Behçet's SyndromePhase 3NCT02307513
A Phase 3 Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Active Behçet's Disease
A Phase 3 study testing Apremilast in people with Behçet's Syndrome, run by Amgen at 63 sites in 10 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Behçet's Syndrome
- What is being tested?
- Apremilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 207 participants
- Where
- 63 sitesin 10 countries
- Study dates
- 30 Dec 2014to 17 Jul 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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 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).
Who cannot join
None listed.
Trial locations and contacts
63 sites in 10 countries.
63 sites in 10 countries
Japan20 sites
Nippon Medical School Hospital
Bunkyō City, 113-8602
Medical Hospital of Tokyo Medical and Dental University
Bunkyo-ku, Tokyo, 113-8519
St. Luke's International Hospital
Chūōku, 104-8560
Tokyo Metropolitan Tama Medical Center
Fuchu-shi, 183-8524
Japanese Red Cross Society Himeji Hospital
Himeji-shi, 670-8540
Saitama Medical University Hospital
Iruma-gun, Saitama, 350-0495
Teikyo University Hospital
Itabashi-ku, 173-8606
Nihon University Itabashi Hospital
Itabashi-ku, 173-8610
St Marianna University School of Medicine Hospital
Kawasaki, Kanagawa, 216-8511
University of Occupational and Environmentall Health
Kitakyushu, 807-8556
Kagawa University Hospital
Miki-cho, 761-0793
Saga Medical School Hospital
Saga, 849-8501
Kitasato University Hospital
Sagamihara, 228-8555
Sapporo Medical University Hospital
Sapporo, Hokkaidô, 060-8543
Hokkaido University Hospital
Sapporo, Hokkaidô, 060-8648
Shimonoseki City Hospital
Shimonoseki, 750-8520
Tokyo Medical University Hospital
Shinjyuku-ku, 160-0023
Tomishiro Central Hospital
Tomigusuku-shi, 901-0243
Ehime University Hospital
Tōon, 791-0295
Yokohama City University Hospital
Yokohama, Kanagawa, 213-8507
United States11 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Arthritis and Rheumatology of Georgia
Atlanta, Georgia, 30342
New York Methodist Hospital
Brooklyn, New York, 11215
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Advanced Rheumatology
Lansing, Michigan, 48910
NYU Langone Medical Center
New York, New York, 10016
Millennium Research
Ormond Beach, Florida, 32174
University of Pennsylvania Health Systems
Philadelphia, Pennsylvania, 19104
Arizona Arthritis and Rheumatology Research, PLLC
Phoenix, Arizona, 85032
University of California Davis Medical Center
Sacramento, California, 95816
Shores Rheumatology
Saint Clair Shores, Michigan, 48081
Israel5 sites
Bnai Zion Medical Center
Haifa, 31048
Rambam Health Care Campus
Haifa, 31096
Hadassah Medical Organization
Jerusalem, 91120
Rabin Medical Center
Petah Tikva, 49100
Chaim Sheba Medical Center
Ramat Gan, 52621
South Korea5 sites
Chungnam National University Hospital
Daejeon, 302799
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 120-752
Konkuk University Hospital
Seoul, 143-729
Ajou University Hospital
Suwon, 16499
Turkey (Türkiye)5 sites
Cukurova University Medical Faculty Balcali Hospital
Adana, 01330
Eskisehir Osmangazi University
Eskişehir, 26480
Istanbul Universitesi Cerrahpasa Tip Fakultesi
Istanbul, 34098
Marmara University Hospital
Istanbul, 34899
Selcuk University Medical Faculty
Konya, 42080
France4 sites
Hopital de La Conception
Marseille, 13385
Pitié-Salpêtriere Hospital Paris
Paris, 75013
Hopital Cochin
Paris, 75014
Hospital Saint Louis
Paris, 75475
Greece4 sites
Navy Hospital of Athens
Athens, 115 21
Athens General Hospital 'G Gennimatas'
Athens, 115 27
Laiko General Hospital of Athens
Athens, 11527
Ippokratio General Hospital of Thessaloniki
Thessaloniki, 54642
Germany3 sites
Charite Universitaetsmedizin Berlin
Berlin, 10107
Stadtisches Klinikum Dessau
Dessau, 06847
Asklepios Rheumazentrum Hamburg
Hamburg, 22763
Italy3 sites
Azienda Ospedaliero Universitaria Careggi
Florence, 50134
Azienda Ospedaliera Regionale San Carlo
Potenza/Matera, 85100
Arcispedale Santa Maria Nuova
Reggio Emilia, 42100
Lebanon3 sites
Hotel Dieu de France
Beirut
Ain Wazein Hospital
El Chouf
American University of Beirut Medical Center
El Chouf
About this study
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
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).
Read the 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.
- Conditions
- Behçet's Syndrome
- Being tested
- Apremilast, Placebo
- Keywords
- APREMILAST (CC-10004), CC-10004, Efficacy, Safety, Phase 3, Behçet's Disease
- Medical subject headings
- Behcet Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApremilastDrug
Also called Otezla®, CC-10004
Tablets for oral administration
PlaceboDrug
Tablets for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Placebo / Apremilast | Experimental | 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. Receives: Drug: Apremilast; Drug: Placebo |
| Apremilast | Experimental | Participants randomized to this arm will receive 30 mg apremilast tablets twice daily by mouth for 64 weeks. Receives: Drug: Apremilast |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Oral ulcers were assessed at weeks 0 (baseline), 1, 2, 4, 6, 8, 10, and 12 during the placebo-controlled period.
Secondary outcomes (17)
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.
Measured: Baseline to week 12
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.
Measured: Baseline to week 12
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.
Measured: Baseline to week 12
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
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 Patient's 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.
Measured: Baseline to 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.
Measured: Baseline to week 12
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.
Measured: Baseline to week 12
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.
Measured: Baseline to week 12
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.
Measured: 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.
Measured: Baseline to week 12
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.
Measured: 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.
Measured: Baseline 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.
Measured: Baseline through week 12
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.
Measured: Baseline to week 12
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.
Measured: Baseline to week 12
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.
Measured: Baseline to week 12
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.
Measured: 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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study start30 Dec 2014
- Primary completion25 Sep 2017
- Study completion17 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Behçet's SyndromeStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02307513
- Sponsor's protocol ID
- CC-10004-BCT-002
- Other IDs
- 2014-002108-25, 2014
- Status last verified
- Jul 2021
- First submitted
- 2 Dec 2014
- Last updated
- 22 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
- Expanded access
- Available
Publications
Mease PJ, Hatemi G, Paris M, Cheng S, Maes P, Zhang W, Shi R, Flower A, Picard H, Stein Gold L. Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behcet's Syndrome. Am J Clin Dermatol. 2023 Sep;24(5):809-820. doi: 10.1007/s40257-023-00783-7. Epub 2023 Jun 14.
PubMed 37316690Hatemi 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.
PubMed 35798511Hatemi 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.
PubMed 31722152
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02307513
- Acronym / sponsor ID
- CC-10004-BCT-002
- Conditions
- Behçet's Syndrome
- Keywords
- APREMILAST (CC-10004), CC-10004, Efficacy, Safety, Phase 3, Behçet's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 30 Dec 2014 (actual)
- Primary completion
- 25 Sep 2017 (actual)
- Study completion
- 17 Jul 2020 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Posted 11 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo / Apremilast | Experimental | Drug: Apremilast, Drug: PlaceboParticipants 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. |
| Apremilast | Experimental | Drug: ApremilastParticipants randomized to this arm will receive 30 mg apremilast tablets twice daily by mouth for 64 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (61 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApremilastAlso: Otezla®, CC-10004Tablets for oral administration | Drug | Apremilast, Placebo / Apremilast |
| PlaceboTablets for oral administration | Drug | Placebo / Apremilast |
Primary outcome
Area Under the Curve (AUC) for the Number of Oral Ulcers From Baseline Through Week 12 (AUC W0-12)
Time frame: Oral ulcers were assessed at weeks 0 (baseline), 1, 2, 4, 6, 8, 10, and 12 during the placebo-controlled period.
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.
17 secondary outcomes
Change From Baseline in Oral Ulcer Pain as Measured by Visual Analog Scale (VAS) at Week 12
Time frame: Baseline to week 12
Change From Baseline in Disease Activity as Measured by Behçet's Syndrome Activity Score (BSAS) at Week 12
Time frame: Baseline to week 12
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
Time frame: Baseline to week 12
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
Time frame: Baseline to 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
Time frame: Baseline to week 12
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
Time frame: Baseline to week 12
Time to Oral Ulcer Resolution (Complete Response)
Time frame: Baseline to week 12
Percentage of Participants Who Experienced an Oral Ulcer Complete Response at Week 12
Time frame: Week 12
Change From Baseline in Behçet's Disease Quality of Life (BD Qol) Scores at Week 12
Time frame: Baseline to week 12
Percentage of Participants Who Experienced a Complete Response For Genital Ulcers at Week 12
Time frame: Week 12
Percentage of Participants With no Oral Ulcers Following a Complete Response
Time frame: Baseline to week 12
Time to Recurrence of Oral Ulcers Following Loss of Complete Response
Time frame: Baseline through week 12
Number of Oral Ulcers Following Loss of Complete Response Through Week 12
Time frame: Baseline to week 12
Change From Baseline in the Total Score of the Static Physician's Global Assessment (PGA) of Skin Lesions of BD at Week 12
Time frame: Baseline to week 12
Change From Baseline in Genital Ulcer Pain as Measured by VAS Score at Week 12
Time frame: Baseline to week 12
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-controlled Treatment Period
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.
Number of Participants With TEAEs During the Apremilast-Exposure Period
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37316690Mease PJ, Hatemi G, Paris M, Cheng S, Maes P, Zhang W, Shi R, Flower A, Picard H, Stein Gold L. Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behcet's Syndrome. Am J Clin Dermatol. 2023 Sep;24(5):809-820. doi: 10.1007/s40257-023-00783-7. Epub 2023 Jun 14.
- Derived from this study: PubMed 35798511Hatemi 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.
- Derived from this study: PubMed 31722152Hatemi 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
63 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apremilast in people with Behçet's Syndrome, run by Amgen at 63 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 61 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 63 sites in Japan, United States, Israel, South Korea, Turkey (Türkiye) and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (AUC) for the Number of Oral Ulcers From Baseline Through Week 12 (AUC W0-12) (time frame: Oral ulcers were assessed at weeks 0 (baseline), 1, 2, 4, 6, 8, 10, and 12 during the placebo-controlled period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02307513, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2021.