Study to Assess the Efficacy, Safety, and Tolerability of Vixarelimab in Reducing Pruritus in Prurigo Nodularis
- Registration Number
- NCT03816891
- Lead Sponsor
- Kiniksa Pharmaceuticals, Ltd.
- Brief Summary
Study of the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of Vixarelimab (KPL-716) in subjects with prurigo nodularis.
- 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 (completed):
Forty-nine subjects with moderate to severe PN experiencing moderate to severe pruritus were treated in the Phase 2a portion of the study. At Baseline, subjects were randomized 1:1 to receive double-blind 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 was 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 (enrolling):
The Phase 2b study (Figure 1) will consist 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, will be 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 will be administered during the Double-Blind Period to measure the efficacy, safety, and PK of Vixarelimab. After the Double-Blind Period, all subjects will have the option to receive Vixarelimab during the OLE Period to evaluate the long-term safety and PK.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 190
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 2a - Placebo SC QW Placebo Placebo loading dose followed by placebo weekly for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2) Phase 2a - Vixarelimab 360 mg SC QW vixarelimab Vixarelimab 720 mg loading dose followed by 360 mg weekly for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2) Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL) vixarelimab Vixarelimab 120 mg SC, every 4 weeks for 16 weeks during Double Blind Period Phase 2b - Placebo SC, Q4W (DBL) Placebo Placebo SC, every 4 weeks for 16 weeks during Double Blind Period Phase 2b - Vixarelimab 540 mg SC Q4W (DBL) vixarelimab Vixarelimab 540 mg SC, every 4 weeks for 16 weeks during Double Blind Period Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL) vixarelimab Vixarelimab 360 mg SC, every 4 weeks for 16 weeks during Double Blind Period Phase 2b - Vixarelimab 360 mg SC, Q2W (OLE) vixarelimab Vixarelimab 360 mg SC, every 2 weeks for 36 weeks during Open Label Extension
- Primary Outcome Measures
Name Time Method Phase 2a & 2b: Percent change from baseline in Worst Itch Numeric Rating Scale (WI-NRS) at Week 8 (Phase 2a); at Week 16 (Phase 2b) Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
- Secondary Outcome Measures
Name Time Method Phase 2a: Proportion of subjects achieving at least a 4-point reduction from baseline in weekly average WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) over time to end of treatment, assessed up to 24 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2a: Change from baseline in Sleep Loss VAS over time to end of treatment, assessed up to 24 weeks At every visit, subjects rate intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness)
Phase 2a: Percent change from baseline in weekly average of difficulty falling asleep NRS over time to end of treatment, assessed up to 24 weeks Subjects rate difficulty falling asleep daily on Numerical Rating Scale (0=no difficulty, 10=extremely difficult)
Phase 2a: Change from baseline in pruritis visual analog scale (VAS) over time to end of treatment, assessed up to 24 weeks At every visit, subjects rate intensity of their average pruritus over previous 3 days on 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis)
Phase 2a: Percent change from baseline in 5-D Pruritus total score over time to end of treatment, assessed up to 24 weeks 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) and 25 (most severe pruritus)
Phase 2a: Percent change from baseline in Sleep Loss VAS over time to end of treatment, assessed up to 24 weeks At every visit, subjects rate intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness)
Phase 2b: Proportion of subjects with at least 2-point improvement from baseline in PN-IGA over time to end of treatment, assessed up to 52 weeks PN-IGA, assessed at designated visits, 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)
Phase 2b: Change from baseline in weekly average of Sleep Loss VAS over time to end of treatment, assessed up to 52 weeks At every visit, subjects rate intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness)
Phase 2a: Change from baseline in weekly average of sleep quality NRS over time to end of treatment, assessed up to 24 weeks Subjects rate daily sleep quality on Numerical Rating Scale (0=best possible sleep, 10=worst possible sleep)
Phase 2a: Percent change from baseline in weekly average of sleep quality NRS over time to end of treatment, assessed up to 24 weeks Subjects rate daily sleep quality on Numerical Rating Scale (0=best possible sleep, 10=worst possible sleep)
Phase 2a: Proportion of subjects with improvement in Prurigo Nodularis Investigator Global Assessment (PN-IGA) by 2 categories over time to end of treatment, assessed up to 24 weeks PN-IGA, assessed at designated visits, 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)
Phase 2b: Proportion of subjects achieving at least a 6-point reduction from baseline in weekly average WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) to end of treatment, assessed up to 52 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
*Phase 2a: Proportion of subjects achieving at least a 4-point reduction from baseline in weekly average WI-NRS at Week 8 Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2a: Percent change from baseline in pruritus visual analog scale (VAS) at Week 8 At every visit, subjects rate intensity of their average pruritus over previous 3 days on 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis)
Phase 2a: Change from baseline in weekly average of WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) over time to end of treatment, assessed up to 24 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2a: Percent change from baseline in weekly average of WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) over time to end of treatment, assessed up to 24 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2a: Percent change from baseline in pruritis visual analog scale (VAS) over time to end of treatment, assessed up to 24 weeks At every visit, subjects rate intensity of their average pruritus over previous 3 days on 0-10 line scale (0=no pruritis, 10=worst imaginable pruritis)
Phase 2a: Change from baseline in 5-D Pruritus total score over time to end of treatment, assessed up to 24 weeks 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) and 25 (most severe pruritus)
Phase 2a: Change from baseline in weekly average of difficulty falling asleep NRS over time to end of treatment, assessed up to 24 weeks Subjects rate difficulty falling asleep daily on Numerical Rating Scale (0=no difficulty, 10=extremely difficult)
Phase 2a: Percent change from baseline in quality of life (QoL) measures (DLQI and Itchy QoL) over time to end of treatment, assessed up to 24 weeks QoL is assessed at designated visits and includes the Dermatology QoL Index (DLQI) whereby 0=no effect on quality of life; 30= extremely large effect on QoL; and Itchy QoL, administered as designated visits, which contains 22 items focused on the impact of pruritus on daily activities and on the level of psychological stress. 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)
Phase 2b: Change from baseline in weekly average of WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) over time to end of treatment, assessed up to 52 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2b: Proportion of subjects achieving at least a 6-point reduction from baseline in weekly average WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) over time to end of treatment, assessed up to 52 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2b: Proportion of subjects achieving at least a 4-point reduction from baseline in weekly average WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) over time to end of treatment, assessed up to 52 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2b: Proportion of subjects achieving 0 or 1 in Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA-CNPG-S) over time to end of treatment, assessed up to 52 weeks 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.
Phase 2a: Change from baseline in quality of life (QoL) measures (DLQI and Itchy QoL) over time to end of treatment, assessed up to 24 weeks QoL is assessed at designated visits and includes the Dermatology QoL Index (DLQI) whereby 0=no effect on quality of life; 30= extremely large effect on QoL; and Itchy QoL, administered as designated visits, which contains 22 items focused on the impact of pruritus on daily activities and on the level of psychological stress. 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)
Phase 2a: Change from baseline in Prurigo Nodularis Nodule Assessment Tool (PN-NAT) over time to end of treatment, assessed up to 24 weeks 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.
Phase 2b: Proportion of subjects achieving 0 or 1 from baseline 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 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)
Phase 2b: Proportion of subjects achieving at least a 4-point reduction from baseline in weekly average WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) at Week 16 Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2b: Percent change from baseline in weekly average of WI-NRS (Worst Itch [pruritis] - Numerical Rating Scale; 0=no pruritis, 10=worst imaginable pruritis) over time to end of treatment, assessed up to 52 weeks Subjects rate pruritus daily on Worst Itch \[pruritis\] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus)
Phase 2b: Percent change from baseline in ItchyQoL over time to end of treatment, assessed up to 52 weeks Itchy QoL, administered as designated visits, contains 22 items focused on the impact of pruritus on daily activities and on the level of psychological stress. 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)
Phase 2b: Proportion of subjects achieving 0 or 1 in PN-IGA over time to end of treatment, assessed up to 52 weeks 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)
Phase 2b: Proportion of subjects with at least 2-point improvement from baseline in IGA-CNPG-S over time to end of treatment, assessed up to 52 weeks 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.
Phase 2b: Percent change from baseline in weekly average of Sleep Loss VAS over time to end of treatment, assessed up to 52 weeks At every visit, subjects rate intensity of their average sleeplessness over previous 3 days on 0-10 line scale (0=no sleeplessness, 10=worst imaginable sleeplessness)
Phase 2b: Change from baseline in ItchyQoL over time to end of treatment, assessed up to 52 weeks Itchy QoL, administered as designated visits, contains 22 items focused on the impact of pruritus on daily activities and on the level of psychological stress. 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)
Trial Locations
- Locations (76)
Site 2701
🇧🇪Liège, Belgium
Site 2011
🇩🇪Dresden, Germany
Site 2008
🇩🇪Göttingen, Germany
Site 4303
🇰🇷Seoul, Korea, Republic of
Site 4302
🇰🇷Seoul, Korea, Republic of
Site 2201
🇵🇱Wrocław, Poland
Site 4204
🇨🇳Taoyuan City, Taiwan
Site 111
🇺🇸Pembroke Pines, Florida, United States
Site 105
🇺🇸Boise, Idaho, United States
Site 1309
🇨🇦Markham, Ontario, Canada
Site 1139
🇺🇸Centennial, Colorado, United States
Site 1165
🇺🇸North Hollywood, California, United States
Site 137
🇺🇸Colton, California, United States
Site 104
🇺🇸Anniston, Alabama, United States
Site 1107
🇺🇸Largo, Florida, United States
Site 1116
🇺🇸Fountain Valley, California, United States
Site 1167
🇺🇸Los Angeles, California, United States
Site 1127
🇺🇸Scottsdale, Arizona, United States
Site 1102
🇺🇸Los Angeles, California, United States
Site 123
🇺🇸New Albany, Indiana, United States
Site 114
🇺🇸Sandy Springs, Georgia, United States
Site 1110
🇺🇸Beverly, Massachusetts, United States
Site 1150
🇺🇸New York, New York, United States
Site 1158
🇺🇸Rochester, New York, United States
Site 1121
🇺🇸Fairborn, Ohio, United States
Site 4105
🇦🇺Woolloongabba, Queensland, Australia
Site 101
🇺🇸Houston, Texas, United States
Site 1115
🇺🇸Spokane, Washington, United States
Site 2301
🇨🇿Pardubice, Czechia
Site 4106
🇦🇺Kogarah, New South Wales, Australia
Site 2302
🇨🇿Praha 10, Czechia
Site 1307
🇨🇦Barrie, Ontario, Canada
Site 1306
🇨🇦Fredericton, New Brunswick, Canada
Site 2001
🇩🇪Bad Bentheim, Niedersachsen, Germany
Site 2504
🇫🇷Nantes, France
Site 2003
🇩🇪Bielefeld, NRW, Germany
Site 2503
🇫🇷Bordeaux, France
Site 4207
🇨🇳Taipei, Taiwan
Site 2005
🇩🇪Witten, Germany
Site 2603
🇮🇹Brescia, Italy
Site 4304
🇰🇷Incheon, Korea, Republic of
Site 2207
🇵🇱Kraków, Poland
Site 2204
🇵🇱Rzeszów, Poland
Site 2002
🇩🇪Münster, Germany
Site 4203
🇨🇳New Taipei City, Taiwan
Site 2604
🇮🇹Catania, Sicily, Italy
Site 2901
🇬🇧Leytonstone, United Kingdom
Site 4201
🇨🇳Taipei, Taiwan
Site 2903
🇬🇧Liverpool, United Kingdom
Site 117
🇺🇸Tampa, Florida, United States
Site 1133
🇺🇸Charleston, South Carolina, United States
Site 128
🇺🇸San Antonio, Texas, United States
Site 1154
🇺🇸Fremont, California, United States
Site 122
🇺🇸San Francisco, California, United States
Site 1151
🇺🇸Fort Lauderdale, Florida, United States
Site 1135
🇺🇸Miami, Florida, United States
Site 1132
🇺🇸Little Rock, Arkansas, United States
Site 1113
🇺🇸Fort Gratiot, Michigan, United States
Site 1159
🇺🇸Clinton Township, Michigan, United States
Site 130
🇺🇸Warren, Michigan, United States
Site 1118
🇺🇸Troy, Michigan, United States
Site 2102
🇦🇹Graz, Austria
Site 2101
🇦🇹Wien, Austria
Site 2702
🇧🇪Brussels, Belgium
Site 2502
🇫🇷Brest, France
Site 4104
🇦🇺Parkville, Victoria, Australia
Site 1308
🇨🇦Edmonton, Alberta, Canada
Site 1301
🇨🇦Red Deer, Alberta, Canada
Site 1305
🇨🇦London, Ontario, Canada
Site 125
🇺🇸Phoenix, Arizona, United States
Site 1155
🇺🇸Louisville, Kentucky, United States
Site 1163
🇺🇸Tampa, Florida, United States
Site 1166
🇺🇸Tampa, Florida, United States
Site 108
🇺🇸Omaha, Nebraska, United States
Site 106
🇺🇸Pflugerville, Texas, United States
Site 303
🇨🇦Saint-Jérôme, Quebec, Canada