A Study to Assess the Efficacy, Safety, and Tolerability of KPL-716 in Reducing Pruritus in Chronic Pruritic Diseases

KPL-716-C202: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Pilot Study to Investigate the Efficacy, Safety, and Tolerability of KPL-716 in Reducing Pruritus in Diseases Characterized by Chronic Pruritus

Participants with diseases characterized by chronic pruritus experiencing moderate to severe pruritus will be enrolled in this pilot Phase 2 study.

The diseases characterized by chronic pruritus investigated in this pilot study currently include chronic idiopathic urticaria (CIU), chronic idiopathic pruritus (CIP), lichen planus (LP), lichen simplex chronicus (LSC) and plaque psoriasis (PPs).

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis; Chronic Idiopathic Urticaria; Lichen Planus; Lichen Simplex Chronicus; Chronic Idiopathic Pruritus
• Intervention / Treatment: Drug: KPL-716; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Site 106
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Site 110
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Site 114
  • California
    • Los Angeles, California, United States, 90045
      • Site 103
  • Florida
    • Clearwater, Florida, United States, 33756
      • Site 108
    • Gainesville, Florida, United States, 32610
      • Site 120
    • Sweetwater, Florida, United States, 33172
      • Site 113
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • Site 116
  • Illinois
    • Normal, Illinois, United States, 61761
      • Site 105
  • Indiana
    • Plainfield, Indiana, United States, 46168
      • Site 112
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Site 119
  • Michigan
    • Fort Gratiot, Michigan, United States, 48059
      • Site 109
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Site 121
  • New York
    • New York, New York, United States, 10012
      • Site 123
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Site 115
  • Texas
    • Houston, Texas, United States, 77004
      • Site 102
    • Pflugerville, Texas, United States, 78660
      • Site 104
    • San Antonio, Texas, United States, 78213
      • Site 101
  • Washington
    • Spokane, Washington, United States, 99202
      • Site 122

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged 18 to 75 years
2. Have clinical diagnosis of chronic idiopathic urticaria (CIU), chronic idiopathic pruritus (CIP), lichen planus (LP), lichen simplex chronicus (LSC) and plaque psoriasis (PPs) for at least 6 months
3. Moderate to severe pruritus
4. Female participants of childbearing potential must have a negative pregnancy test, be nonlactating, and have agreed to use a highly effective method of contraception, as specified in the protocol, from the Screening Visit until 10 weeks after final study drug administration
5. Able to comprehend and willing to sign an Informed Consent Form and able to abide by the study restrictions and comply with all study procedures for the duration of the study

Exclusion Criteria:

1. Use of prohibited medications within the indicated timeframe from Day 1 to the End of Study
2. Is currently using medication known to cause pruritus
3. Has any inflammatory, pruritic, and/or fibrotic skin condition other than the diagnosis that defines inclusion
4. Laboratory abnormalities that fall outside the windows specified in the protocol at the Screening Visit
5. Has an active infection, including skin infection
6. Any medical or psychiatric condition which, in the opinion of the Investigator or the Sponsor, may place the participant at increased risk as a result of study participation, interfere with study participation or study assessments, affect compliance with study requirements, or complicate interpretation of study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KPL-716; Weekly for 8 weeks	Drug: KPL-716; A loading dose of KPL-716 720 mg (2x maintenance dose) administered via 2 subcutaneous (SC) injections within 30 minutes on Day 1. All subsequent doses of KPL-716 (360 mg maintenance dose) administered via a single SC injection.; Other Names: vixarelimab
Placebo Comparator: Placebo; Weekly for 8 weeks	Drug: Placebo; Placebo dose administered via 2 SC injections within 30 minutes on Day 1. All subsequent doses of placebo administered via a single SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Average WI-NRS at Week 8	WI-NRS score: Participants were asked daily to assign a numerical score to the intensity of their most severe (worst) pruritus in the past 24 hours using a scale from 0 to 10, with 0 indicating no pruritus and 10 indicating the worst imaginable pruritus. Daily scores were averaged for a weekly score. A negative change from Baseline indicates improvement.	Baseline, Week 8
Percent Change From Baseline in Weekly Average WI-NRS at Week 8	WI-NRS score: Participants were asked daily to assign a numerical score to the intensity of their most severe (worst) pruritus in the past 24 hours using a scale from 0 to 10, with 0 indicating no pruritus and 10 indicating the worst imaginable pruritus. Daily scores were averaged for a weekly score. A negative change from Baseline indicates improvement.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Average WI-NRS Over Time	WI-NRS score: Participants were asked daily to assign a numerical score to the intensity of their most severe (worst) pruritus in the past 24 hours using a scale from 0 to 10, with 0 indicating no pruritus and 10 indicating the worst imaginable pruritus. Daily scores were averaged for a weekly score. A negative change from Baseline indicates improvement.	Baseline, Weeks 1-18
Percent Change From Baseline in Weekly Average WI-NRS Over Time	WI-NRS score: Participants were asked daily to assign a numerical score to the intensity of their most severe (worst) pruritus in the past 24 hours using a scale from 0 to 10, with 0 indicating no pruritus and 10 indicating the worst imaginable pruritus. Daily scores were averaged for a weekly score. A negative change from Baseline indicates improvement.	Baseline, Weeks 1-18
Change From Baseline in Pruritus Visual Analog Scale (VAS) Over Time	Participants were asked to place a line perpendicular to the VAS line at the point that represents the intensity of their average pruritus experienced over the previous 3 days using a scale from 0 to 10, with 0 indicating no pruritus and 10 indicating the worst imaginable pruritus.	Baseline, Weeks 1-8, 10, 12, 14, 16, 18
Percent Change From Baseline in Pruritus VAS Over Time	Participants were asked to place a line perpendicular to the VAS line at the point that represents the intensity of their average pruritus experienced over the previous 3 days using a scale from 0 to 10, with 0 indicating no pruritus and 10 indicating the worst imaginable pruritus.	Baseline, Weeks 1-8, 10, 12, 14, 16, 18
Change From Baseline in 5-D Pruritus Total Score Over Time	This tool evaluates pruritus in 5 domains: duration, degree, direction, disability and distribution. Duration, degree and direction each consist of 1 item. The disability domain contains 4 items and the distribution domain includes 16 items. The first 4 domains are measured on a 5-point Likert scale. The scores from each domain are added together to obtain a total 5-D score ranging from 5 (no pruritus) and 25 (most severe pruritus).	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18
Percent Change From Baseline in 5-D Pruritus Total Score Over Time	This tool evaluates pruritus in 5 domains: duration, degree, direction, disability and distribution. Duration, degree and direction each consist of 1 item. The disability domain contains 4 items and the distribution domain includes 16 items. The first 4 domains are measured on a 5-point Likert scale. The scores from each domain are added together to obtain a total 5-D score ranging from 5 (no pruritus) and 25 (most severe pruritus).	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18
Percentage of Participants Achieving ≥4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time	WI-NRS score: Participants were asked daily to assign a numerical score to the intensity of their most severe (worst) pruritus in the past 24 hours using a scale from 0 to 10, with 0 indicating no pruritus and 10 indicating the worst imaginable pruritus. Daily scores were averaged for a weekly score. A negative change from Baseline indicates improvement.	Baseline, Weeks 1-18
Change From Baseline in Weekly Average Itch Severity Score: CIU Cohort Only	Participants were asked daily to self-assess the intensity of their pruritus on a Weekly Average Itch Severity Score, which is a Component of Urticaria Activity Score 7 (UAS7). The score for pruritis was graded from 0 (none) to 3 (intense), which was averaged over 7 consecutive days. The greater the severity of the disease the higher the score. Per protocol, the UAS7 tool was completed only by participants in the CIU Cohort.	Baseline, Weeks 1-18
Percent Change From Baseline in Weekly Average Itch Severity Score: CIU Cohort Only	Participants were asked daily to self-assess the intensity of their pruritus on a Weekly Average Itch Severity Score, which is a Component of Urticaria Activity Score 7 (UAS7). The score for pruritis was graded from 0 (none) to 3 (intense), which was averaged over 7 consecutive days. The greater the severity of the disease the higher the score. Per protocol, the UAS7 tool was completed only by participants in the CIU Cohort	Baseline, Weeks 1-18
Change From Baseline in Sleep Loss VAS Over Time	Participants were asked to place a line perpendicular to the VAS line at the point that represents the intensity of their average sleeplessness experienced over the previous 3 nights using a scale from 0 to 10, with 0 indicating no sleeplessness and 10 indicating the worst imaginable sleeplessness at every visit.	Baseline, Weeks 1-8, 10, 12, 14, 16, 18
Percent Change From Baseline in Sleep Loss VAS Over Time	Participants were asked to place a line perpendicular to the VAS line at the point that represents the intensity of their average sleeplessness experienced over the previous 3 nights using a scale from 0 to 10, with 0 indicating no sleeplessness and 10 indicating the worst imaginable sleeplessness at every visit.	Baseline, Weeks 1-8, 10, 12, 14, 16, 18
Change From Baseline in Weekly Average of Difficulty Falling Asleep Numerical Rating Scale (NRS) Over Time	Participants were asked daily to assign a numerical score to the intensity of their difficulty falling asleep last night due to itch using a scale from 0 to 10, with 0 indicating not difficult at all and 10 indicating extremely difficult.	Baseline, Weeks 1-18
Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time	Participants were asked daily to assign a numerical score to the intensity of their difficulty falling asleep last night due to itch using a scale from 0 to 10, with 0 indicating not difficult at all and 10 indicating extremely difficult.	Baseline, Weeks 1-18
Change From Baseline in Weekly Average of Sleep Quality NRS Over Time	Participants were asked daily to assign a numerical score to the quality of their sleep in the previous night using a scale from 0 to 10, with 0 indicating best possible sleep and 10 indicating worst possible sleep.	Baseline, Weeks 1-18
Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time	Participants were asked daily to assign a numerical score to the quality of their sleep in the previous night using a scale from 0 to 10, with 0 indicating best possible sleep and 10 indicating worst possible sleep.	Baseline, Weeks 1-18
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score Over Time	The DLQI is a 10-question questionnaire that considers symptoms and feelings, daily activities, leisure, school, personal relationships, and treatment. Each question, except question 7, is answered on a scale of 0 to 3 (0 for not at all, 1 for a little, 2 for a lot, and 3 for very much), taking into account the previous week. For question 7: participants were asked "Over the last week, has your skin prevented you from working or studying?" If answered yes, score=3; If no, a second question will be asked: "Over the last week how much has your skin been a problem at work or studying?" If further answered a lot, score=2; if a little, score=1; if not at all or not relevant, score=0. The DLQI total score is defined as the sum of all 10-question scores with minimum of 0 meaning no effect on quality of life and 30 meaning extremely large effect.	Baseline, Weeks 4, 8, 12, 16, 18
Percent Change From Baseline in DLQI Total Score Over Time	The DLQI is a 10-question questionnaire that considers symptoms and feelings, daily activities, leisure, school, personal relationships, and treatment. Each question, except question 7, is answered on a scale of 0 to 3 (0 for not at all, 1 for a little, 2 for a lot, and 3 for very much), taking into account the previous week. For question 7: participants were asked "Over the last week, has your skin prevented you from working or studying?" If answered yes, score=3; If no, a second question will be asked: "Over the last week how much has your skin been a problem at work or studying?" If further answered a lot, score=2; if a little, score=1; if not at all or not relevant, score=0. The DLQI total score is defined as the sum of all 10-question scores with minimum of 0 meaning no effect on quality of life and 30 meaning extremely large effect.	Baseline, Weeks 4, 8, 12, 16, 18
Change From Baseline in ItchyQoL Total Score Over Time	ItchyQoL focuses on impact of pruritus on daily activities and on the level of psychological stress. It contains 22 items. The frequency items are scored using a 5-point Likert scale ranging from "never" to "all the time". The bother items are scored from 1 (not bothered) to 5 (severely bothered). The recall period in ItchyQoL is the past week. The ItchyQoL total score is defined as the sum of all 22-items scores. Total scores can be classified as little (0-30), mild (31-50), moderate (51-80), and severe (81-110).	Baseline, Weeks 4, 8, 12, 16, 18
Percent Change From Baseline in ItchyQoL Total Score Over Time	ItchyQoL focuses on impact of pruritus on daily activities and on the level of psychological stress. It contains 22 items. The frequency items are scored using a 5-point Likert scale ranging from "never" to "all the time". The bother items are scored from 1 (not bothered) to 5 (severely bothered). The recall period in ItchyQoL is the past week. The ItchyQoL total score is defined as the sum of all 22-items scores. Total scores can be classified as little (0-30), mild (31-50), moderate (51-80), and severe (81-110).	Baseline, Weeks 4, 8, 12, 16, 18

Collaborators and Investigators

• Sponsor: Kiniksa Pharmaceuticals, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2019
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): June 8, 2020

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Actual): December 28, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: pruritus, chronic pruritus, moderate to severe
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Skin Diseases, Papulosquamous; Hypersensitivity; Skin Manifestations; Dermatitis; Skin Diseases, Eczematous; Lichenoid Eruptions; Psoriasis; Pruritus; Urticaria; Chronic Urticaria; Lichen Planus; Neurodermatitis
• Other Study ID Numbers: KPL-716-C202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No