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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 Behcet's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT02307513
First received: December 2, 2014
Last updated: December 28, 2016
Last verified: December 2016
  Purpose

Behcet's disease, is a rare disorder that causes inflammation in blood vessels throughout the body. The signs and symptoms of Behcet'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 Behcet'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 test whether 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.

This study is a randomized, placebo-controlled, parallel design. About 204 subjects will participate. The placebo-controlled period will be 12 weeks long and patients will receive apremilast or placebo. After the 12-week placebo-controlled period, all subjects will receive apremilast for 1 year. All subjects will have their final study visit 4 weeks after stopping apremilast treatment.


Condition Intervention Phase
Behcet Syndrome
Drug: Apremilast (CC-10004)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Oral Ulcers [ Time Frame: 12 Weeks ]
    Area under the curve (AUC) for the number of oral ulcers from baseline through Week 12


Secondary Outcome Measures:
  • Complete response rate for oral ulcers at week 12 [ Time Frame: 12 Weeks ]
    Complete response rate for oral ulcers at Week 12 A complete response is defined as the proportion of subjects who are oral ulcer- free.

  • Pain of Oral Ulcers [ Time Frame: 12 Weeks ]
    Change from baseline in the pain of oral ulcers as measured by Visual analogue scale (VAS) at Week 12

  • Complete response rate for genital ulcers [ Time Frame: 12 Weeks ]
    Complete response rate for genital ulcers at Week 12 for subjects who had genital ulcers at Baseline A complete response is defined as the proportion of subjects who are genital ulcer-free.

  • Pain of genital ulcers [ Time Frame: 12 Weeks ]
    Change from baseline in the pain of genital ulcers, as measured by VAS at Week 12 in subjects who had genital ulcers at baseline

  • Disease activity [ Time Frame: 12 Weeks ]
    Change from baseline in disease activity as measured by Behçet's Disease Current Activity scores (BD Current Activity Form) at Week 12

  • Behçet's Disease Quality of Life (QOL) Score [ Time Frame: 12 weeks ]
    Change from baseline in the BD QoL score at Week 12

  • Behçet's Syndrome Activity Score [ Time Frame: 12 Weeks ]
    Change from Baseline in Behçet's Syndrome Activity Score (BSAS) at Week 12

  • Time to complete response of oral ulcers [ Time Frame: 12 Weeks ]
    Time to oral ulcer resolution (complete response), ie, the first instance when a subject has a complete response, during the Placebo-controlled Treatment Phase

  • No oral ulcers [ Time Frame: 12 Weeks ]
    Proportion of subjects with no oral ulcers following complete response, ie, the first time when a subject has a complete response, during the Placebo-controlled Treatment Phase

  • Number of oral ulcers [ Time Frame: 12 Weeks ]
    Number of oral ulcers following loss of complete response, ie, the first instance when a subject has a reappearance of oral ulcers following a complete response, during the Placebo-controlled Treatment Phase

  • Time to recurrence of oral ulcers [ Time Frame: 12 Weeks ]
    Time to recurrence of oral ulcers following loss of complete response, ie, the first instance when a subject has a reappearance of oral ulcers following a complete response, during the Placebo-controlled Treatment Phase

  • Static Physician's Global Assessment (PGA) [ Time Frame: 12 Weeks ]
    Change from baseline in the total score of the Static Physician's Global Assessment (PGA) of skin lesions (acne-like lesions, folliculitis and erythema nodosum) of BD at Week 12 in subjects who had BD skin lesions at baseline

  • Complete response rate for oral ulcers at Week 6 [ Time Frame: 12 Weeks ]
    Proportion of subjects achieving an oral ulcer complete response (oral ulcer-free) by Week 6, after start of dosing, and who remain oral ulcer free for at least 6 additional weeks during the 12-week Placebo-controlled Treatment Phase

  • Adverse Events to Apremilast [ Time Frame: 64 Weeks ]
    Type, frequency, severity, and relationship of the AEs to apremilast

  • Number of subjects discontinue [ Time Frame: 64 Weeks ]
    Number of subjects who prematurely discontinue IP due to any AE

  • Clinically significant changes [ Time Frame: 64 Weeks ]
    Frequency of clinically significant changes in vital signs, and/or laboratory findings


Estimated Enrollment: 204
Study Start Date: December 2014
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo + Apremilast
Patients randomized to this arm will receive placebo tablets by mouth twice daily for the first twelve weeks followed by 52 weeks of 30 mg apremilast tablets twice daily by mouth
Drug: Apremilast (CC-10004)
Other Name: Otezla
Drug: Placebo
Experimental: Apremilast (CC-10004)
Patients randomized to this arm will receive 30 mg Apremilast (CC-10004) tablets twice daily by mouth for 64 weeks.
Drug: Apremilast (CC-10004)
Other Name: Otezla

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 Behçet's disease meeting the 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:

    a. at least 2 oral ulcers at Visit 2 (day of randomization), when Visit 2 occurs at least 14 days after Visit 1. OR b. 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 109/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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02307513

Contacts
Contact: Sandra Collazo 908 897 6544 scollazo@celgene.com

  Show 63 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Lilia Pineda, MD Celgene Corporation
  More Information

Additional Information:
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT02307513     History of Changes
Other Study ID Numbers: CC-10004-BCT-002 
Study First Received: December 2, 2014
Last Updated: December 28, 2016

Keywords provided by Celgene Corporation:
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
Thalidomide
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
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on February 24, 2017