Clinical Trial: Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Efficacy of Oral Alitretinoin Treatment in Patients With Palmo-plantar Pustulosis (PPP) Inadequately Responding to Standard Topical Treatment

Brief Summary: The main purpose of this study is to demonstrate the improvement in the skin condition rate of patients receiving alitretinoin compared to patients receiving placebo.

Detailed Summary: Palmo-plantar pustulosis (PPP) is an inflammatory skin disease affecting palms and soles. The disease is considered as a sub-form of psoriasis and presents with sterile pustules of the palms and the soles. This study investigates the efficacy of alitretinoin in patients who have not responded to topical drugs (e.g., steroid creams), who are suffering for at least 6 month from the condition and whose disease severity is confirmed by a score.
Sponsor: Stiefel, a GSK Company

Current Primary Outcome:

  • Change From Baseline in the Palmo-plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) Score at the End of Treatment (EOT) (Week 24) or at the Last Assessment [ Time Frame: Baseline and EOT (Week 24) or the last assessment ]
    The investigator evaluated the PPPASI score on a 5-point scale. The parameters of erythema, total number of pustules, and desquamation were scored for the right/left palm and the right/left sole. After correcting the scores for area (based on a 7-point scale) and the site involved (palm or sole), the PPPASI score per palm/sole was produced. The final PPPASI score was calculated as the sum of the PPPASI score for the right sole + the PPPASI score for the left sole + the PPPASI score for the right palm + the PPPASI score for the left palm and ranges from 0 (no palmo-plantar pustulosis psoriasis [PPP]) to 72 (most severe PPP). Change from Baseline is defined as value at the EOT minus the Baseline value.
  • Number of Participants With PPPASI 50 Response and PPPASI 75 Response [ Time Frame: From Baseline until EOT (Week 24) or the last assessment ]
    The investigator evaluated the PPPASI score on a 5-point scale. The parameters of erythema, total number of pustules, and desquamation were scored for the right/left palm and the right/left sole. After correcting the scores for area (based on a 7-point scale) and the site involved (palm or sole), the PPPASI score per palm/sole was produced. The final PPPASI score was calculated as the sum of the PPPASI score for the right sole + the PPPASI score for the left sole + the PPPASI score for the right palm + the PPPASI score for the left palm and ranges from 0 (no palmo-plantar pustulosis psoriasis [PPP]) to 72 (most severe PPP). Change from Baseline is defined as valu

    Original Primary Outcome: Palmo-Plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) [ Time Frame: 24 weeks (End of Treatment) ]

    Scores for PPPASI will be obtained during screening, at baseline, at each visit during the treatment period and at EoT visit.


    Current Secondary Outcome:

    • Total Pustule Count at Baseline; Weeks 4, 8, 12, 16, and 20; and at EOT (Week 24) [ Time Frame: Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24) ]
      The overall number of fresh and older pustules on the left and right palms and soles was assessed at Baseline, at each visit during the treatment period (Weeks 4, 8, 12, 16, and 20), and at the EOT visit. The total pustule count was calculated as the sum of the pustule count for the left/right palm and left/right sole.
    • Absolute Change From Baseline (BL) in Total Pustule Count at Weeks 4, 8, 12, 16, and 20 and at EOT (Week 24) [ Time Frame: Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24) ]
      The overall number of fresh and older pustules on the left and right palms and soles was assessed at Baseline, at each visit during the treatment period (Weeks 4, 8, 12, 16, and 20), and at the End of Treatment visit. The total pustule count was calculated as the sum of the pustule count for the left/right palm and left/right sole. Change from Baseline is defined as the value at the post-Baseline visit minus the Baseline value.
    • Mean Modified Psoriasis Area Severity Index (mPASI) Score at Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24) [ Time Frame: Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24) ]
      Psoriatic plaques were graded based on three criteria: redness (R), thickness (T), and scaliness (S). Severity was rated for each criterion on a 5-point scale (0=no involvement, up to 4=severe involvement). Fraction of the total surface area affected on the head, upper extremities, trunk, and lower extremities was graded on a 7-point scale (0=no involvement, up to 6=greater than 90% involvement). The four body regions were weighted to reflect their respective proportion of body surface area, and the composite mPASI score for all body regions was calculated based on the redness, thickness, and scaliness scores of plaques (0-4 each) for the head, upper extremities, trunk, and lower extremities and the area of psoriatic involvement score (0-6). The lowest possible mPASI score was zero and highest up to 72; Higher score values represents greater severity of psoriasis. mPASI scores were continuous, with 0.1 increments within these values.
    • Change From Baseline in the mPASI Score at EOT (Week 24) or at the Last Assessment [ Time Frame: Baseline and EOT (Week 24) or the last assessment ]
      Psoriatic plaques were graded based on three criteria: redness (R), thickness (T), and scaliness (S). Severity was rated for each criterion on a 5-point scale (0=no involvement, up to 4=severe involvement). Fraction of the total surface area affected on the head, upper extremities, trunk, and lower extremities was graded on a 7-point scale (0=no involvement, up to 6=greater than 90% involvement). The four body regions were weighted to reflect their respective proportion of body surface area, and the composite mPASI score for all body regions was calculated based on redness, thickness, and scaliness scores of plaques (0-4 each) for head, upper extremities, trunk, lower extremities and area of psoriatic involvement score (0-6). Lowest possible mPASI score was 0 and highest up to 72; Higher score values represents greater severity of psoriasis. mPASI scores were continuous, with 0.1 increments within these values. Change from Baseline is defined as the value at EOT minus baseline value.
    • Number of Participants With mPASI 50 Response and mPASI 75 Response [ Time Frame: From Baseline until EOT (Week 24) ]
      Psoriatic plaques were graded based on three criteria: redness (R), thickness (T), and scaliness (S). Severity was rated for each criterion on a 5-point scale (0=no involvement, up to 4=severe involvement). The fraction of the total surface area affected on the head, upper extremities, trunk, and lower extremities was graded on a 7-point scale (0=no involvement, up to 6=greater than 90% involvement). The four body regions were weighted to reflect their respective proportion of body surface area, and the composite mPASI score for all body regions was calculated. mPASI 50 response and mPASI 75 response is defined as a 50% and 75% decrease, respectively, in the mPASI score from Baseline.
    • Mean Nail Psoriasis Severity Index (NAPSI) Score for Nail Bed Psoriasis and Nail Matrix Psoriasis at Baseline, Week 12, and EOT (Week 24) [ Time Frame: Baseline, Week 12, and EOT (Week 24) ]
      The severity of nail lesions was assessed for all participants with psoriatic nail involvement by obtaining the NAPSI score. Scores were taken for fingernails only. No scores were taken for participants with traumatic or fungal changes in nails. The nail was divided into four quadrants, each of which was rated with a 0 or 1, based on the absence (0) or presence (1) of pathological signs resulting from involvement of both the nail matrix and the nail bed. Each nail was given a score for nail bed psoriasis (0-4) and nail matrix psoriasis (0-4) depending on the presence of nail psoriasis in that quadrant. Possible scores for matrix and nail bed psoriasis: 0=none, 1=present in 1/4 nail, 2=present in 2/4 nail, 3=present in 3/4 nail, 4=present in 4/4 nail. NAPSI score for nail matrix (0-4) and nail bed (0-4) were reported at Baseline, Week 12, and at the EOT visit (Week 24).
    • Absolute Change From Baseline in NAPSI Score

      Original Secondary Outcome:

      • To assess the response of pustular lesions to total pustule count [ Time Frame: Day 1 to week 24 ]
        Pustule count will be performed at baseline, during treatment period and at EoT visit.
      • To assess the response to psoriasis lesions in locations other than the hands to the treatment [ Time Frame: Day 1 to week 24 ]
        mPASI
      • To assess the response of nail involvement to the treatment [ Time Frame: Day 1, week 12 and week 24 ]
        NAPSI Scores will be taken for finger nails only. No scores will be taken for patients with traumatic or fungal changes in nails (confirmed by KOH-test).
      • Safety [ Time Frame: Screening to End-of-study ]
        The investigator will evaluate safety in accordance with the Schedule of Assessments, by AE monitoring, laboratory tests (fasted lipid tests), physical examination, pregnancy testing for female patients of child bearing potential and the CES-D questionnaire.


      Information By: GlaxoSmithKline

      Dates:
      Date Received: November 16, 2010
      Date Started: April 2011
      Date Completion:
      Last Updated: February 17, 2017
      Last Verified: December 2016