Moderate severity; presence of 11 to 20 nodules or lesions (papules, pustules, cysts) at any anatomical site. Score 3 = Severe; presence of \> 20 nodules or lesions (papules, pustules, cysts) at any anatomical site. The total sore was calculated as the sum of the acne-like lesions, folliculitis, and erythema nodosum scores, and therefore ranges from 0 to 9, where a higher score indicates a higher level of activity. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=58 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in the Total Score of the Static Physician's Global Assessment (PGA) of Skin Lesions of BD at Week 12	-0.8 scores on a scale Standard Error 0.14	-0.9 scores on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline to week 12

Population: The intent to treat population who had genital ulcers at baseline. The last observation (baseline value if no post-baseline assessment) was carried forward for missing values at week 12.

Pain of genital ulcers was measured using a 100 mm visual analog scale. 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 recorded. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=17 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Change From Baseline in Genital Ulcer Pain as Measured by VAS Score at Week 12	-24.5 mm Standard Error 10.75	-30.0 mm Standard Error 11.22

SECONDARY outcome

Timeframe: From first dose of study drug in the placebo-controlled phase to the first dose of apremilast in the active treatment phase (12 weeks) or up to 28 days after last dose for participants who did not receive study drug at week 12, whichever was earlier.

Population: The safety population included all randomized participants who received at least 1 dose of study drug.

A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE (SAE) is any AE that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or constituted an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms; Moderate: symptoms causing moderate discomfort and local or noninvasive intervention is indicated; Severe: symptoms causing severe discomfort or pain, symptoms requiring medical/surgical intervention.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period Any TEAE	74 Participants	82 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period Any Drug-related TEAE	37 Participants	60 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period Any Severe TEAE	6 Participants	6 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period Any Serious TEAE	4 Participants	3 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period Any TEAE Leading to Drug Interruption	6 Participants	9 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period Any TEAE Leading to Drug Withdrawal	5 Participants	3 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period Any TEAE Leading to Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of apremilast (week 0 for those assigned to apremilast or week 12 for those assigned to placebo) up to 28 days after last dose; up to 56 weeks and 68 weeks in each arm respectively.

Population: The apremilast as treated (AAT) population includes participants who received at least 1 dose of apremilast at any time during the study.

The apremilast-exposure period started on the date of the first dose of apremilast (week 0 for participants assigned to apremilast or week 12 for participants who were originally assigned to placebo and switched to apremilast at week 12) and ended 28 days after last dose in the active treatment phase. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. An SAE is any AE that resulted in death; was life-threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or constituted an important medical event. The investigator assessed the severity of each event according to the grading scale: Mild: asymptomatic or mild symptoms; Moderate: symptoms causing moderate discomfort, local or noninvasive intervention indicated; Severe: symptoms causing severe discomfort or pain, requiring medical/surgical intervention.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received identically appearing placebo tablets twice a day from weeks 0 to 12 during the placebo-controlled treatment phase.	Apremilast 30 mg BID n=104 Participants Participants received apremilast 30 mg tablets BID from weeks 0 to 12 during the placebo-controlled treatment phase.
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE	70 Participants	90 Participants
Number of Participants With TEAEs During the Apremilast-Exposure Period Any Drug-related TEAE	29 Participants	64 Participants
Number of Participants With TEAEs During the Apremilast-Exposure Period Any Severe TEAE	4 Participants	17 Participants
Number of Participants With TEAEs During the Apremilast-Exposure Period Any Serious TEAE	7 Participants	10 Participants
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE Leading to Drug Interruption	10 Participants	17 Participants
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE Leading to Drug Withdrawal	3 Participants	12 Participants
Number of Participants With TEAEs During the Apremilast-Exposure Period Any TEAE Leading to Death	0 Participants	0 Participants

Adverse Events

Placebo-controlled Phase: Placebo

Serious events: 4 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo-controlled Phase: Apremilast 30 mg BID

Serious events: 3 serious events

Other events: 67 other events

Deaths: 0 deaths

Apremilast Exposure Period: Apremilast 30 mg BID

Serious events: 17 serious events

Other events: 132 other events

Deaths: 0 deaths

Open-label Extension Phase: Apremilast 30 mg BID

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

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 \> 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER