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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Chronic Idiopathic Urticaria, Chronic Idiopathic Pruritus, Lichen Planus, Lichen Simplex Chronicus, Plaque Psoriasis

Intervention / Treatment
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* Drug: KPL-716
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 75 years 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 Moderate to severe pruritus 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 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: Use of prohibited medications within the indicated timeframe from Day 1 to the End of Study Is currently using medication known to cause pruritus Has any inflammatory, pruritic, and/or fibrotic skin condition other than the diagnosis that defines inclusion Laboratory abnormalities that fall outside the windows specified in the protocol at the Screening Visit Has an active infection, including skin infection 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KPL-716<br>Weekly for 8 weeks | Drug: KPL-716<br>* 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.<br>* Other names: vixarelimab;|
| Placebo Comparator: Placebo<br>Weekly for 8 weeks | Drug: Placebo<br>* Placebo dose administered via 2 SC injections within 30 minutes on Day 1. All subsequent doses of placebo administered via a single SC injection.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pruritus, chronic pruritus, moderate to severe