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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 160
- 主要终点
- Phase 2a & 2b: Percent Change From Baseline in Weekly Average Worst Itch-Numeric Rating Scale (WI-NRS) Score
研究概览
简要总结
Study of the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of Vixarelimab (KPL-716) in subjects with prurigo nodularis (PN).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(apply to both Phase 2a and Phase 2b unless otherwise specified):
- •Male or female aged 18 to 75 years (Phase 2a), 18 to 80 years (Phase 2b)
- •Have clinical diagnosis of prurigo nodularis for at least 6 months
- •Have at least 10 nodules (Phase 2a), 20 nodules (Phase 2b) at the Screening Visit and Day 1
- •Moderate to severe pruritus (Phase 2a); severe pruritus (Phase 2b)
- •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
- •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
排除标准
- •(apply to both Phase 2a and Phase 2b unless otherwise specified):
- •Use of prohibited medications within the indicated timeframe from Day 1
- •Is currently using medication known to cause pruritus
- •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
- •Laboratory abnormalities that fall outside the windows specified in the protocol at the Screening Visit
- •Has an active infection, including skin infection
- •Any medical or psychiatric condition which, in the opinion of the Investigator or the Sponsor, may place the 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
研究组 & 干预措施
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)
干预措施: Vixarelimab (Drug)
Phase 2a - Placebo SC QW
Placebo loading dose followed by placebo weekly for 8 weeks (Protocol Version 3) or 16 weeks (Protocol Version 2)
干预措施: Placebo (Drug)
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
干预措施: Vixarelimab (Drug)
Phase 2b - Vixarelimab 360 mg SC, Q4W (DBL)
Vixarelimab 360 mg SC, every 4 weeks (Q4W) for 16 weeks during Double Blind Period
干预措施: Vixarelimab (Drug)
Phase 2b - Vixarelimab 120 mg SC, Q4W (DBL)
Vixarelimab 120 mg SC, every 4 weeks (Q4W) for 16 weeks during Double Blind Period
干预措施: Vixarelimab (Drug)
Phase 2b - Placebo SC, Q4W (DBL)
Placebo SC, every 4 weeks (Q4W) for 16 weeks during Double Blind Period
干预措施: Placebo (Drug)
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
干预措施: Vixarelimab (Drug)
结局指标
主要结局
Phase 2a & 2b: Percent Change From Baseline in Weekly Average Worst Itch-Numeric Rating Scale (WI-NRS) Score
时间窗: at Week 8 (Phase 2a); at Week 16 (Phase 2b)
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.
次要结局
- Phase 2a: Percentage of Participants Achieving at Least a 4-point Reduction From Baseline in Weekly Average WI-NRS at Week 8(Baseline, Week 8)
- Phase 2a: Percent Change From Baseline in Pruritus Visual Analog Scale (VAS) at Week 8(Baseline, Week 8)
- Phase 2a: Change From Baseline in Weekly Average of WI-NRS Over Time(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(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(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(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(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(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(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(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(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(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(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(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(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(Baseline, Weeks 2, 4, 6, 8, 12, 16, 24)
- Phase 2a: Percent Change From Baseline in QoL Measure DLQI Over Time(Baseline, Weeks 2, 4, 6, 8, 12, 16, 24)
- Phase 2a: Change From Baseline in QoL Measure Itchy Quality of Life (ItchyQoL) Over Time(Baseline, Weeks 2, 4, 6, 8, 12, 16, 24)
- Phase 2a: Percent Change From Baseline in QoL Measure Itchy QoL Over Time(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(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(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(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(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(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(Baseline, Week 16)
- Phase 2b: Percentage of Participants Achieving a Score of 0 or 1 in PN-IGA at Week 16(Week 16)
- Phase 2b: Change From Baseline in Weekly Average of WI-NRS Over Time(Baseline, Weeks 1 through 52)
- Phase 2b: Percent Change From Baseline in Weekly Average of WI-NRS Over Time(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(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(Baseline, Weeks 1 through 52)
- Phase 2b: Percentage of Participants Achieving 0 or 1 in PN-IGA Over Time(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(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(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(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(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(Baseline, Weeks 2, 4, 8, 12, 16, 18, 20, 32, 48, 52)
- Phase 2b: Change From Baseline in ItchyQoL Over Time(Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52)
- Phase 2b: Percent Change From Baseline in ItchyQoL Over Time(Baseline, Weeks 4, 8, 12, 16, 18, 20, 32, 48, 52)