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

• ClinicalTrials.gov Identifier: NCT02307513
• Recruitment Status: Completed
• First Posted: December 4, 2014
• Results First Posted: September 11, 2019
• Last Update Posted: July 22, 2021
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

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).

Condition or disease	Intervention/treatment	Phase
Behçet's Syndrome	Drug: Apremilast; Drug: Placebo	Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 207 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 30, 2014
• Actual Primary Completion Date: September 25, 2017
• Actual Study Completion Date: July 17, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Placebo / Apremilast; 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.	Drug: Apremilast; Tablets for oral administration; Other Names: Otezla®; CC-10004; Drug: Placebo; Tablets for oral administration
Experimental: Apremilast; Participants randomized to this arm will receive 30 mg apremilast tablets twice daily by mouth for 64 weeks.	Drug: Apremilast; Tablets for oral administration; Other Names: Otezla®; CC-10004

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. Change From Baseline in Oral Ulcer Pain as Measured by Visual Analog Scale (VAS) at Week 12 [ Time Frame: Baseline to 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.

2. Change From Baseline in Disease Activity as Measured by Behçet's Syndrome Activity Score (BSAS) at Week 12 [ Time Frame: Baseline to 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.
3. 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 ]
   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.
4. 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 ]
   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.
5. 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 ]
   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.
6. 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 ]
   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.
7. Time to Oral Ulcer Resolution (Complete Response) [ Time Frame: Baseline to week 12 ]
   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.
8. Percentage of Participants Who Experienced an Oral Ulcer Complete Response at Week 12 [ Time Frame: Week 12 ]
   A complete response at week 12 was defined as participants who were oral ulcer free at week 12.
9. Change From Baseline in Behçet's Disease Quality of Life (BD Qol) Scores at Week 12 [ Time Frame: Baseline to 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.
10. Percentage of Participants Who Experienced a Complete Response For Genital Ulcers at Week 12 [ Time Frame: Week 12 ]
    A genital ulcer complete response at week 12 was defined as participants who were genital ulcer-free at week 12.
11. Percentage of Participants With no Oral Ulcers Following a Complete Response [ Time Frame: Baseline 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.
12. Time to Recurrence of Oral Ulcers Following Loss of Complete Response [ Time Frame: Baseline through 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.
13. Number of Oral Ulcers Following Loss of Complete Response Through Week 12 [ Time Frame: Baseline 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.
14. 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 ]

    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.

15. Change From Baseline in Genital Ulcer Pain as Measured by VAS Score at Week 12 [ Time Frame: Baseline to 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.
16. 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. ]

    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.

17. 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. ]

    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
2. Male and female subjects ≥ 18 years of age at the time of signing the informed consent document.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosed with Behcet's disease meeting th4 International Study Group (ISG) criteria,
5. Oral ulcers that occurred at least 3 times in the previous 12-month period, including oral ulcers at the screening visit.

6. 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.
7. Have prior treatment with at least 1 non-biologic Behçet's disease therapy, such as, but not limited to, topical corticosteroids, or systemic treatment.

8. 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.

9. 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:

1. 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.
2. 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)
3. Prior use of apremilast.
4. Use of any investigational medication within 4 weeks prior to Visit 2 or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer).
5. Current use of strong cytochrome P450 enzyme inducers (eg, rifampin, phenobarbital, carbamazepine, phenytoin)

6. 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
7. Having received intra-articular or parenteral corticosteroids within 6 weeks (42 days) prior to Visit 2 (Baseline Visit; day of randomization).
8. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
9. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
10. Inability to provide voluntary consent.
11. Pregnant women or breast feeding mothers.
12. Systemic or opportunistic fungal infection.
13. 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.
14. Clinically significant abnormality on chest radiograph.
15. Clinically significant abnormality on 12-lead electrocardiogram (ECG).
16. History of positive test for, or any clinical suspicion of, human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).

17. 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.
18. Any condition that confounds the ability to interpret data from the study.
19. Scheduled surgery or other interventions that would interrupt the subject's participation in the study.
20. 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).

Contacts and Locations

Locations

United States, Arizona

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, United States, 85032

United States, California

University of California Davis Medical Center

Sacramento, California, United States, 95816

United States, Florida

Millennium Research

Ormond Beach, Florida, United States, 32174

United States, Georgia

Arthritis and Rheumatology of Georgia

Atlanta, Georgia, United States, 30342

United States, Illinois

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States, 60611

United States, Michigan

Advanced Rheumatology

Lansing, Michigan, United States, 48910

Shores Rheumatology

Saint Clair Shores, Michigan, United States, 48081

United States, New Mexico

University of New Mexico

Albuquerque, New Mexico, United States, 87131

United States, New York

New York Methodist Hospital

Brooklyn, New York, United States, 11215

NYU Langone Medical Center

New York, New York, United States, 10016

United States, Pennsylvania

University of Pennsylvania Health Systems

Philadelphia, Pennsylvania, United States, 19104

France

Hopital de La Conception

Marseille Cedex 05, France, 13385

Pitié-Salpêtriere Hospital Paris

Paris, France, 75013

Hopital Cochin

Paris, France, 75014

Hospital Saint Louis

Paris, France, 75475

Germany

Charite Universitaetsmedizin Berlin

Berlin, Germany, 10107

Stadtisches Klinikum Dessau

Dessau, Germany, 06847

Asklepios Rheumazentrum Hamburg

Hamburg, Germany, 22763

Greece

Navy Hospital of Athens

Athens, Greece, 115 21

Athens General Hospital 'G Gennimatas'

Athens, Greece, 115 27

Laiko General Hospital of Athens

Athens, Greece, 11527

Ippokratio General Hospital of Thessaloniki

Thessaloniki, Greece, 54642

Israel

Bnai Zion Medical Center

Haifa, Israel, 31048

Rambam Health Care Campus

Haifa, Israel, 31096

Hadassah Medical Organization

Jerusalem, Israel, 91120

Rabin Medical Center

Petah Tikva, Israel, 49100

Chaim Sheba Medical Center

Ramat Gan, Israel, 52621

Italy

Azienda Ospedaliero Universitaria Careggi

Firenze, Italy, 50134

Azienda Ospedaliera Regionale San Carlo

Potenza/Matera, Italy, 85100

Arcispedale Santa Maria Nuova

Reggio Emilia, Italy, 42100

Japan

Medical Hospital of Tokyo Medical and Dental University

Bunkyo-ku, Tokyo, Japan, 113-8519

Nippon Medical School Hospital

Bunkyo-ku, Japan, 113-8602

St. Luke's International Hospital

Chuo-ku, Japan, 104-8560

Tokyo Metropolitan Tama Medical Center

Fuchu-shi, Japan, 183-8524

Japanese Red Cross Society Himeji Hospital

Himeji-shi, Japan, 670-8540

Saitama Medical University Hospital

Iruma-gun, Saitama, Japan, 350-0495

Teikyo University Hospital

Itabashi-ku, Japan, 173-8606

Nihon University Itabashi Hospital

Itabashi-ku, Japan, 173-8610

St Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, Japan, 216-8511

University of Occupational and Environmentall Health

Kitakyushu, Japan, 807-8556

Kagawa University Hospital

Miki-cho, Japan, 761-0793

Kitasato University Hospital

Sagamihara, Japan, 228-8555

Saga Medical School Hospital

Saga, Japan, 849-8501

Sapporo Medical University Hospital

Sapporo, Hokkaidô, Japan, 060-8543

Hokkaido University Hospital

Sapporo, Hokkaidô, Japan, 060-8648

Shimonoseki City Hospital

Shimonoseki, Japan, 750-8520

Tokyo Medical University Hospital

Shinjyuku-ku, Japan, 160-0023

Tomishiro Central Hospital

Tomigusuku-shi, Japan, 901-0243

Ehime University Hospital

Toon, Japan, 791-0295

Yokohama City University Hospital

Yokohama, Kanagawa, Japan, 213-8507

Korea, Republic of

Chungnam National University Hospital

Daejeon, Korea, Republic of, 302799

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 120-752

Konkuk University Hospital

Seoul, Korea, Republic of, 143-729

Ajou University Hospital

Suwon si, Korea, Republic of, 16499

Lebanon

Hotel Dieu de France

Beirut, Lebanon

Ain Wazein Hospital

El Chouf, Lebanon

American University of Beirut Medical Center

El Chouf, Lebanon

Turkey

Cukurova University Medical Faculty Balcali Hospital

Adana, Turkey, 01330

Eskisehir Osmangazi University

Eskisehir, Turkey, 26480

Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, Turkey, 34098

Marmara University Hospital

Istanbul, Turkey, 34899

Selcuk University Medical Faculty

Konya, Turkey, 42080

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

  Study Documents (Full-Text)

Documents provided by Amgen:

Study Protocol  [PDF] July 5, 2017

Statistical Analysis Plan  [PDF] August 25, 2017

More Information

Additional Information:

AmgenTrials clinical trials website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02307513
• Other Study ID Numbers: CC-10004-BCT-002; 2014-002108-25 ( EudraCT Number )
• First Posted: December 4, 2014
• Results First Posted: September 11, 2019
• Last Update Posted: July 22, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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.
• 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.
• URL: https://www.amgen.com/datasharing

Keywords provided by Amgen:

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

Additional relevant MeSH terms:

Behcet Syndrome; Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases; Skin Diseases, Vascular; Apremilast; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action