Clinical trial NCT03816891: Study to Assess the Efficacy, Safety, and Tolerability of Vixarelimab in Reducing Pruritus in Prurigo Nodularis
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prurigo Nodularis
Pruritis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Kiniksa Pharmaceuticals, Ltd.
First posted: 2019-01-25
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 2a: 2 arms; Phase 2b: 5 arms (4 arms during Double Blind Period and 1 arm during Open Label Extension)
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 2a & 2b: Percent Change From Baseline in Worst Itch Numeric Rating Scale (WI-NRS)
timeFrame: at Week 8 (Phase 2a); at Week 16 (Phase 2b)
Secondary outcomes:
measure: Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS at Week 8
timeFrame: Baseline, Week 8
measure: Phase 2a: Percent Change From Baseline in Pruritus Visual Analog Scale (VAS) at Week 8
timeFrame: Baseline, Week 8
measure: Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time
timeFrame: 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
measure: Phase 2a: Percent Change From Baseline in Weekly Average of WI-NRS Over Time
timeFrame: 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
measure: Phase 2a: Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 21, 22, 24
measure: Phase 2a: Percent Change From Baseline in Pruritis Visual Analog Scale (VAS) Over Time
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 21, 22, 24
measure: Phase 2a: Change From Baseline in 5-D Pruritus Total Score Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
measure: Phase 2a: Percent Change From Baseline in 5-D Pruritus Total Score Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
measure: Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS Over Time
timeFrame: 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
measure: Phase 2a: Change From Baseline in Sleep Loss VAS Over Time
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24
measure: Phase 2a: Percent Change From Baseline in Sleep Loss VAS Over Time
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24
measure: Phase 2a: Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time
timeFrame: 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
measure: Phase 2a: Percent Change From Baseline in Weekly Average of Difficulty Falling Asleep NRS Over Time
timeFrame: 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
measure: Phase 2a: Change From Baseline in Weekly Average of Sleep Quality NRS Over Time
timeFrame: 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
measure: Phase 2a: Percent Change From Baseline in Weekly Average of Sleep Quality NRS Over Time
timeFrame: 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
measure: Phase 2a: Change From Baseline in Quality of Life (QoL) Measure Dermatology QoL Index (DLQI) Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24
measure: Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24
measure: Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24
measure: Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24
measure: Phase 2a: Change From Baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) Over Time: Number of Nodules over the Whole Body Score
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
measure: Phase 2a: Change From Baseline in PN-NAT Over Time: Estimate of Hardness of Nodules Over the Whole Body
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
measure: Phase 2a: Change From Baseline in PN-NAT Over Time: Extent of Excoriations over the Whole Body
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
measure: Phase 2a: Percentage of Participants With Improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 Categories Over Time
timeFrame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24
measure: Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS at Week 16
timeFrame: Baseline, Week 16
measure: Phase 2b: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS at Week 16
timeFrame: Baseline, Week 16
measure: Phase 2b: Percentage of Participants Achieving a Score of 0 or 1 in PN-IGA at Week 16
timeFrame: Week 16
measure: Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time
timeFrame: Baseline, Weeks 1 through 52
measure: Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time
timeFrame: Baseline, Weeks 1 through 52
measure: Phase 2b: Percentage of Participants Achieving at Least a 6-Point Reduction From Baseline in Weekly Average WI-NRS Over Time
timeFrame: Baseline, Weeks 1 through 52
measure: Phase 2b: Percentage of Participants Achieving at Least a 4-Point Reduction From Baseline in Weekly Average WI-NRS Over Time
timeFrame: Baseline, Weeks 1 through 52
measure: Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
measure: Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in PN-IGA Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
measure: 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
timeFrame: Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
measure: Phase 2b: Percentage of Participants With at Least 2-Point Improvement From Baseline in IGA-CNPG-S Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
measure: Phase 2b: Change From Baseline in Weekly Average of Sleep Loss VAS Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
measure: Phase 2b: Percent Change From Baseline in Weekly Average of Sleep Loss VAS Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52
measure: Phase 2b: Change From Baseline in ItchyQoL Over Time
timeFrame: Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52
measure: Phase 2b: Percent Change From Baseline in ItchyQoL Over Time
timeFrame: Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Scottsdale
country: United States
facility: Investigate MD, LLC
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Fremont
country: United States
facility: Center for Dermatology Clinical Research, Inc.
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Los Angeles
country: United States
facility: Wallace Medical Group, Inc.
state: California
city: North Hollywood
country: United States
facility: Velocity Clinical Research - North Hollywood
state: California
city: Centennial
country: United States
facility: Colorado Center for Dermatology, PLLC
state: Colorado
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Rybear, Inc.
state: Florida
city: Gainesville
country: United States
facility: University of Florida, Department of Dermatology
state: Florida
city: Largo
country: United States
facility: Olympian Clinical Research
state: Florida
city: Miami
country: United States
facility: University of Miami Itch Center
state: Florida
city: Pembroke Pines
country: United States
facility: Riverchase Dermatology
state: Florida
city: Saint Petersburg
country: United States
facility: Olympian Clinical Research
state: Florida
city: Tampa
country: United States
facility: Advanced Clinical Research Institute
state: Florida
city: Tampa
country: United States
facility: Palm Harbor Dermatology
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research of Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Integrated Clinical Research
state: Florida
city: Sandy Springs
country: United States
facility: Advanced Medical Research PC
state: Georgia
city: New Albany
country: United States
facility: DS Research
state: Indiana
city: Louisville
country: United States
facility: DS Research
state: Kentucky
city: Beverly
country: United States
facility: ALLCUTIS Research, LLC
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices & Research, Inc.
state: Massachusetts
city: Clinton Township
country: United States
facility: Michigan Center for Skin Care Research
state: Michigan
city: Fort Gratiot
country: United States
facility: Hamzavi Dermatology
state: Michigan
city: Troy
country: United States
facility: Somerset Skin Centre
state: Michigan
city: Warren
country: United States
facility: Grekin Skin Institute
state: Michigan
city: Omaha
country: United States
facility: Skin Specialists, PC
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Bobby Buka MD, PC
state: New York
city: Rochester
country: United States
facility: University of Rochester Dermatology at College Town
state: New York
city: Fairborn
country: United States
facility: Wright State Physicians
state: Ohio
city: Philadelphia
country: United States
facility: Paddington Testing Co., Inc.
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Department of Dermatology and Dermatological Surgery
state: South Carolina
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research, Inc.
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research, PA
state: Texas
city: Spokane
country: United States
facility: Dermatology Specialists of Spokane
state: Washington
city: Kogarah
country: Australia
facility: Premier Specialists Pty Ltd
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Dermatology & Skin Cancer Centre
state: New South Wales
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research
state: Queensland
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Graz
country: Austria
facility: Medical University of Graz
city: Wien
country: Austria
facility: Medical University of Vienna
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc (UCL St-Luc)
city: Liège
country: Belgium
facility: CHU de Liège
city: Edmonton
country: Canada
facility: Stratica Medical
state: Alberta
city: Edmonton
country: Canada
facility: Alberta DermaSurgery Centre
state: Alberta
city: Red Deer
country: Canada
facility: Central Alberta Research Clinic (CARe Clinic)
state: Alberta
city: Fredericton
country: Canada
facility: Brunswick Dermatology Center
state: New Brunswick
city: Barrie
country: Canada
facility: SimcoDerm Medical and Surgical Dermatology Center
state: Ontario
city: London
country: Canada
facility: DermEffects
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc.
state: Ontario
city: Saint-Jérôme
country: Canada
facility: Drc Angélique Gagné-Henley MD Inc.
state: Quebec
city: Pardubice
country: Czechia
facility: CCR Czech a.s.
city: Praha 10
country: Czechia
facility: CLINTRIAL s.r.o.
city: Bordeaux
country: France
facility: Hôpital Saint André - CHU de Bordeaux
city: Brest
country: France
facility: Hôpital Morvan - CHU Brest
city: Nantes
country: France
facility: CHU Nantes - Service de Dermatologie
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim
state: Niedersachsen
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld Rosenhöhe
state: NRW
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Erlangen
country: Germany
facility: Studienzentrale Entzündliche Hauterkrankungen
city: Göttingen
country: Germany
facility: George-August-Universität Göttingen
city: Münster
country: Germany
facility: University Hospital Muenster, Department of Dermatology
city: Tübingen
country: Germany
facility: Eberhard-Karls-University
city: Witten
country: Germany
facility: Hautarztpraxis Dr. Hoffmann
city: Catania
country: Italy
facility: A.O.U. Policlinico Vittorio Emanuele
state: Sicily
city: Brescia
country: Italy
facility: Asst Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
city: Incheon
country: Korea, Republic of
facility: The Catholic University of Korea, Incheon St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Kraków
country: Poland
facility: Grażyna Pulka Centrum Medyczne All-Med
city: Rzeszów
country: Poland
facility: Kliniczny Szpital Wojewódzki Nr 1 im. Fryderyka Chopina w Rzeszowie, Klinika Dermatologii
city: Wrocław
country: Poland
facility: Kyclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska
city: New Taipei City
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital, Ministry of Health and Welfare
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh at Little France
city: Leytonstone
country: United Kingdom
facility: Barts Health NHS Trust, Whipps Cross Hospital
city: Liverpool
country: United Kingdom
facility: Broadgreen Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: