Efficacy and Safety of Etanercept 50 mg Once Weekly Plus As Needed Topical Agent in Moderate to Severe Plaque Psoriasis (REFINE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01313221
First received: February 24, 2011
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

To estimate the difference in effectiveness between treatment with etanercept 50 mg twice weekly (BIW) and treatment with etanercept 50 mg once weekly (QW) plus an as needed (PRN) topical agent for 12 weeks in adults with moderate to severe plaque psoriasis.


Condition Intervention Phase
Psoriasis
Biological: etanercept
Drug: Topical agents
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Blinded Assessor Study to Evaluate the Efficacy and Safety of Etanercept 50 mg Once Weekly Plus As Needed Topical Agent Versus Etanercept 50 mg Twice Weekly in Subjects With Moderate to Severe Plaque Psoriasis

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percent Change in Psoriasis Area and Severity Index (PASI) From Week 12 to Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
    The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from none (0), mild (1), moderate (2), severe (3) or very severe (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Change from Week 12 to Week 24 is presented as a percentage of the Week 12 value: Week 12 value - Week 24 value / Week 12 value * 100 so that a positive change indicates improvement. Change was adjusted for treatment using a mixed model.


Secondary Outcome Measures:
  • Percent Change in PASI From Week 12 to Weeks 16 and 20 [ Time Frame: Week 12, Week 16 and Week 20 ] [ Designated as safety issue: No ]
    The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from none (0), mild (1), moderate (2), severe (3) or very severe (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Change from Week 12 presented as a percentage of the Week 12 value: Week 12 value - postbaseline value / Week 12 value * 100, so that a positive change indicates improvement. Change was adjusted for treatment using a mixed model.

  • Percent Change in PASI From Baseline to Weeks 12, 16, 20, and 24 [ Time Frame: Baseline and Weeks 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from none (0), mild (1), moderate (2), severe (3) or very severe (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Change from Baseline is presented as a percentage of the Baseline value: Baseline value - postbaseline value / Baseline value * 100, so that a positive change indicates improvement.

  • Percentage of Participants With a PASI 50 Response [ Time Frame: Baseline and Weeks 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The percentage of participants with a 50% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination. The score ranges from 0 (best outcome) to 72 (worst outcome).

  • Percentage of Participants With a PASI 75 Response [ Time Frame: Baseline and Weeks 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The percentage of participants with a 75% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination. The score ranges from 0 (best outcome) to 72 (worst outcome).

  • Percentage of Participants With a PASI 90 Response [ Time Frame: Baseline and Weeks 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The percentage of participants with a 90% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination. The score ranges from 0 (best outcome) to 72 (worst outcome).

  • Percentage of Participants With a Static Physician's Global Assessment (sPGA) of Psoriasis Score of 0 (Clear) or 1 (Almost Clear) [ Time Frame: Weeks 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The sPGA scale is completed by the same blinded assessor performing the PASI assessments and is designed to evaluate the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale of 0 to 5 (0 = clear, 5 = severe).

  • Percent Change in the Percentage of Body Surface Area (BSA) Involvement From Week 12 to Weeks 16, 20, and 24 [ Time Frame: Weeks 12, 16, 20, and 24 ] [ Designated as safety issue: No ]

    The percentage of body surface area involved with psoriasis was measured by the same blinded assessor performing the PASI assessments. Change from Week 12 is presented as a percentage of the Week 12 value: Week 12 value - postbaseline value / Week 12 value * 100, so that a positive change indicates improvement.

    Change was adjusted for treatment using a mixed model.


  • Percent Change in the Percentage of Body Surface Area (BSA) Involvement From Baseline to Weeks 12, 16, 20, and 24 [ Time Frame: Baseline and Weeks 12, 16, 20, and 24 ] [ Designated as safety issue: No ]

    The percentage of body surface area involved with psoriasis was measured by the same blinded assessor performing the PASI assessments.

    Change from Baseline \ is presented as a percentage of the Baseline value: Baseline value - postbaseline value / Baseline value * 100, so that a positive change indicates improvement.


  • Change From Week 12 to Week 24 in Dermatology Quality of Life Index (DQLI) Total Score [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: No ]
    The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. Change from Week 12 to Week 24 is calculated as: Week 12 value - Week 24 value so that a positive change indicates improvement. Change was adjusted for treatment using a mixed model.

  • Change From Baseline to Weeks 12 and 24 in Dermatology Quality of Life Index (DQLI) Total Score [ Time Frame: Baseline and Week 12 and Week 24 ] [ Designated as safety issue: No ]
    The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. Change from Baseline was calculated as Baseline value - postbaseline value so that a positive change indicates improvement.

  • Change in Treatment Satisfaction Questionnaire for Medications (TSQM) Scores From Week 12 to Week 24 [ Time Frame: Week 12 and Week 24 ] [ Designated as safety issue: Yes ]
    TSQM is a validated questionnaire consisting of 14 questions regarding a participant's perception of the level of satisfaction or dissatisfaction with the medication they are taking. Four scales are generated: side effects, effectiveness, convenience, and global satisfaction. Optional responses are: Extremely Dissatisfied, Very Dissatisfied, Dissatisfied, Somewhat Satisfied, Satisfied, Very Satisfied, and Extremely Satisfied. From the responses, a scale score from 0 - 100 is calculated, with a higher score indicating greater satisfaction. Change was calculated as Week 24 - Week 12 so that a positive change indicates improvement over time. Change was adjusted for treatment using a mixed model.

  • Change in Treatment Satisfaction Questionnaire for Medications (TSQM) Scores From Baseline to Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: Yes ]
    The TSQM is a validated questionnaire consisting of 14 questions regarding a participant's perception of the level of satisfaction or dissatisfaction with the medication they are taking. Four scales are generated: side effects, effectiveness, convenience, and global satisfaction. Optional responses are: Extremely Dissatisfied, Very Dissatisfied, Dissatisfied, Somewhat Satisfied, Satisfied, Very Satisfied, and Extremely Satisfied. From the responses, a scale score from 0 - 100 is calculated, with a higher score indicating greater satisfaction. Change was calculated as postbaseline value - Baseline value so that a positive change indicates improvement.

  • Health Resource Utilization: Number of Participants With Visits to a Healthcare Provider [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants completed a questionnaire to assess their health resource utilization (HRU) related to psoriasis. To assess the number of visits to a healthcare provider, participants answered the following questions regarding the past 4 weeks: How many times have you been to any physician's office or urgent care clinic? How many times have you seen a nurse practitioner, a physician assistant, a psychologist, a naturopath, an acupuncturist, a chiropractor, or other healthcare professional (HCP)? The number of participants with one or more visits is reported.

  • Health Resource Utilization: Number of Participants With Home Healthcare Visits [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants completed a questionnaire to assess their health resource utilization (HRU) related to psoriasis. To assess the number of homecare visits, participants answered the following question regarding the past 4 weeks: How many times have you received care from a health professional in your home? The number of participants with one or more visits is reported.

  • Health Resource Utilization: Number of Participants Requiring Paid Help With Chores [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants completed a questionnaire to assess their health resource utilization (HRU) related to psoriasis. To assess the number of participants who needed paid help with chores, participants answered the following question regarding the past 4 weeks: How many times have you paid someone to help you do chores around the house (cleaning, maintenance, lawn care)? The number of participants who paid for help one or more times is reported.

  • Health Resource Utilization: Number of Participants Who Needed Friend or Family Care [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants completed a questionnaire to assess their health resource utilization (HRU) related to psoriasis. Participants answered the following question regarding the past 4 weeks: How many hours have you had a friend or family member take time off work to provide care or transportation? The number of participants who had paid or non-paid help for one or more hours is reported.

  • Health Resource Utilization: Out of Pocket Expenses [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants completed a questionnaire to assess their health resource utilization (HRU) related to psoriasis. To assess out of pocket expenses, participants answered the following question regarding the past 4 weeks: Not counting study mandated visits, what out-of-pocket expenses did you spend for the management of psoriasis (i.e. costs due to travelling to doctor appointment, hospital or clinic parking costs, alternative medications)?

  • Health Resource Utilization: Employment Status [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants completed a questionnaire to assess their health resource utilization (HRU) related to psoriasis. Participants were asked their employment status at Baseline and at Week 24.

  • Health Resource Utilization: Productivity While Working [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants who were employed were asked: How much did your psoriasis affect your productivity while you were working? Possible responses were: a) A great deal; b) Quite a bit; c) Somewhat; d) Minimally; e) Not at all.

  • Health Resource Utilization: Number of Participants With Missed Hours From Work [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants who were employed answered the following question regarding the past 4 weeks: How many hours per week did you miss from work because of your psoriasis? The number of participants with one or more missed hours of work per week is reported.

  • Health Resource Utilization: Ability to Perform Daily Activities [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Participants were asked: How much did your psoriasis affect your ability to do your daily activities or household chores? Possible answers were: a) A great deal; b) Quite a bit; c) Somewhat; d) Minimally; e) Not at all.

  • Number of Participants With Adverse Events [ Time Frame: 32 weeks ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal, • life threatening, • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other significant medical hazard.


Enrollment: 310
Study Start Date: April 2011
Study Completion Date: May 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Etanercept 50 mg BIW
Following 12 weeks of etanercept 50 mg twice weekly, participants were randomized to 50 mg etanercept twice weekly for 12 weeks.
Biological: etanercept
Administered by subcutaneous injection
Other Name: Enbrel
Experimental: Etanercept 50 mg QW + Topical
Following 12 weeks of etanercept 50 mg twice weekly, participants were randomized to 50 mg etanercept once weekly plus as needed topical agents.
Biological: etanercept
Administered by subcutaneous injection
Other Name: Enbrel
Drug: Topical agents

Topical agents prescribed at the discretion of the Principal Investigator and were are limited to the following:

  • hydrocortisone 2.5%
  • betamethasone valerate 0.1%
  • betamethasone dipropionate 0.05%
  • clobetasol 0.05%
  • calcitriol
  • calcipotriol plus betamethsone dipropionate 0.05%

Detailed Description:

The recommended starting dose of etanercept for adult plaque psoriasis patients is a 50 mg dose given twice a week (BIW) for 3 months followed by a reduction to a maintenance dose of 50 mg once weekly (QW). While most patients with moderate to severe plaque psoriasis are managed satisfactorily on etanercept monotherapy, a proportion may require a modified or alternative treatment regimen (eg, to handle flares or loss of effect) at some point during their chronic management. Despite the clinical need, no published data from randomized controlled studies are currently available that demonstrate efficacy and safety of combined etanercept-based regimens in patients with plaque psoriasis.

The addition of an as-needed topical medication to the step-down dose of etanercept 50 mg once weekly administered after the initial 12 week period of 50 mg twice weekly may be a potential option for patients who may require adjunctive therapy. This study aimed to provide data on this treatment option by estimating the difference in mean percent change in Psoriasis Area and Severity Index (PASI) scores between step-down etanercept 50 mg once weekly supplemented with as-needed topical medication and continuous treatment with etanercept 50 mg twice weekly.

Eligible patients will be enrolled in the study and will receive etanercept 50 mg twice weekly for 12 weeks. After 12 weeks of etanercept treatment, participants will be randomized in a 1:1 ratio to 1 of 2 treatment groups.

  Eligibility

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

Inclusion Criteria:

  • Has had stable moderate to severe plaque psoriasis for at least 6 months (eg, no morphology changes or significant flares of disease activity in the opinion of the investigator).
  • Has a body surface area (BSA) involvement ≥ 10% and Psoriasis Area and Severity Index (PASI) ≥ 10 at screening and at baseline.
  • Is a candidate for systemic therapy or phototherapy in the opinion of the investigator.
  • Other inclusion criteria may apply.

Exclusion Criteria:

  • Has active guttate, erythrodermic, or pustular psoriasis at the time of the screening visit.
  • Has evidence of skin conditions at the time of the screening visit (eg, eczema) that would interfere with evaluations of the effect of etanercept on psoriasis.
  • Diagnosed with medication-induced or medication-exacerbated psoriasis.
  • Significant concurrent medical conditions.
  • Has any active localized infection; requiring local intervention or chronic or localized infections.
  • Other exclusion criteria may apply.
  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: NCT01313221

Locations
Canada, Alberta
Research Site
Calgary, Alberta, Canada, T2G 1B1
Canada, British Columbia
Research Site
Surrey, British Columbia, Canada, V3R 6A7
Research Site
Vancouver, British Columbia, Canada, V5Z 4E8
Canada, Manitoba
Research Site
Winnipeg, Manitoba, Canada, R3C 0N2
Canada, New Brunswick
Research Site
Moncton, New Brunswick, Canada, E1C 8X3
Canada, Newfoundland and Labrador
Research Site
St. John's, Newfoundland and Labrador, Canada, A1C 2H5
Research Site
St. John's, Newfoundland and Labrador, Canada, A1A 5E8
Canada, Nova Scotia
Research Site
Halifax, Nova Scotia, Canada, B3H 1Z4
Canada, Ontario
Research Site
Courtice, Ontario, Canada, L1E 3C3
Research Site
Markham, Ontario, Canada, L3P 1A8
Research Site
Mississauga, Ontario, Canada, L5H 1G9
Research Site
North Bay, Ontario, Canada, P1B 3Z7
Research Site
Peterborough, Ontario, Canada, K9J 1Z2
Research Site
Richmond Hill, Ontario, Canada, L4B 1A5
Research Site
Sudbury, Ontario, Canada, P3C 1X8
Research Site
Toronto, Ontario, Canada, M3H 5Y8
Research Site
Toronto, Ontario, Canada, M4V 1R1
Research Site
Waterloo, Ontario, Canada, N2J 1C4
Research Site
Windsor, Ontario, Canada, N8W 5L7
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H2K 4L5
Research Site
Montreal, Quebec, Canada, H3Z 2S6
Research Site
Saint-Hyacinthe, Quebec, Canada, J2S 6L6
Canada
Research Site
Quebec, Canada, G1J 1X7
Research Site
Quebec, Canada, G1V 4X7
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01313221     History of Changes
Other Study ID Numbers: 20090647
Study First Received: February 24, 2011
Results First Received: December 10, 2013
Last Updated: May 20, 2014
Health Authority: Canada: Health Canada

Keywords provided by Amgen:
plaque psoriasis
moderate
severe
etanercept
Enbrel
topical

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
TNFR-Fc fusion protein
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
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 09, 2014