A Study of Ixekizumab (LY2439821) in Participants in Japan With Generalized Pustular Psoriasis and Erythrodermic Psoriasis

A Multicenter, Open-Label, Post Marketing Clinical Trial to Evaluate the Efficacy And Safety Of Ixekizumab in Patients With Generalized Pustular Psoriasis and Erythrodermic Psoriasis

The reason for this study is to see if the study drug ixekizumab is safe and effective in participants with generalized pustular psoriasis and erythrodermic psoriasis.

Study Overview

• Status: Completed
• Conditions: Generalized Pustular Psoriasis; Erythrodermic Psoriasis
• Intervention / Treatment: Drug: Ixekizumab

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 545-8586
    • Osaka City University Medical School Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173 8606
      • Teikyo University Hospital
    • Minato-Ku, Tokyo, Japan, 105-8471
      • Jikei University School of Medicine
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Present with GPP or EP based on an investigator-confirmed diagnosis and meet the associated criteria

  • GPP: Meet the criteria for GPP set by Ministry of Health, Labour and Welfare (MHLW) at screening and baseline regardless of IL-36 mutation status.
  • EP: Diagnosed to have BSA ≥80% involvement (with inflammatory erythema) at screening and baseline.
• Candidates for phototherapy and/or systemic therapy
• Men must agree to use a reliable method of birth control during the study
• Women must agree to use birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment

Exclusion Criteria:

• History of drug-induced psoriasis
• Concurrent or recent use of any biologic agent
• Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to enrollment and during the study
• Have previously received ixekizumab
• Serious disorder or illness other than psoriasis
• Serious infection within the last 12 weeks
• Breastfeeding or nursing (lactating) women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ixekizumab; Induction Dosing Period: Participants received 160 milligrams (mg) ixekizumab subcutaneously (SC) as 2 injections at Week 0 followed by 80 mg ixekizumab SC as 1 injection at Week 2, 4, 6, 8 and 10. Maintenance Dosing Period: Participants with Global Improvement Score (GIS) = 1 at Week 12 are responders who will complete the study. Participants who are inadequate responders (GIS ≥2 at Week 12 and based on the investigators' discretion) will be administered 80 mg ixekizumab SC as 1 injection at Week 12, 14, 16, and 18 or until they achieve a GIS score of 1.

Drug: Ixekizumab; Administered SC; Other Names: LY2439821

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance Dosing Period: Number of Participants Who Improved Global Improvement Score (GIS) at Least 1 Point From Week 12 Through Week 20 and With ≤2 of GIS	GIS was assessed in the 4 grades by comparing the psoriatic findings: (1) resolved, (2) improved, (3) unchanged, or (4) worsened. The global improvement score was assessed based on the comparison of the psoriatic findings, Static Physician Global Assessment (sPGA), Psoriasis Area and Severity Index (PASI) score, and other evaluations with those at the baseline.	Week 12 through Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance Dosing Period: Number of Participants With GIS Grade 1: Resolved	GIS was assessed in the 4 grades by comparing the psoriatic findings: (1) resolved, (2) improved, (3) unchanged, or (4) worsened. The global improvement score was assessed based on the comparison of the psoriatic findings, Static Physician Global Assessment (sPGA), Psoriasis Area and Severity Index (PASI) score, and other evaluations with those at the baseline.	Week 20
Maintenance Dosing Period: Number of Participants With GIS Grade 2: Improved	GIS was assessed in the 4 grades by comparing the psoriatic findings: (1) resolved, (2) improved, (3) unchanged, or (4) worsened. The global improvement score was assessed based on the comparison of the psoriatic findings, Static Physician Global Assessment (sPGA), Psoriasis Area and Severity Index (PASI) score, and other evaluations with those at the baseline.	Week 20
Maintenance Dosing Period: Number of Participants With GIS Grade 3: Unchanged	GIS was assessed in the 4 grades by comparing the psoriatic findings: (1) resolved, (2) improved, (3) unchanged, or (4) worsened. The global improvement score was assessed based on the comparison of the psoriatic findings, Static Physician Global Assessment (sPGA), Psoriasis Area and Severity Index (PASI) score, and other evaluations with those at the baseline.	Week 20
Maintenance Dosing Period: Number of Participants With GIS Grade 4: Worsened	GIS was assessed in the 4 grades by comparing the psoriatic findings: (1) resolved, (2) improved, (3) unchanged, or (4) worsened. The global improvement score was assessed based on the comparison of the psoriatic findings, Static Physician Global Assessment (sPGA), Psoriasis Area and Severity Index (PASI) score, and other evaluations with those at the baseline.	Week 20
Maintenance Dosing Period: Number of Participants Who Achieved Static Physician Global Assessment (sPGA) of (0, 1)	The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA assessed as either 0 or 1 represents a clinically meaningful response of minimal plaque severity or complete resolution of psoriasis.	Week 20
Maintenance Dosing Period: Number of Participants Who Achieved at Least a 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score (PASI 75) Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score (PASI 75)	PASI combines assessments of the extent of body surface involvement in 4 regions (head & neck(h), trunk(t), arms(u), legs(l)) & severity of scaling (S), redness (R), & plaque induration/infiltration (thickness, T) in each region. Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 4 for severe involvement): 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe Fraction of total body surface area (BSA) affected is graded on a 0-6 scale (0 for no involvement to 6 for 90% - 100% involvement): 0 = 0% (clear), 1 = >0% to <10%, 2 = 10% to <30%, 3 = 30% to <50%, 4 = 50% to <70%, 5 = 70% to 90%, 6 = 90% to 100%. Overall score ranges from 0 (no psoriasis) to 72 (most severe disease).	Week 20
Maintenance Dosing Period: Change From Baseline in Psoriasis Scalp Severity Index (PSSI) in Participants With Scalp Involvement at Baseline	The scalp was assessed for erythema (redness), induration (hardness), and desquamation (shedding of skin) and percentage of area affected as follows: Erythema, Induration and Desquamation: 0 = Absent; = Slight; = Moderate; = Severe; = Severest Possible Percent of Scalp Involved: = <10%; = 10% - 29%; = 30% - 49%; = 50% - 69%; = 70% - 89%; = 90% - 100% The PSSI score is a composite score derived from the sum of the scores for erythema, induration and desquamation multiplied by the score for the extent of scalp area involved (percent of scalp involved). The range is 0 (no psoriasis) to 72 (Most severe Disease).	Baseline, Week 20
Maintenance Dosing Period: Change From Baseline in Percent of Body Surface Area (BSA) Involvement of Psoriasis Body Surface Area (BSA) Involvement of Psoriasis	Percentage involvement of psoriasis on each participants body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including palm, fingers and thumb).	Baseline, Week 20
Maintenance Dosing Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score	The DLQI is a simple, patient-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all", "a little","a lot", and "very much", with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (the higher the score, the more quality of life is impaired) and a 5-point change from baseline is considered clinically relevant (Basra et al. 2008).	Baseline, Week 20
Maintenance Dosing Period: Number of Participants Who Developed Treatment-Emergent Anti-Ixekizumab Antibodies (TE-ADA)	Number of participants who developed treatment-emergent anti-ixekizumab antibodies (TE-ADA) was summarized by treatment group.	Week 20
Maintenance Dosing Period: Number of Participants Who Developed Neutralizing Anti-Ixekizumab Antibody (NAb)	Number of participants who developed neutralizing Anti-Ixekizumab antibody (NAb) was summarized by treatment group.	Week 20
Generalized Pustular Psoriasis (GPP) Only: Change From Baseline on Generalized Pustular Psoriasis Severity Index	GPP Severity Index was evaluated only for participants with pustular psoriasis at screening and at baseline. This is a composite score derived from the sum of scores for assessment of dermal symptoms, systemic symptoms, and laboratory findings (range, 0 to 17, with 17 representing severe symptoms). Skin symptoms were assessed by the score with the area of erythema (on a 0 to 3 scale), area of confluent pustules (on a 0 to 3 scale), and are of skin edema (on a 0 to 3 scale). The total score will be assessed (range, 0 to 9, with 9 representing severe symptoms). Systemic symptoms and laboratory findings were assessed by the score with fever (on a 0 to 2 scale), white blood cell (on a 0 to -2 scale), C-reactive protein (on a 0 to 2 scale) and Albumin (on a 0 to 2 scale). The total score will be assessed (range, 0 to 8, with 8 representing severe symptoms).	Baseline, Week 20

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Morita A, Okubo Y, Morisaki Y, Torisu-Itakura H, Umezawa Y. Ixekizumab 80 mg Every 2 Weeks Treatment Beyond Week 12 for Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis. Dermatol Ther (Heidelb). 2022 Feb;12(2):481-494. doi: 10.1007/s13555-021-00666-x. Epub 2021 Dec 29.

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2019
• Primary Completion (Actual): July 22, 2020
• Study Completion (Actual): July 22, 2020

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): August 13, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Japan; Generalized Pustular Psoriasis (GPP); Erythrodermic Psoriasis (EP)
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Dermatologic Agents; Ixekizumab
• Other Study ID Numbers: 17154; I1F-JE-RHCV (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes