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

Primary Purpose

Behçet's Syndrome

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Apremilast

Placebo

About this trial

This is an interventional treatment trial for Behçet's Syndrome focused on measuring APREMILAST (CC-10004), CC-10004, Efficacy, Safety, Phase 3, Behçet's Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
Male and female subjects ≥ 18 years of age at the time of signing the informed consent document.
Able to adhere to the study visit schedule and other protocol requirements.
Diagnosed with Behcet's disease meeting th4 International Study Group (ISG) criteria,
Oral ulcers that occurred at least 3 times in the previous 12-month period, including oral ulcers at the screening visit.
Subjects must have at least 2 oral ulcers at Visit 1 (Screening Visit), and:
1. At least 2 oral ulcers at Visit 2 (day of randomization), when Visit 2 occurs at least 14 days after Visit 1. OR
2. At least 3 oral ulcers at Visit 2 (day of randomization), when Visit 2 occurs at any time between 1 day and 42 days after Visit 1.
Have prior treatment with at least 1 non-biologic Behçet's disease therapy, such as, but not limited to, topical corticosteroids, or systemic treatment.
Candidate for systemic therapy, for the treatment of oral ulcers.
a. A candidate for systemic therapy is a subject judged by the study Investigator as someone whose mucocutaneous ulcers are considered inappropriate for topical therapy based on the severity of disease and extent of the affected area, or whose oral ulcers cannot be adequately controlled by topical therapy.
Laboratory Measures: Must meet the following laboratory measures:
- Hemoglobin > 9 g/dL
- White blood cell (WBC) count ≥ 3000 /L(≥ 3.0 X 10^9/L) and ≤ 14,000/L (≤ 14 X 10^9/L )
- Platelet count ≥ 100,000 /L (≥ 100 X 10^9/L)
- Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
- Total bilirubin ≤ 2.0 mg/dL
- Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≥ 1.5 X ULN. Subjects who fail screening due to ≥ 1.5 X ULN AST/SGOT and/or ALT/SGPT will be allowed to repeat AST/SGOT and/or ALT/SGPT tests within the screening phase. Repeat test results should be ≤ ULN (within reference range) to be eligible.

Laboratory tests will be allowed to be repeated 1 time if, in the Investigator's clinical judgment, there is a reasonable possibility of the repeat tests not meeting the exclusion values, and with concurrence from the Medical Monitor.

Contraception Requirements:

All Females of Child Bearing Potential (FCBP) must use one of the approved contraceptive options as described below while taking apremilast and for at least 28 days after administration of the last dose of the apremilast.

At the time of study entry, and at any time during the study when a FCBP's contraceptive measures or ability to become pregnant changes, the Investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy.

All FCBP must have a negative pregnancy test at Visits 1 and 2. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below:

Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex or non-latex condoms NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least 28 days after the last dose of IP.

Exclusion Criteria: The presence of any of the following will exclude a subject from the study enrollment.

Disease Specific Exclusions:

Behçet's disease-related active major organ involvement - pulmonary (eg, pulmonary artery aneurysm), vascular (eg, thrombophlebitis), gastrointestinal (eg, ulcers along the gastrointestinal tract), and central nervous systems (eg, meningoencephalitis) manifestations, and ocular lesions (eg, uveitis) requiring immunosuppressive therapy; however:
1. Previous major organ involvement is allowed if it occurred at least 1 year prior to Visit 1 (Screening Visit) and is not active at time of enrollment.
2. Subjects with mild BD-related ocular lesions not requiring systemic immunosuppressive therapy are allowed.
3. Subjects with BD-related arthritis and BD-skin manifestations are also allowed.
Previous exposure to biologic therapies for the treatment of BD oral ulcers ( Previous biologic therapy exposure is allowed for other indications, including other manifestations of BD)
Prior use of apremilast.
Use of any investigational medication within 4 weeks prior to Visit 2 or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer).
Current use of strong cytochrome P450 enzyme inducers (eg, rifampin, phenobarbital, carbamazepine, phenytoin)
Having received concomitant immune modulating therapy (except oral or topical corticosteroids) within:
- Seven days prior to Visit 2 (Baseline Visit; day of randomization) for colchicines
- Ten days prior to Visit 2 (Baseline Visit; day of randomization) for azathioprine and mycophenolate mofetil
- Four weeks (28 days) prior to Visit 2 (Baseline Visit; day of randomization) for cyclosporine, methotrexate, cyclophosphamide, thalidomide, and dapsone.
Note: Oral and topical corticosteroids must have been tapered as appropriate and discontinued prior to the day of Visit 2 (day of randomization).
- At least 5 terminal half-lives for all biologics, including, but not limited to, those listed below; within:
- Four weeks prior to Visit 2 (Baseline Visit; day of randomization) for etanercept
- Eight weeks prior to Visit 2 (Baseline Visit; day of randomization) for infliximab
- Ten weeks prior to Visit 2 (Baseline Visit; day of randomization) for adalimumab, golimumab, certolizumab, abatacept, and tocilizumab
- Six months prior to Visit 2 (Baseline Visit; day of randomization) for secukinumab
Having received intra-articular or parenteral corticosteroids within 6 weeks (42 days) prior to Visit 2 (Baseline Visit; day of randomization).
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
Inability to provide voluntary consent.
Pregnant women or breast feeding mothers.
Systemic or opportunistic fungal infection.
Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C and herpes zoster, histoplasmosis, coccidiomycosis, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of the Screening Phase.
Clinically significant abnormality on chest radiograph.
Clinically significant abnormality on 12-lead electrocardiogram (ECG).
History of positive test for, or any clinical suspicion of, human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
Malignancy or history of malignancy, except for:
1. treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;
2. treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years of Visit 1.
Any condition that confounds the ability to interpret data from the study.
Scheduled surgery or other interventions that would interrupt the subject's participation in the study.
Prior history of suicide attempt at any time in the subject's lifetime prior to Visit 2 (Baseline Visit; day of randomization) or major psychiatric illness requiring hospitalization within 3 years prior to Visit 2 (Baseline Visit; day of randomization).

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Placebo / Apremilast

Apremilast

Arm Description

Participants randomized to this arm will receive placebo tablets twice daily by mouth for the first twelve weeks followed by 52 weeks of 30 mg apremilast tablets twice daily by mouth.

Participants randomized to this arm will receive 30 mg apremilast tablets twice daily by mouth for 64 weeks.

Outcomes

Primary Outcome Measures

Area Under the Curve (AUC) for the Number of Oral Ulcers From Baseline Through Week 12 (AUC W0-12)

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.

Secondary Outcome Measures

Change From Baseline in Oral Ulcer Pain as Measured by Visual Analog Scale (VAS) 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.

Change From Baseline in Disease Activity as Measured by Behçet's Syndrome Activity Score (BSAS) 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.

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

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.

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

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

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.

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

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.

Time to Oral Ulcer Resolution (Complete Response)

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.

Percentage of Participants Who Experienced an Oral Ulcer Complete Response at Week 12

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

Change From Baseline in Behçet's Disease Quality of Life (BD Qol) Scores 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.

Percentage of Participants Who Experienced a Complete Response For Genital Ulcers at Week 12

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

Percentage of Participants With no Oral Ulcers Following a Complete Response

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

Time to Recurrence of Oral Ulcers Following Loss of Complete Response

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.

Number of Oral Ulcers Following Loss of Complete Response Through 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.

Change From Baseline in the Total Score of the Static Physician's Global Assessment (PGA) of Skin Lesions of BD 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.

Change From Baseline in Genital Ulcer Pain as Measured by VAS Score 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.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period

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.

Number of Participants With TEAEs During the Apremilast-Exposure Period

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.

Full Information

NCT ID

NCT02307513

First Posted

December 2, 2014

Last Updated

July 2, 2021

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT02307513

Brief Title

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

Official Title

A Phase 3, Multicenter, Randomized, Doubleblind, Placebo-controlled, Parallel Group Study, Followed by an Active-treatment Phase to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Subjects With Active Behcet's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

December 30, 2014 (Actual)

Primary Completion Date

September 25, 2017 (Actual)

Study Completion Date

July 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The main objective of this study is to evaluate the efficacy and safety of apremilast in the treatment of oral ulcers in adults with active Behçet's disease (BD).

Detailed Description

Behçet's disease, is a rare disorder that causes inflammation in blood vessels throughout the body. The signs and symptoms of Behçet's disease may include mouth sores, eye inflammation, skin rashes and lesions, and genital sores that vary from person to person and may come and go on their own. The exact cause of Behçet's is unknown, but it may be an autoimmune disorder, which means the body's immune system mistakenly attacks some of its own healthy cells. This study will evaluate if apremilast is better than placebo (inactive substance in the same form as the drug) for the treatment of oral ulcers in subjects with active Behçet's disease. Other manifestations of the disease will also be assessed, such as, pain and tenderness in joints, eye inflammation, genital ulcers, and skin disease. This study also will test how well the body tolerates apremilast. In addition, the second purpose of the study is to assess the safety of apremilast in patients with Behçet's disease. This study is a randomized, placebo-controlled, parallel design. The placebo-controlled period will be 12 weeks long and participants will receive apremilast or placebo. After the 12-week placebo-controlled period, all participants will receive apremilast for 52 weeks in the active treatment period. All participants will have their final study visit 4 weeks after stopping apremilast treatment. Participants in Germany will have the opportunity to enter an optional open-label extension phase after the 52-week active treatment phase (week 64 visit), and continue until apremilast is commercially available for Behçet's disease or until apremilast is found not to be acceptable for Behçet's disease, according to either the sponsor or health authority.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Behçet's Syndrome

Keywords

APREMILAST (CC-10004), CC-10004, Efficacy, Safety, Phase 3, Behçet's Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

207 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo / Apremilast

Arm Type

Experimental

Arm Description

Participants randomized to this arm will receive placebo tablets twice daily by mouth for the first twelve weeks followed by 52 weeks of 30 mg apremilast tablets twice daily by mouth.

Arm Title

Apremilast

Arm Type

Experimental

Arm Description

Participants randomized to this arm will receive 30 mg apremilast tablets twice daily by mouth for 64 weeks.

Intervention Type

Drug

Intervention Name(s)

Apremilast

Other Intervention Name(s)

Otezla®, CC-10004

Intervention Description

Tablets for oral administration

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Tablets for oral administration

Primary Outcome Measure Information:

Title

Area Under the Curve (AUC) for the Number of Oral Ulcers From Baseline Through Week 12 (AUC W0-12)

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Change From Baseline in Oral Ulcer Pain as Measured by Visual Analog Scale (VAS) at Week 12

Description

Time Frame

Baseline to week 12

Title

Change From Baseline in Disease Activity as Measured by Behçet's Syndrome Activity Score (BSAS) at Week 12

Description

Time Frame

Baseline to week 12

Title

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

Description

Time Frame

Baseline to week 12

Title

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

Description

Time Frame

Baseline to week 12

Title

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

Description

Time Frame

Baseline to week 12

Title

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

Description

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.

Time Frame

Baseline to week 12

Title

Time to Oral Ulcer Resolution (Complete Response)

Description

Time Frame

Baseline to week 12

Title

Percentage of Participants Who Experienced an Oral Ulcer Complete Response at Week 12

Description

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

Time Frame

Week 12

Title

Change From Baseline in Behçet's Disease Quality of Life (BD Qol) Scores at Week 12

Description

Time Frame

Baseline to week 12

Title

Percentage of Participants Who Experienced a Complete Response For Genital Ulcers at Week 12

Description

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

Time Frame

Week 12

Title

Percentage of Participants With no Oral Ulcers Following a Complete Response

Description

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

Time Frame

Baseline to week 12

Title

Time to Recurrence of Oral Ulcers Following Loss of Complete Response

Description

Time Frame

Baseline through week 12

Title

Number of Oral Ulcers Following Loss of Complete Response Through Week 12

Description

Time Frame

Baseline to week 12

Title

Change From Baseline in the Total Score of the Static Physician's Global Assessment (PGA) of Skin Lesions of BD at Week 12

Description

Time Frame

Baseline to week 12

Title

Change From Baseline in Genital Ulcer Pain as Measured by VAS Score at Week 12

Description

Time Frame

Baseline to week 12

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period

Description

Time Frame

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.

Title

Number of Participants With TEAEs During the Apremilast-Exposure Period

Description

Time Frame

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. Male and female subjects ≥ 18 years of age at the time of signing the informed consent document. Able to adhere to the study visit schedule and other protocol requirements. Diagnosed with Behcet's disease meeting th4 International Study Group (ISG) criteria, Oral ulcers that occurred at least 3 times in the previous 12-month period, including oral ulcers at the screening visit. Subjects must have at least 2 oral ulcers at Visit 1 (Screening Visit), and: At least 2 oral ulcers at Visit 2 (day of randomization), when Visit 2 occurs at least 14 days after Visit 1. OR At least 3 oral ulcers at Visit 2 (day of randomization), when Visit 2 occurs at any time between 1 day and 42 days after Visit 1. Have prior treatment with at least 1 non-biologic Behçet's disease therapy, such as, but not limited to, topical corticosteroids, or systemic treatment. Candidate for systemic therapy, for the treatment of oral ulcers. a. A candidate for systemic therapy is a subject judged by the study Investigator as someone whose mucocutaneous ulcers are considered inappropriate for topical therapy based on the severity of disease and extent of the affected area, or whose oral ulcers cannot be adequately controlled by topical therapy. Laboratory Measures: Must meet the following laboratory measures: Hemoglobin > 9 g/dL White blood cell (WBC) count ≥ 3000 /L(≥ 3.0 X 10^9/L) and ≤ 14,000/L (≤ 14 X 10^9/L ) Platelet count ≥ 100,000 /L (≥ 100 X 10^9/L) Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L) Total bilirubin ≤ 2.0 mg/dL Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≥ 1.5 X ULN. Subjects who fail screening due to ≥ 1.5 X ULN AST/SGOT and/or ALT/SGPT will be allowed to repeat AST/SGOT and/or ALT/SGPT tests within the screening phase. Repeat test results should be ≤ ULN (within reference range) to be eligible. Laboratory tests will be allowed to be repeated 1 time if, in the Investigator's clinical judgment, there is a reasonable possibility of the repeat tests not meeting the exclusion values, and with concurrence from the Medical Monitor. Contraception Requirements: All Females of Child Bearing Potential (FCBP) must use one of the approved contraceptive options as described below while taking apremilast and for at least 28 days after administration of the last dose of the apremilast. At the time of study entry, and at any time during the study when a FCBP's contraceptive measures or ability to become pregnant changes, the Investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy. All FCBP must have a negative pregnancy test at Visits 1 and 2. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex or non-latex condoms NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least 28 days after the last dose of IP. Exclusion Criteria: The presence of any of the following will exclude a subject from the study enrollment. Disease Specific Exclusions: Behçet's disease-related active major organ involvement - pulmonary (eg, pulmonary artery aneurysm), vascular (eg, thrombophlebitis), gastrointestinal (eg, ulcers along the gastrointestinal tract), and central nervous systems (eg, meningoencephalitis) manifestations, and ocular lesions (eg, uveitis) requiring immunosuppressive therapy; however: Previous major organ involvement is allowed if it occurred at least 1 year prior to Visit 1 (Screening Visit) and is not active at time of enrollment. Subjects with mild BD-related ocular lesions not requiring systemic immunosuppressive therapy are allowed. Subjects with BD-related arthritis and BD-skin manifestations are also allowed. Previous exposure to biologic therapies for the treatment of BD oral ulcers ( Previous biologic therapy exposure is allowed for other indications, including other manifestations of BD) Prior use of apremilast. Use of any investigational medication within 4 weeks prior to Visit 2 or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer). Current use of strong cytochrome P450 enzyme inducers (eg, rifampin, phenobarbital, carbamazepine, phenytoin) Having received concomitant immune modulating therapy (except oral or topical corticosteroids) within: Seven days prior to Visit 2 (Baseline Visit; day of randomization) for colchicines Ten days prior to Visit 2 (Baseline Visit; day of randomization) for azathioprine and mycophenolate mofetil Four weeks (28 days) prior to Visit 2 (Baseline Visit; day of randomization) for cyclosporine, methotrexate, cyclophosphamide, thalidomide, and dapsone. Note: Oral and topical corticosteroids must have been tapered as appropriate and discontinued prior to the day of Visit 2 (day of randomization). At least 5 terminal half-lives for all biologics, including, but not limited to, those listed below; within: Four weeks prior to Visit 2 (Baseline Visit; day of randomization) for etanercept Eight weeks prior to Visit 2 (Baseline Visit; day of randomization) for infliximab Ten weeks prior to Visit 2 (Baseline Visit; day of randomization) for adalimumab, golimumab, certolizumab, abatacept, and tocilizumab Six months prior to Visit 2 (Baseline Visit; day of randomization) for secukinumab Having received intra-articular or parenteral corticosteroids within 6 weeks (42 days) prior to Visit 2 (Baseline Visit; day of randomization). Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. Inability to provide voluntary consent. Pregnant women or breast feeding mothers. Systemic or opportunistic fungal infection. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C and herpes zoster, histoplasmosis, coccidiomycosis, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of the Screening Phase. Clinically significant abnormality on chest radiograph. Clinically significant abnormality on 12-lead electrocardiogram (ECG). History of positive test for, or any clinical suspicion of, human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease). Malignancy or history of malignancy, except for: treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years of Visit 1. Any condition that confounds the ability to interpret data from the study. Scheduled surgery or other interventions that would interrupt the subject's participation in the study. Prior history of suicide attempt at any time in the subject's lifetime prior to Visit 2 (Baseline Visit; day of randomization) or major psychiatric illness requiring hospitalization within 3 years prior to Visit 2 (Baseline Visit; day of randomization).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Arizona Arthritis and Rheumatology Research, PLLC

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85032

Country

United States

Facility Name

University of California Davis Medical Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95816

Country

United States

Facility Name

Millennium Research

City

Ormond Beach

State/Province

Florida

ZIP/Postal Code

32174

Country

United States

Facility Name

Arthritis and Rheumatology of Georgia

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

Northwestern University Feinberg School of Medicine

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Advanced Rheumatology

City

Lansing

State/Province

Michigan

ZIP/Postal Code

48910

Country

United States

Facility Name

Shores Rheumatology

City

Saint Clair Shores

State/Province

Michigan

ZIP/Postal Code

48081

Country

United States

Facility Name

University of New Mexico

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87131

Country

United States

Facility Name

New York Methodist Hospital

City

Brooklyn

State/Province

New York

ZIP/Postal Code

11215

Country

United States

Facility Name

NYU Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

University of Pennsylvania Health Systems

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Hopital de La Conception

City

Marseille Cedex 05

ZIP/Postal Code

13385

Country

France

Facility Name

Pitié-Salpêtriere Hospital Paris

City

Paris

ZIP/Postal Code

75013

Country

France

Facility Name

Hopital Cochin

City

Paris

ZIP/Postal Code

75014

Country

France

Facility Name

Hospital Saint Louis

City

Paris

ZIP/Postal Code

75475

Country

France

Facility Name

Charite Universitaetsmedizin Berlin

City

Berlin

ZIP/Postal Code

10107

Country

Germany

Facility Name

Stadtisches Klinikum Dessau

City

Dessau

ZIP/Postal Code

06847

Country

Germany

Facility Name

Asklepios Rheumazentrum Hamburg

City

Hamburg

ZIP/Postal Code

22763

Country

Germany

Facility Name

Navy Hospital of Athens

City

Athens

ZIP/Postal Code

115 21

Country

Greece

Facility Name

Athens General Hospital 'G Gennimatas'

City

Athens

ZIP/Postal Code

115 27

Country

Greece

Facility Name

Laiko General Hospital of Athens

City

Athens

ZIP/Postal Code

11527

Country

Greece

Facility Name

Ippokratio General Hospital of Thessaloniki

City

Thessaloniki

ZIP/Postal Code

54642

Country

Greece

Facility Name

Bnai Zion Medical Center

City

Haifa

ZIP/Postal Code

31048

Country

Israel

Facility Name

Rambam Health Care Campus

City

Haifa

ZIP/Postal Code

31096

Country

Israel

Facility Name

Hadassah Medical Organization

City

Jerusalem

ZIP/Postal Code

91120

Country

Israel

Facility Name

Rabin Medical Center

City

Petah Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

Chaim Sheba Medical Center

City

Ramat Gan

ZIP/Postal Code

52621

Country

Israel

Facility Name

Azienda Ospedaliero Universitaria Careggi

City

Firenze

ZIP/Postal Code

50134

Country

Italy

Facility Name

Azienda Ospedaliera Regionale San Carlo

City

Potenza/Matera

ZIP/Postal Code

85100

Country

Italy

Facility Name

Arcispedale Santa Maria Nuova

City

Reggio Emilia

ZIP/Postal Code

42100

Country

Italy

Facility Name

Medical Hospital of Tokyo Medical and Dental University

City

Bunkyo-ku, Tokyo

ZIP/Postal Code

113-8519

Country

Japan

Facility Name

Nippon Medical School Hospital

City

Bunkyo-ku

ZIP/Postal Code

113-8602

Country

Japan

Facility Name

St. Luke's International Hospital

City

Chuo-ku

ZIP/Postal Code

104-8560

Country

Japan

Facility Name

Tokyo Metropolitan Tama Medical Center

City

Fuchu-shi

ZIP/Postal Code

183-8524

Country

Japan

Facility Name

Japanese Red Cross Society Himeji Hospital

City

Himeji-shi

ZIP/Postal Code

670-8540

Country

Japan

Facility Name

Saitama Medical University Hospital

City

Iruma-gun, Saitama

ZIP/Postal Code

350-0495

Country

Japan

Facility Name

Teikyo University Hospital

City

Itabashi-ku

ZIP/Postal Code

173-8606

Country

Japan

Facility Name

Nihon University Itabashi Hospital

City

Itabashi-ku

ZIP/Postal Code

173-8610

Country

Japan

Facility Name

St Marianna University School of Medicine Hospital

City

Kawasaki, Kanagawa

ZIP/Postal Code

216-8511

Country

Japan

Facility Name

University of Occupational and Environmentall Health

City

Kitakyushu

ZIP/Postal Code

807-8556

Country

Japan

Facility Name

Kagawa University Hospital

City

Miki-cho

ZIP/Postal Code

761-0793

Country

Japan

Facility Name

Kitasato University Hospital

City

Sagamihara

ZIP/Postal Code

228-8555

Country

Japan

Facility Name

Saga Medical School Hospital

City

Saga

ZIP/Postal Code

849-8501

Country

Japan

Facility Name

Sapporo Medical University Hospital

City

Sapporo, Hokkaidô

ZIP/Postal Code

060-8543

Country

Japan

Facility Name

Hokkaido University Hospital

City

Sapporo, Hokkaidô

ZIP/Postal Code

060-8648

Country

Japan

Facility Name

Shimonoseki City Hospital

City

Shimonoseki

ZIP/Postal Code

750-8520

Country

Japan

Facility Name

Tokyo Medical University Hospital

City

Shinjyuku-ku

ZIP/Postal Code

160-0023

Country

Japan

Facility Name

Tomishiro Central Hospital

City

Tomigusuku-shi

ZIP/Postal Code

901-0243

Country

Japan

Facility Name

Ehime University Hospital

City

Toon

ZIP/Postal Code

791-0295

Country

Japan

Facility Name

Yokohama City University Hospital

City

Yokohama, Kanagawa

ZIP/Postal Code

213-8507

Country

Japan

Facility Name

Chungnam National University Hospital

City

Daejeon

ZIP/Postal Code

302799

Country

Korea, Republic of

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Severance Hospital, Yonsei University Health System

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

Konkuk University Hospital

City

Seoul

ZIP/Postal Code

143-729

Country

Korea, Republic of

Facility Name

Ajou University Hospital

City

Suwon si

ZIP/Postal Code

16499

Country

Korea, Republic of

Facility Name

Hotel Dieu de France

City

Beirut

Country

Lebanon

Facility Name

Ain Wazein Hospital

City

El Chouf

Country

Lebanon

Facility Name

American University of Beirut Medical Center

City

El Chouf

Country

Lebanon

Facility Name

Cukurova University Medical Faculty Balcali Hospital

City

Adana

ZIP/Postal Code

01330

Country

Turkey

Facility Name

Eskisehir Osmangazi University

City

Eskisehir

ZIP/Postal Code

26480

Country

Turkey

Facility Name

Istanbul Universitesi Cerrahpasa Tip Fakultesi

City

Istanbul

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Marmara University Hospital

City

Istanbul

ZIP/Postal Code

34899

Country

Turkey

Facility Name

Selcuk University Medical Faculty

City

Konya

ZIP/Postal Code

42080

Country

Turkey

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

IPD Sharing Time Frame

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

IPD Sharing Access Criteria

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

IPD Sharing URL

https://www.amgen.com/datasharing

Citations:

PubMed Identifier

35798511

Citation

Hatemi G, Mahr A, Takeno M, Kim D, Melikoglu M, Cheng S, McCue S, Paris M, Chen M, Yazici Y. Impact of apremilast on quality of life in Behcet's syndrome: analysis of the phase 3 RELIEF study. RMD Open. 2022 Jul;8(2):e002235. doi: 10.1136/rmdopen-2022-002235.

Results Reference

derived

PubMed Identifier

31722152

Citation

Hatemi G, Mahr A, Ishigatsubo Y, Song YW, Takeno M, Kim D, Melikoglu M, Cheng S, McCue S, Paris M, Chen M, Yazici Y. Trial of Apremilast for Oral Ulcers in Behcet's Syndrome. N Engl J Med. 2019 Nov 14;381(20):1918-1928. doi: 10.1056/NEJMoa1816594.

Results Reference

derived

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

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

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

Behçet's Syndrome

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial