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

NCT02307513 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-10004-BCT-0022014-002108-25
• Study Type: interventional
• Target: 207
• Locations: 10 countries
• Sites: 63

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).

Conditions

Behçet's Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Baseline to week 12

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

  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

  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

  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

  Baseline to week 12

Study Arms (2)

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.

Drug: Apremilast; Drug: Placebo

Apremilast

EXPERIMENTAL

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

Drug: Apremilast

Interventions

Apremilast DRUG

Tablets for oral administration

Also known as: Otezla®, CC-10004

Apremilast; Placebo / Apremilast

Placebo DRUG

Tablets for oral administration

Placebo / Apremilast

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (63)

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, 85032, United States

Location

University of California Davis Medical Center

Sacramento, California, 95816, United States

Location

Millennium Research

Ormond Beach, Florida, 32174, United States

Location

Arthritis and Rheumatology of Georgia

Atlanta, Georgia, 30342, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Advanced Rheumatology

Lansing, Michigan, 48910, United States

Location

Shores Rheumatology

Saint Clair Shores, Michigan, 48081, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

New York Methodist Hospital

Brooklyn, New York, 11215, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

University of Pennsylvania Health Systems

Philadelphia, Pennsylvania, 19104, United States

Location

Hopital de La Conception

Marseille, 13385, France

Location

Pitié-Salpêtriere Hospital Paris

Paris, 75013, France

Location

Hopital Cochin

Paris, 75014, France

Location

Hospital Saint Louis

Paris, 75475, France

Location

Charite Universitaetsmedizin Berlin

Berlin, 10107, Germany

Location

Stadtisches Klinikum Dessau

Dessau, 06847, Germany

Location

Asklepios Rheumazentrum Hamburg

Hamburg, 22763, Germany

Location

Navy Hospital of Athens

Athens, 115 21, Greece

Location

Athens General Hospital 'G Gennimatas'

Athens, 115 27, Greece

Location

Laiko General Hospital of Athens

Athens, 11527, Greece

Location

Ippokratio General Hospital of Thessaloniki

Thessaloniki, 54642, Greece

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Hadassah Medical Organization

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

Location

Azienda Ospedaliera Regionale San Carlo

Potenza/Matera, 85100, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, 42100, Italy

Location

Medical Hospital of Tokyo Medical and Dental University

Bunkyo-ku, Tokyo, 113-8519, Japan

Location

Nippon Medical School Hospital

Bunkyō City, 113-8602, Japan

Location

St. Luke's International Hospital

Chūōku, 104-8560, Japan

Location

Tokyo Metropolitan Tama Medical Center

Fuchu-shi, 183-8524, Japan

Location

Japanese Red Cross Society Himeji Hospital

Himeji-shi, 670-8540, Japan

Location

Saitama Medical University Hospital

Iruma-gun, Saitama, 350-0495, Japan

Location

Teikyo University Hospital

Itabashi-ku, 173-8606, Japan

Location

Nihon University Itabashi Hospital

Itabashi-ku, 173-8610, Japan

Location

St Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, 216-8511, Japan

Location

University of Occupational and Environmentall Health

Kitakyushu, 807-8556, Japan

Location

Kagawa University Hospital

Miki-cho, 761-0793, Japan

Location

Saga Medical School Hospital

Saga, 849-8501, Japan

Location

Kitasato University Hospital

Sagamihara, 228-8555, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaidô, 060-8543, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaidô, 060-8648, Japan

Location

Shimonoseki City Hospital

Shimonoseki, 750-8520, Japan

Location

Tokyo Medical University Hospital

Shinjyuku-ku, 160-0023, Japan

Location

Tomishiro Central Hospital

Tomigusuku-shi, 901-0243, Japan

Location

Ehime University Hospital

Tōon, 791-0295, Japan

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 213-8507, Japan

Location

Hotel Dieu de France

Beirut, Lebanon

Location

Ain Wazein Hospital

El Chouf, Lebanon

Location

American University of Beirut Medical Center

El Chouf, Lebanon

Location

Chungnam National University Hospital

Daejeon, 302799, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 120-752, South Korea

Location

Konkuk University Hospital

Seoul, 143-729, South Korea

Location

Ajou University Hospital

Suwon, 16499, South Korea

Location

Cukurova University Medical Faculty Balcali Hospital

Adana, 01330, Turkey (Türkiye)

Location

Eskisehir Osmangazi University

Eskişehir, 26480, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

Marmara University Hospital

Istanbul, 34899, Turkey (Türkiye)

Location

Selcuk University Medical Faculty

Konya, 42080, Turkey (Türkiye)

Location

Related Publications (3)

• 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.

  PMID: 37316690 DERIVED

• 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.

  PMID: 35798511 DERIVED

• 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.

  PMID: 31722152 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Behcet Syndrome

Interventions

apremilast

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vascular

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 4, 2014
• Study Start: December 30, 2014
• Primary Completion: September 25, 2017
• Study Completion: July 17, 2020
• Last Updated: July 22, 2021
• Results First Posted: September 11, 2019

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

GR (4); IL (5); IT (3); JP (20); TU (5); LE (3); FR (4); US (11); KR (5); DE (3)