Study of the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of Vixarelimab (KPL-716) in subjects with prurigo nodularis (PN).
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
240
solution for injection
solution for injection
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.
Time frame: at Week 8 (Phase 2a); at Week 16 (Phase 2b)
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).
Time frame: 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)
Time frame: 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).
Time frame: 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.
Time frame: 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
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Arizona Research Center
Phoenix, Arizona, United States
Investigate MD, LLC
Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
First OC Dermatology
Fountain Valley, California, United States
Center for Dermatology Clinical Research, Inc.
Fremont, California, United States
Dermatology Research Associates
Los Angeles, California, United States
Wallace Medical Group, Inc.
Los Angeles, California, United States
Velocity Clinical Research - North Hollywood
North Hollywood, California, United States
Colorado Center for Dermatology, PLLC
Centennial, Colorado, United States
George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
...and 76 more locations
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)
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 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 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).
Time frame: 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 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.
Time frame: 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).
Time frame: 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 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 16, 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.
Time frame: 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.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: Baseline, 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 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52