Study to Evaluate Safety and Effectiveness of Oral Apremilast (CC-10004) in Patients With Moderate to Severe Plaque Psoriasis. (ESTEEM 2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01232283
First received: October 29, 2010
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

This study will evaluate the effects of an experimental (being tested) study drug called apremilast. Apremilast works by lowering some of the chemicals that affect psoriasis and therefore improves the symptoms of psoriasis. The purpose of this study is to test apremilast and compare its effects to placebo (an inactive substance which contains no medicine but is in the same form as the drug). This study will test efficacy (improvement of signs and symptoms) and safety of apremilast in patients with moderate to severe psoriasis.


Condition Intervention Phase
Plaque Psoriasis
Drug: Apremilast
Drug: Placebo
Other: Topical or Phototherapy Therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Proportion of subjects who achieve at least a 75% reduction in Psoriasis Area Severity Index (PASI-75) at Week 16 from baseline. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity.


Secondary Outcome Measures:
  • Proportion of subjects with a sPGA (static Physician Global Assessment) score of clear (0) or almost clear (1) with at least 2 points reduction from baseline at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]

    The sPGA is the assessment by the Investigator of the overall disease severity at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator should factor in areas that have already been cleared (ie, have scores of 0) and not just evaluate remaining lesions for severity, ie, the severity of each sign is averaged across all areas of involvement, including cleared lesions.

    In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score.


  • Body Surface Area BSA [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the subject's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area.

  • Percent change in the Psoriasis Area Severity Index (PASI) score from the Baseline Visit at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity.

  • Proportion of subjects who achieve PASI-50 at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity

  • Percent change from Baseline Pruritus VAS at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Change from baseline in Dermatology Life Quality Index (DLQI) total score at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    Dermatology Life Quality Index (DLQI) was developed as a practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. Higher scores correspond to poorer quality of life.

  • Change from baseline in Mental Component Summary (MCS) score of SF-36 at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    SF-36 is a 36-item general health status instrument often used in clinical trials and health services research. It consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH) (Ware, 1992). Scale scores range from 0 to 100, with higher scores indicating better health.

  • Proportion of subjects who achieve both PASI-75 and sPGA score of clear (0) or almost clear (1) with at least 2 points reduction from Baseline at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator should factor in areas that have already been cleared (ie, have scores of 0) and not just evaluate remaining lesions for severity, ie, the severity of each sign is averaged across all areas of involvement, including cleared lesions

  • Time to loss of loss of effect (loss of 50% improvement in PASI score obtained at Week 32 compared to baseline) during the Randomized Treatment Withdrawal Phase [ Time Frame: From Week 32 until approximately Week 52 ] [ Designated as safety issue: No ]
    : The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity.

  • Type, frequency, severity, seriousness, and relationship of adverse events to apremilast [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]
    Treatment Emergent Adverse events with a relationship to Apremilast

  • Number of subjects who prematurely discontinue Investigational Product due to an adverse event [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]

    At any time during the study, a subject may elect to withdraw from the study or the Investigator may discontinue a subject. The following events are considered sufficient reasons for discontinuing a subject from the investigational product and/or from the study:

    • Adverse event(s)
    • Lack of efficacy
    • Non-compliance with study drug
    • Withdrew consent
    • Study terminated by sponsor
    • Lost to follow-up
    • Death
    • Protocol violation

  • Frequency of clinically significant changes in physical examination, vital signs, electrocardiogram, and/or laboratory findings [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]
    Adverse events associated with clinically significant changes in physical examination, vital signs, electrocardiogram, and/or laboratory findings

  • Psoriasis flare or rebound [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]
    Psoriasis flare or rebound atypical or unusual worsening of disease during treatment; It is defined as a sudden intensification of psoriasis requiring medical intervention or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis.


Enrollment: 413
Study Start Date: November 2010
Estimated Study Completion Date: December 2016
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast
Participants will be initially randomized 2:1 to receive either apremilast 30 mg BID or identically matching placebo for 16 weeks. At week 16, placebo particpants will be switched to apremilast 30 mg BID for Weeks 16-32. Other Apremilast participants will maintain dosing through Week 32. At Week 32, responders (≥PASI-75) and partial responders (≥PASI-50) will be re-randomized 1:1 to apremilast 30 mg BID or matching placebo (treatment withdrawal). Placebo participants will resume apremilast 30mg BID at the time of loss of response compared to baseline), but no later than Week 52. At Week 32, the non-responders (< PASI-50) will have the option of adding topical therapies and/or phototherapy to their treatment regimen. Those re-randomized to Apremilast 30mg BID continue through week 52. At Week 52, all participants will continue treatment with apremilast 30 mg BID. Participants will be followed and evaluated for safety and efficacy for up to an additional 4 years (years 2 through 5).
Drug: Apremilast
Apremilast 30mg by mouth (PO) twice a day (BID) for 32 weeks
Other Names:
  • CC-10004
  • Otezla
Drug: Placebo
Identically matching placebo by mouth BID for first 16 weeks. Placebo participants will be switched to receive apremilast 30 mg BID at Week 16-32.
Other Name: Placebo
Other: Topical or Phototherapy Therapy
Topical or phototherapies are added for non-responders at Week 32, (< PASI-50) and added to their treatment regimen. The decision to add these treatments during this phase can only be made at the Week 32 visit.
Placebo Comparator: Placebo
Participants will be initially randomized to placebo, identically matching during Weeks 0-16. At Week 16, Placebo participants will be switched to receive apremilast 30 mg BID. All participants will maintain Apremilast dosing through Week 32. At Week 32, participants originally randomized to placebo at baseline (Week 0) and are considered non-responders i( < PASI-50) will have the option of adding topical therapies and/or phototherapy to their Apremilast treatment regimen. At Week 52, all participants will continue treatment with apremilast 30 mg BID. Participants will be followed and evaluated for safety and efficacy for up to an additional 4 years (years 2 through 5).
Drug: Apremilast
Apremilast 30mg by mouth (PO) twice a day (BID) for 32 weeks
Other Names:
  • CC-10004
  • Otezla
Drug: Placebo
Identically matching placebo by mouth BID for first 16 weeks. Placebo participants will be switched to receive apremilast 30 mg BID at Week 16-32.
Other Name: Placebo
Other: Topical or Phototherapy Therapy
Topical or phototherapies are added for non-responders at Week 32, (< PASI-50) and added to their treatment regimen. The decision to add these treatments during this phase can only be made at the Week 32 visit.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females, ≥ 18 years of age at the time of signing the informed consent document
  2. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening

    a. Have moderate to severe plaque psoriasis at Screening and Baseline

  3. Must meet all laboratory criteria
  4. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception as described by the Study Doctor while on study medication and for at least 28 days after taking the last dose of study medication
  5. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on study medication and for a least 28 days after the last dose of study medication.

Exclusion Criteria:

  1. Other than psoriasis, history of any clinically significant (as determined by the Investigator) or other major uncontrolled disease.
  2. Pregnant or breast feeding
  3. History of allergy to any component of the study drug
  4. Hepatitis B surface antigen positive at Screening
  5. Anti-hepatitis C antibody positive at Screening
  6. Active tuberculosis (TB) or a history of incompletely treated TB
  7. Clinically significant abnormality on 12-Lead ECG at Screening
  8. Clinically significant abnormal chest x-ray
  9. History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency
  10. Active substance abuse or a history of substance abuse within 6 months prior to Screening
  11. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening
  12. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years)
  13. Psoriasis flare or rebound within 4 weeks prior to Screening
  14. Evidence of skin conditions that would interfere with clinical assessments
  15. Topical therapy within 2 weeks of randomization
  16. Systemic therapy for psoriasis within 4 weeks prior to randomization
  17. Use of phototherapy within 4 weeks prior to randomization (ie, UVB, PUVA)
  18. Adalimumab, etanercept, infliximab, or certolizumab pegol within 12 weeks prior to randomization
  19. Alefacept, briakinumab, or ustekinumab within 24 weeks prior to randomization
  20. Use of any investigational drug within 4 weeks prior to randomization
  21. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources
  22. Prior treatment with apremilast
  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: NCT01232283

  Show 47 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Irina Khanskaya, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01232283     History of Changes
Other Study ID Numbers: CC-10004-PSOR-009
Study First Received: October 29, 2010
Last Updated: August 22, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Denmark: Danish Medicines Agency
Switzerland: Swissmedic
Austria: Agency for Health and Food Safety

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Apremilast
Thalidomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014