Study to Assess the Efficacy, Safety, and Tolerability of Vixarelimab in Reducing Pruritus in Prurigo Nodularis

A Phase 2a/b, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of KPL-716 in Reducing Pruritus in Subjects With Prurigo Nodularis

Study of the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of Vixarelimab (KPL-716) in subjects with prurigo nodularis (PN).

Study Overview

• Status: Completed
• Conditions: Prurigo Nodularis; Pruritis
• Intervention / Treatment: Drug: Placebo; Drug: Vixarelimab

Detailed Description

This is a Phase 2a/b randomized, double-blind, placebo-controlled study to investigate the efficacy, safety, tolerability, PK and immunogenicity of Vixarelimab administered subcutaneously (SC) in subjects with prurigo nodularis experiencing pruritus.

Phase 2a portion:

Forty-nine subjects with moderate to severe PN experiencing moderate to severe pruritus are treated in the Phase 2a portion of the study. At Baseline, subjects are randomized 1:1 to receive double-blind (DBL) vixarelimab or placebo: vixarelimab 720 mg loading dose followed by 360 mg every week; placebo loading dose followed by placebo every week. The treatment period is 8 weeks or 16 weeks (treatment duration was reduced from 16 weeks to 8 weeks in a protocol amendment [Protocol Version 3]).

Phase 2b portion:

The Phase 2b study consists of a 4-week Screening Period and a 16-week Double-Blind Period, followed by a 36-week Open-Label-Extension (OLE) Period. Approximately 180 subjects with PN, experiencing severe pruritus, are randomized (at 1:1:1:1 ratio) into one of 4 arms (3 active arms and one placebo arm). A total of 4 doses of study drug are administered during the Double-Blind Period to measure the efficacy, safety, and PK of Vixarelimab. After the Double-Blind Period, all subjects have the option to receive vixarelimab during the OLE Period to evaluate the long-term safety and PK.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Premier Specialists Pty Ltd
    • Kogarah, New South Wales, Australia, 2217
      • St. George Dermatology & Skin Cancer Centre
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Veracity Clinical Research
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Austria
  • Graz, Austria, 8036
    • Medical University of Graz
  • Vienna, Austria, 1090
    • Medical University of Vienna
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc (UCL St-Luc)
  • Liège, Belgium, 4000
    • CHU de Liège
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • Stratica Medical
    • Edmonton, Alberta, Canada, T6G 1C3
      • Alberta Dermasurgery Centre
    • Red Deer, Alberta, Canada, T4N6V7
      • Central Alberta Research Clinic (CARe Clinic)
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 1G9
      • Brunswick Dermatology Center
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • SimcoDerm Medical and Surgical Dermatology Center
    • London, Ontario, Canada, N6H 5L5
      • DermEffects
    • Markham, Ontario, Canada, L3P 1X2
      • Lynderm Research Inc.
  • Quebec
    • Saint-Jérôme, Quebec, Canada, J7Z 7E2
      • Drc Angélique Gagné-Henley MD Inc.
• Czechia
  • Pardubice, Czechia, 53 002
    • CCR Czech a.s.
  • Prague, Czechia, 10000
    • CLINTRIAL s.r.o.
• France
  • Bordeaux, France, 33075
    • Hopital Saint Andre - CHU de Bordeaux
  • Brest, France, 29609
    • Hôpital Morvan - CHU Brest
  • Nantes, France, 44093
    • CHU Nantes - Service de Dermatologie
• Germany
  • Dresden, Germany, 01307
    • University Hospital Dresden
  • Erlangen, Germany, 91054
    • Studienzentrale Entzündliche Hauterkrankungen
  • Göttingen, Germany, 37075
    • George-August-Universität Göttingen
  • Münster, Germany, 48149
    • University Hospital Muenster, Department of Dermatology
  • Tübingen, Germany, 72076
    • Eberhard-Karls-University
  • Witten, Germany, 58453
    • Hautarztpraxis Dr. Hoffmann
  • Lower Saxony
    • Bad Bentheim, Lower Saxony, Germany, 48455
      • Fachklinik Bad Bentheim
  • North Rhine-Westphalia
    • Bielefeld, North Rhine-Westphalia, Germany, 33647
      • Klinikum Bielefeld Rosenhöhe
• Italy
  • Brescia, Italy, 25123
    • Asst Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
  • Sicily
    • Catania, Sicily, Italy, 95123
      • A.O.U. Policlinico Vittorio Emanuele
• Poland
  • Krakow, Poland, 30-033
    • Grażyna Pulka Centrum Medyczne All-Med
  • Rzeszów, Poland, 35-055
    • Kliniczny Szpital Wojewódzki Nr 1 im. Fryderyka Chopina w Rzeszowie, Klinika Dermatologii
  • Wroclaw, Poland, 50-367
    • Kyclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska
• South Korea
  • Incheon, South Korea, 21431
    • The Catholic University of Korea, Incheon St. Mary's Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Taiwan
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University Shuang Ho Hospital, Ministry of Health and Welfare
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital
• United Kingdom
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh at Little France
  • Leytonstone, United Kingdom, E11 1NR
    • Barts Health NHS Trust, Whipps Cross Hospital
  • Liverpool, United Kingdom, L14 3AB
    • Broadgreen Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
    • Scottsdale, Arizona, United States, 85255
      • Investigate MD, LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology
    • Fremont, California, United States, 94538
      • Center for Dermatology Clinical Research, Inc.
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Los Angeles, California, United States, 90056
      • Wallace Medical Group, Inc.
    • North Hollywood, California, United States, 91606
      • Velocity Clinical Research - North Hollywood
  • Colorado
    • Centennial, Colorado, United States, 80111
      • Colorado Center for Dermatology, PLLC
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Rybear, Inc.
    • Gainesville, Florida, United States, 32610
      • University of Florida, Department of Dermatology
    • Largo, Florida, United States, 33770
      • Olympian Clinical Research
    • Miami, Florida, United States, 33136
      • University of Miami Itch Center
    • Pembroke Pines, Florida, United States, 33028
      • Riverchase Dermatology
    • St. Petersburg, Florida, United States, 33709
      • Olympian Clinical Research
    • Tampa, Florida, United States, 33614
      • Olympian Clinical Research
    • Tampa, Florida, United States, 33615
      • Alliance Clinical Research of Tampa
    • Tampa, Florida, United States, 33607
      • Advanced Clinical Research Institute
    • Tampa, Florida, United States, 33609
      • Palm Harbor Dermatology
    • West Palm Beach, Florida, United States, 33406
      • Integrated Clinical Research
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • Advanced Medical Research PC
  • Indiana
    • New Albany, Indiana, United States, 47150
      • DS Research
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • DS Research
  • Massachusetts
    • Beverly, Massachusetts, United States, 01915
      • Allcutis Research, Llc
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc.
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Michigan Center for Skin Care Research
    • Fort Gratiot, Michigan, United States, 48059
      • Hamzavi Dermatology
    • Troy, Michigan, United States, 48084
      • Somerset Skin Centre
    • Warren, Michigan, United States, 08088
      • Grekin Skin Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Skin Specialists, PC
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10012
      • Bobby Buka MD, PC
    • Rochester, New York, United States, 14620
      • University of Rochester Dermatology at College Town
  • Ohio
    • Fairborn, Ohio, United States, 45324
      • Wright State Physicians
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Co., Inc.
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina, Department of Dermatology and Dermatological Surgery
  • Texas
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research, Inc.
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research, PA
  • Washington
    • Spokane, Washington, United States, 99202
      • Dermatology Specialists of Spokane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (apply to both Phase 2a and Phase 2b unless otherwise specified):

1. Male or female aged 18 to 75 years (Phase 2a), 18 to 80 years (Phase 2b)
2. Have clinical diagnosis of prurigo nodularis for at least 6 months
3. Have at least 10 nodules (Phase 2a), 20 nodules (Phase 2b) at the Screening Visit and Day 1
4. Moderate to severe pruritus (Phase 2a); severe pruritus (Phase 2b)
5. Female subjects of childbearing potential must have a negative pregnancy test, be nonlactating, and having agreed to use a highly effective method of contraception, as specified in the protocol, from the Screening Visit until 16 weeks after final study drug administration
6. 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 (apply to both Phase 2a and Phase 2b unless otherwise specified):

1. Use of prohibited medications within the indicated timeframe from Day 1
2. Is currently using medication known to cause pruritus
3. Presence of any inflammatory, pruritic, and/or fibrotic skin condition other than moderate to severe prurigo nodularis or atopic dermatitis unless approved by the Sponsor
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 subject 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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Phase 2a - Placebo SC QW; Placebo loading dose followed by placebo weekly for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2)	Drug: Placebo; solution for injection
Experimental: Phase 2a - Vixarelimab 360 mg SC Weekly (QW); Vixarelimab 720 mg loading dose followed by 360 mg weekly for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2)	Drug: Vixarelimab; solution for injection; Other Names: KPL-716; RG6536
Experimental: Phase 2b - Vixarelimab 540 mg SC Every 4 Weeks (Q4W; DBL); Vixarelimab 540 mg SC, every 4 weeks (Q4W) for 16 weeks during Double Blind Period	Drug: Vixarelimab; solution for injection; Other Names: KPL-716; RG6536
Experimental: Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL); Vixarelimab 360 mg SC, every 4 weeks (Q4W) for 16 weeks during Double Blind Period	Drug: Vixarelimab; solution for injection; Other Names: KPL-716; RG6536
Experimental: Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL); Vixarelimab 120 mg SC, every 4 weeks (Q4W) for 16 weeks during Double Blind Period	Drug: Vixarelimab; solution for injection; Other Names: KPL-716; RG6536
Placebo Comparator: Phase 2b - Placebo SC, Q4W (DBL); Placebo SC, every 4 weeks (Q4W) for 16 weeks during Double Blind Period	Drug: Placebo; solution for injection
Experimental: Phase 2b - Vixarelimab 360 mg SC, Every 2 Weeks (Q2W; OLE); Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during Open Label Extension	Drug: Vixarelimab; solution for injection; Other Names: KPL-716; RG6536

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2a & 2b: Percent Change From Baseline in Weekly Average Worst Itch-Numeric Rating Scale (WI-NRS) Score	Participants rated pruritus daily on the Worst Itch [pruritis] Numeric Rating Scale (WI-NRS: 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	at Week 8 (Phase 2a); at Week 16 (Phase 2b)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2a: Change From Baseline in Sleep Loss VAS Over Time	Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness).	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24
Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time	Participants rate difficulty falling asleep daily on Numerical Rating Scale (0=no difficulty, 10=extremely difficult).	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time	QoL was assessed at designated visits and includes the DLQI whereby 0=no effect on quality of life; 30= extremely large effect on QoL.	Baseline, Weeks 2, 4, 6, 8, 12, 16, 24
Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time	QoL was assessed at designated visits and includes the DLQI whereby 0=no effect on quality of life; 30= extremely large effect on QoL.	Baseline, Weeks 2, 4, 6, 8, 12, 16, 24
Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) 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 2, 4, 6, 8, 12, 16, 24
Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body	PN-NAT, assessed at designated visits, is a novel exploratory tool for the evaluation of disease severity based on estimate of the number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriation over the whole body, distribution of nodules, exact number of nodules in the representative area. The first three components (number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriations over the whole body) were analyzed as secondary endpoints. For the Estimate of Hardness of Nodules Over the Whole Body score: 0=No nodules are hard; 1=Up to one-third of nodules are hard; 2=One-third to two-thirds of nodules are hard; and 3=More than two-thirds of nodules are hard. A higher score indicates worse disease.	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time	PN-IGA is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease).	Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS at Week 8	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).	Baseline, Week 8
Phase 2a: Percent Change From Baseline in Pruritus Visual Analog Scale (VAS) at Week 8	At every visit, participants rated the intensity of their average pruritus over previous 3 days on VAS 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis)	Baseline, Week 8
Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time	Participants rated intensity of their average pruritus over previous 3 days on VAS 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis)	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 24
Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time	Participants rated intensity of their average pruritus over previous 3 days on VAS 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 24
Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time	Administered every 2 visits, the 5-D Pruritus Scale evaluates pruritus in 5 domains: duration, degree, direction, disability and distribution. The scores from each domain are added together to obtain a total 5-D score ranging from 5 (no pruritus) to 25 (most severe pruritus).	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time	Administered every 2 visits, the 5-D Pruritus Scale evaluates pruritus in five domains: duration, degree, direction, disability and distribution. The scores from each domain are added together to obtain a total 5-D score ranging from 5 (no pruritus) to 25 (most severe pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time	Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24
Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time	Participants rate difficulty falling asleep daily on Numerical Rating Scale (0=no difficulty, 10=extremely difficult). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time	Participants rated daily sleep quality on Numerical Rating Scale (0=best possible sleep, 10=worst possible sleep).	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time	Participants rated daily sleep quality on Numerical Rating Scale (0=best possible sleep, 10=worst possible sleep). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL 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). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 2, 4, 6, 8, 12, 16, 24
Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules Over the Whole Body Score	PN-NAT, assessed at designated visits, is a novel exploratory tool for the evaluation of disease severity based on estimate of the number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriation over the whole body, distribution of nodules, exact number of nodules in the representative area. The first three components (number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriations over the whole body) were analyzed as secondary endpoints. For the Number of Nodules over the Whole Body score: 0=0 nodules; 1=1 to 9 nodules; 2=10 to 50 nodules; and 3=more than 50 nodules. A higher score indicates worse disease.	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations Over the Whole Body	PN-NAT, assessed at designated visits, is a novel exploratory tool for the evaluation of disease severity based on estimate of the number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriation over the whole body, distribution of nodules, exact number of nodules in the representative area. The first three components (number of nodules over the whole body, estimate of hardness of nodules over the whole body, estimate of extent of excoriations over the whole body) were analyzed as secondary endpoints. For the Extent of Excoriations over the Whole Body score: 0=No nodules are excoriated; 1=Up to one-third of nodules are excoriated; 2=One-third to two-thirds of nodules are excoriated; and 3=More than two-thirds of nodules are excoriated. A higher score indicates worse disease.	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time	PN-IGA, assessed at designated visits, is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the presence/absence of nodules and the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease).	Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS at Week 16	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (0=no pruritus; 10=worst imaginable pruritus).	Baseline, Week 16
Phase 2b: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS at Week 16	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (0=no pruritus; 10=worst imaginable pruritus).	Baseline, Week 16
Phase 2b: Percentage of Participants Achieving a Score of 0 or 1 in PN-IGA at Week 16	PN-IGA, assessed at designated visits, is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the presence/absence of nodules and the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease); 0 (clear) indicates no nodules and 1 (almost clear) indicates nodules are present, few of the nodules are moderately raised.	Week 16
Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 1 through 52
Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 1 through 52
Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).	Baseline, Weeks 1 through 52
Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time	Participants rated pruritus daily on the Worst Itch [pruritis]-Numeric Rating Scale (WI-NRS; 0=no pruritus; 10=worst imaginable pruritus).	Baseline, Weeks 1 through 52
Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time	PN-IGA is a novel exploratory tool for the overall investigator assessment of PN disease severity based on the presence/absence of nodules and the size of the nodules as defined by their elevation. The IGA utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe disease); 0 (clear) indicates no nodules and 1 (almost clear) indicates nodules are present, few of the nodules are moderately raised.	Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
Phase 2b: Percentage of Participants Achieving 0 (Clear) or 1 (Almost Clear) in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) Over Time	IGA-CNPG-S is a novel tool for the investigator assessment of PN disease severity based on the number of palpable nodules and utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe); 0 (clear) indicates no nodules and 1 (almost clear) indicates rare palpable pruriginous nodules (approximately 1-5 nodules). A score is assigned based on the appearance of the disease at the time of the evaluation without referring to the baseline state.	Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
Phase 2b: Percentage of Participants With at Least 2-point Improvement From Baseline in IGA-CNPG-S Over Time	IGA-CNPG-S, administered at designated visits, is a novel tool for the investigator assessment of PN disease severity based on the number of palpable nodules and utilizes a 5-point scale that ranges from 0 (clear) to 4 (severe). A score is assigned based on the appearance of the disease at the time of the evaluation without referring to the baseline state.	Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time	Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness). A score was set to missing after a participant received prohibited/rescue medication that potentially impact efficacy analyses prior to Week 16, and the participant's worst post baseline observation before the time of the medication usage was carried forward (WOCF) to impute missing endpoint value (for participants whose postbaseline values were all missing, the baseline was used to impute). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time	Participants rated intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness). A score was set to missing after a participant received prohibited/rescue medication that potentially impact efficacy analyses prior to Week 16, and the participant's worst post baseline observation before the time of the medication usage was carried forward (WOCF) to impute missing endpoint value (for participants whose postbaseline values were all missing, the baseline was used to impute). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
Phase 2b: Change From Baseline in ItchyQoL 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). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52
Phase 2b: Percent Change From Baseline in ItchyQoL 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). The least squares mean (LSM) and LSM difference were rounded up or down to the nearest single decimal place.	Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Kiniksa Pharmaceuticals, Ltd.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Publications and helpful links

General Publications

• Stander S, Yosipovitch G, Sofen H, Abramzon D, Galanter J, Wang S, Paolini JF. Vixarelimab in Patients With Prurigo Nodularis: A Randomized Clinical Trial. JAMA Dermatol. 2025 Dec 17. doi: 10.1001/jamadermatol.2025.4950. Online ahead of print.
• Ma DX, Neerumalla S, Baird A, Whitehead RA, Filip P, Tajudeen BA, Batra PS, Papagiannopoulos P. Impact of Obesity on the Structured Histopathology of Chronic Rhinosinusitis Patients. Laryngoscope. 2025 Oct 6. doi: 10.1002/lary.70177. Online ahead of print.
• Sofen H, Bissonnette R, Yosipovitch G, Silverberg JI, Tyring S, Loo WJ, Zook M, Lee M, Zou L, Jiang GL, Paolini JF. Efficacy and safety of vixarelimab, a human monoclonal oncostatin M receptor beta antibody, in moderate-to-severe prurigo nodularis: a randomised, double-blind, placebo-controlled, phase 2a study. EClinicalMedicine. 2023 Feb 3;57:101826. doi: 10.1016/j.eclinm.2023.101826. eCollection 2023 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): December 28, 2022
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: January 23, 2019
• First Submitted That Met QC Criteria: January 23, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Manifestations; Skin Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Pruritus
• Other Study ID Numbers: KPL-716-C201; GS45044 (Other Identifier: Genentech, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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.: No