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: January 29, 2015
Last verified: January 2015
Results First Received: October 22, 2014  
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
Condition: Plaque Psoriasis
Interventions: Drug: Apremilast
Drug: Placebo
Other: Topical or Phototherapy Therapy

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This is an ongoing study consisting of a 16-week randomized, double-blind, placebo-controlled phase, a 16-week randomized, double-blind active maintenance phase, a 20 week randomized treatment withdrawal phase and a 4-year open-label safety phase, for an overall study duration of 5 years. Data is reported up to Week 52.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Apremilast Participants initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)
Placebo Participants initially randomized to identically matching placebo tablets (PBO) BID during the Placebo controlled Phase (Weeks 0-16)
Apremilast-Apremilast Participants who were initially randomized to APR 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16) remained on APR 30 mg BID during the Maintenance Phase (Weeks 16-32).
Placebo-Apremilast Participants who were initially randomized to PBO BID during the Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to APR 30 mg BID and continued dosing with APR 30 mg BID during the Maintenance Phase (Weeks 16-32)
APR-APR-Re-randomized to PBO Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered responders (ie, having a ≥PASI-50 response) were re-randomized to PBO during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who lost ≥50% PASI improvement achieved at Week 32, were switched back to APR 30 mg BID at the time the loss was observed. Those participants who did not lose at least 50% of the PASI response remained on PBO until Week 52. All participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and received APR 30 mg BID for the remainder of their participation.
APR-APR Re-randomized to APR Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered responders (ie, having a ≥PASI-50 response) were re-randomized to APR during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and continued on APR 30 mg BID for the remainder of their participation.
APR-APR-APR + Optional Topicals/Phototherapy Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered non-responders (ie, having a response of <PASI-50), remained on APR 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and continued on APR 30 mg BID for the remainder of their participation.
PBO-APR-APR + Optional Topicals/Phototherapy Participants who were initially randomized to PBO BID during the 16-week Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to APR 30 mg BID and continued dosing with APR 30 mg BID during the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered non-responders (ie, having a response of <PASI-50), remained on APR 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. A subset of these partial or non-responders received additional topical or phototherapy. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and continued on APR 30 mg BID for the remainder of their participation.

Participant Flow for 3 periods

Period 1:   Placebo Controlled Phase (Weeks 0-16)
    Apremilast     Placebo     Apremilast-Apremilast     Placebo-Apremilast     APR-APR-Re-randomized to PBO     APR-APR Re-randomized to APR     APR-APR-APR + Optional Topicals/Phototherapy     PBO-APR-APR + Optional Topicals/Phototherapy  
STARTED     275     138     0     0     0     0     0     0  
Received Apremilast     272 [1]   136 [1]   0     0     0     0     0     0  
COMPLETED     239     112     0     0     0     0     0     0  
NOT COMPLETED     36     26     0     0     0     0     0     0  
Adverse Event                 12                 8                 0                 0                 0                 0                 0                 0  
Lack of Efficacy                 3                 2                 0                 0                 0                 0                 0                 0  
Noncompliance with study drug                 1                 0                 0                 0                 0                 0                 0                 0  
Withdrawal by Subject                 9                 7                 0                 0                 0                 0                 0                 0  
Lost to Follow-up                 6                 6                 0                 0                 0                 0                 0                 0  
Protocol Violation                 3                 2                 0                 0                 0                 0                 0                 0  
Not specified                 2                 1                 0                 0                 0                 0                 0                 0  
[1] 1 protocol violation occurred

Period 2:   Maintenance Phase (Weeks16-32)
    Apremilast     Placebo     Apremilast-Apremilast     Placebo-Apremilast     APR-APR-Re-randomized to PBO     APR-APR Re-randomized to APR     APR-APR-APR + Optional Topicals/Phototherapy     PBO-APR-APR + Optional Topicals/Phototherapy  
STARTED     0     0     234 [1]   108 [2]   0     0     0     0  
COMPLETED     0     0     194     100     0     0     0     0  
NOT COMPLETED     0     0     40     8     0     0     0     0  
Adverse Event                 0                 0                 8                 2                 0                 0                 0                 0  
Lack of Efficacy                 0                 0                 19                 3                 0                 0                 0                 0  
Non-compliance with study drug                 0                 0                 1                 0                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 7                 1                 0                 0                 0                 0  
Lost to Follow-up                 0                 0                 3                 2                 0                 0                 0                 0  
Unspecified                 0                 0                 2                 0                 0                 0                 0                 0  
[1] 5 participants discontinued after Week 16 but prior to entry into the Maintenance Phase
[2] 4 participants discontinued after Week 16 but prior to entry into the Maintenance Phase

Period 3:   Randomized Withdrawal Phase(Weeks 32-52)
    Apremilast     Placebo     Apremilast-Apremilast     Placebo-Apremilast     APR-APR-Re-randomized to PBO     APR-APR Re-randomized to APR     APR-APR-APR + Optional Topicals/Phototherapy     PBO-APR-APR + Optional Topicals/Phototherapy  
STARTED     0     0     0     0     62 [1]   61 [2]   58     96  
Treated With APR+ Topicals/Phototherapy     0     0     0     0     0     0     28     17  
COMPLETED     0     0     0     0     50     56     41     84  
NOT COMPLETED     0     0     0     0     12     5     17     12  
Adverse Event                 0                 0                 0                 0                 2                 1                 0                 1  
Lack of Efficacy                 0                 0                 0                 0                 4                 0                 13                 5  
Withdrawal by Subject                 0                 0                 0                 0                 3                 3                 3                 4  
Death                 0                 0                 0                 0                 1                 0                 0                 0  
Lost to Follow-up                 0                 0                 0                 0                 2                 0                 1                 1  
Protocol Violation                 0                 0                 0                 0                 0                 0                 0                 1  
Unspecified                 0                 0                 0                 0                 0                 1                 0                 0  
[1] 4 participants discontinued after Week 32 but prior to entry into the Randomized Withdrawal Phase
[2] 13 participants discontinued after Week 32 but prior to entry into the Randomized Withdrawal Phase



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set (FAS) consisted of all participants who were randomized as specified in the protocol. Those who were randomized in error and did not receive any dose of Investigational product (IP) were excluded from FAS. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS.

Reporting Groups
  Description
Apremilast Participants were initially randomized to Apremilast (APR) 30 mg tablets BID during the Placebo-controlled Phase (weeks 0-16)
Placebo Participants were initially randomized to placebo tablets BID during the Placebo controlled Phase (weeks 0-16).
Total Total of all reporting groups

Baseline Measures
    Apremilast     Placebo     Total  
Number of Participants  
[units: participants]
  274     137     411  
Age  
[units: years]
Mean (Standard Deviation)
  45.3  (13.05)     45.7  (13.38)     45.4  (13.15)  
Gender  
[units: participants]
     
Female     98     37     135  
Male     176     100     276  
Race/Ethnicity, Customized  
[units: participants]
     
American Indian or Alaska Native     1     1     2  
Asian     8     6     14  
Black or African American     13     2     15  
Native Hawaiian or Other Pacific Islander     1     0     1  
White     250     128     378  
Other-not specified     1     0     1  
Duration of Plaque Psoriasis [1]
[units: years]
Mean (Standard Deviation)
  17.94  (11.367)     18.68  (12.088)     18.19  (11.602)  
[1] All participants enrolled were required to have a diagnosis of plaque psoriasis at least 12 months prior to screening, but the duration was not required for enrollment. Overall baseline population for duration of plaque psoriasis in the apremilast arm were 271 participants and 135 for those in the placebo arm.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Who Achieved at Least a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 From Baseline   [ Time Frame: Baseline to Week 16 ]

2.  Secondary:   Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction From Baseline   [ Time Frame: Baseline to Week 16 ]

3.  Secondary:   Percent Change From Baseline in the Affected Body Surface Area (BSA) at Week 16   [ Time Frame: Baseline and Week 16 ]

4.  Secondary:   Percent Change From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 16   [ Time Frame: Baseline and Week 16 ]

5.  Secondary:   Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score (PASI-50) at Week 16 From Baseline   [ Time Frame: Baseline and Week 16 ]

6.  Secondary:   Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16   [ Time Frame: Baseline and Week 16 ]

7.  Secondary:   Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16   [ Time Frame: Baseline and Week 16 ]

8.  Secondary:   Change From Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16   [ Time Frame: Baseline to Week 16 ]

9.  Secondary:   Percentage of Participants Who Achieved Both a 75% Improvement (Response) in the PASI and sPGA Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction at Week 16 From Baseline   [ Time Frame: Baseline to Week 16 ]

10.  Secondary:   Time to 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: Weeks 32 to Week 52 ]

11.  Secondary:   Number of Participants With Adverse Events (AE) in the Placebo Controlled Phase   [ Time Frame: Baseline to Week 16 ]

12.  Secondary:   Number of Participants With Psoriasis Flare or Rebound in the Placebo Controlled Phase   [ Time Frame: Week 0 to Week 16 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain
Organization: Celgene Corporation
phone: 888-260-1599
e-mail: ClinicalTrialDisclosure@celgene.com


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
Results First Received: October 22, 2014
Last Updated: January 29, 2015
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