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

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ClinicalTrials.gov Identifier: NCT01232283
Recruitment Status : Completed
First Posted : November 2, 2010
Results First Posted : November 5, 2014
Last Update Posted : January 4, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Plaque Psoriasis
Interventions: Drug: Apremilast
Drug: Placebo
Other: Topical or Phototherapy Therapy

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 46 study centers in 9 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were eligible who had moderate to severe plaque psoriasis.

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

Participant Flow for 4 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   Apremilast (Long-Term Extension Phase)   Placebo-Apremilast (Long-term Extension)
STARTED   275   138   0   0   0   0   0   0   0   0 
Received Apremilast   272 [1]   136 [1]   0   0   0   0   0   0   0   0 
COMPLETED   239   112   0   0   0   0   0   0   0   0 
NOT COMPLETED   36   26   0   0   0   0   0   0   0   0 
Adverse Event                12                8                0                0                0                0                0                0                0                0 
Lack of Efficacy                3                2                0                0                0                0                0                0                0                0 
Noncompliance with study drug                1                0                0                0                0                0                0                0                0                0 
Withdrawal by Subject                9                7                0                0                0                0                0                0                0                0 
Lost to Follow-up                6                6                0                0                0                0                0                0                0                0 
Protocol Violation                3                2                0                0                0                0                0                0                0                0 
Not specified                2                1                0                0                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   Apremilast (Long-Term Extension Phase)   Placebo-Apremilast (Long-term Extension)
STARTED   0   0   234 [1]   108 [2]   0   0   0   0   0   0 
COMPLETED   0   0   194   100   0   0   0   0   0   0 
NOT COMPLETED   0   0   40   8   0   0   0   0   0   0 
Adverse Event                0                0                8                2                0                0                0                0                0                0 
Lack of Efficacy                0                0                19                3                0                0                0                0                0                0 
Non-compliance with study drug                0                0                1                0                0                0                0                0                0                0 
Withdrawal by Subject                0                0                7                1                0                0                0                0                0                0 
Lost to Follow-up                0                0                3                2                0                0                0                0                0                0 
Other                0                0                2                0                0                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   Apremilast (Long-Term Extension Phase)   Placebo-Apremilast (Long-term Extension)
STARTED   0   0   0   0   62 [1]   61 [2]   58   96   0   0 
Treated With APR+ Topicals/Phototherapy   0   0   0   0   0   0   28   17   0   0 
COMPLETED   0   0   0   0   50   56   41   84   0   0 
NOT COMPLETED   0   0   0   0   12   5   17   12   0   0 
Adverse Event                0                0                0                0                2                1                0                1                0                0 
Lack of Efficacy                0                0                0                0                4                0                13                5                0                0 
Withdrawal by Subject                0                0                0                0                3                3                3                4                0                0 
Death                0                0                0                0                1                0                0                0                0                0 
Lost to Follow-up                0                0                0                0                2                0                1                1                0                0 
Protocol Violation                0                0                0                0                0                0                0                1                0                0 
Other                0                0                0                0                0                1                0                0                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

Period 4:   Long-Term Extension Phase (Weeks 52-260)
    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   Apremilast (Long-Term Extension Phase)   Placebo-Apremilast (Long-term Extension)
STARTED   0   0   0   0   0   0   0   0   137   80 
COMPLETED   0   0   0   0   0   0   0   0   29   19 
NOT COMPLETED   0   0   0   0   0   0   0   0   108   61 
Adverse Event                0                0                0                0                0                0                0                0                11                6 
Lack of Efficacy                0                0                0                0                0                0                0                0                46                30 
Non-compliance                0                0                0                0                0                0                0                0                3                2 
Withdrawal by Subject                0                0                0                0                0                0                0                0                30                14 
Lost to Follow-up                0                0                0                0                0                0                0                0                9                6 
Death                0                0                0                0                0                0                0                0                1                0 
Protocol Violation                0                0                0                0                0                0                0                0                1                0 
Miscellaneous                0                0                0                0                0                0                0                0                7                3 



  Baseline Characteristics

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 
Overall Participants Analyzed 
[Units: Participants]
 274   137   411 
Age 
[Units: Years]
Mean (Standard Deviation)
 45.3  (13.05)   45.7  (13.38)   45.4  (13.15) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      98  35.8%      37  27.0%      135  32.8% 
Male      176  64.2%      100  73.0%      276  67.2% 
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

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 Treatment Emergent Adverse Events (TEAEs) 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 ]

13.  Secondary:   Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260   [ Time Frame: Week 0 to Week 260; The mean duration of exposure was 100.66 weeks. ]

14.  Secondary:   Number of Participants With Psoriasis Flare or Rebound in the Apremilast-Exposure Period   [ Time Frame: Week 0 to Week 260 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information

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



Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01232283     History of Changes
Other Study ID Numbers: CC-10004-PSOR-009
First Submitted: October 29, 2010
First Posted: November 2, 2010
Results First Submitted: October 22, 2014
Results First Posted: November 5, 2014
Last Update Posted: January 4, 2018