A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of KA34 Administered Via Intra-Articular Injection in Subjects With Osteoarthritis of the Knee
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- SAD Part: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This study will evaluate the safety and tolerability of KA34 when administered via intra-articular injection to subjects with osteoarthritis of the knee.
详细描述
This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of KA34 when administered via intra-articular injection to subjects with osteoarthritis of the knee. OA patients are randomized to receive either placebo or KA34 active drug in the range of 50-400 ug by intra-articular injection. The first portion of the study is with single ascending doses, the second portion of the study is with multiple ascending doses.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of localized osteoarthritis of the knee
- •Males willing to use contraception and females who are no longer able to bear children
排除标准
- •Body Mass Index (BMI) > 40
- •Grade 0, 3 or 4 osteoarthritis on the Kellgren and Lawrence classification system
- •Injury to the knee or other joint within the last 12 months
- •Receipt of any investigational product or experimental therapeutic procedure within the last 12 weeks
研究组 & 干预措施
KA34 Active Drug
KA34 active drug in the dose range of 50 - 400 ug per knee
干预措施: KA34 (Drug)
Placebo
Placebo is the formulation for KA34.
干预措施: Placebo (Drug)
结局指标
主要结局
SAD Part: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs)
时间窗: Day 1 up to Day 29
TEAEs were collected from time of first administration of IP (Day 1) until 28 days after the last administration of IP. The severity of TEAEs was classified by the investigator as mild, moderate or severe and graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The investigator also assessed relatedness of TEAEs. The number of subjects who experienced any TEAEs, serious TEAEs (SAE), related TEAEs and TEAEs with CTCAE Grade ≥ 3 are presented.
MAD Part: Number of Subjects Who Experienced TEAEs
时间窗: Day 1 up to Day 180
TEAEs were collected from time of first administration of IP (Day 1) until 30 days after the last administration of IP. The severity of TEAEs was classified by the investigator as mild, moderate or severe and graded using the CTCAE version 5.0. The investigator also assessed relatedness of TEAEs. The number of subjects who experienced any TEAEs, SAEs, related TEAEs and TEAEs with CTCAE Grade ≥ 3 are presented.
次要结局
- MAD Part: Mean Change From Baseline in Liver Enzymes at Day 180(Baseline and Day 180)
- SAD Part: Mean Change From Baseline in the QTcF Interval at Day 8(Baseline and Day 8)
- MAD Part: Mean Change From Baseline in Hemoglobin at Day 180(Baseline and Day 180)
- MAD Part: Mean Change From Baseline in Hematocrit at Day 180(Baseline and Day 180)
- SAD Part: Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Day 8(Baseline and Day 8)
- SAD Part: Mean Maximum Plasma Concentration (Cmax)(Pre-dose up to 4 hours post-dose on Day 1)
- SAD Part: Mean Change From Baseline in Hematocrit at Day 8(Baseline and Day 8)
- SAD Part: Mean Change From Baseline in Hemoglobin at Day 8(Baseline and Day 8)
- MAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 180(Baseline and Day 180)
- MAD Part: Median Tmax(Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29)
- SAD Part: Mean Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUC[0-inf])(Pre-dose up to 4 hours post-dose on Day 1)
- MAD Part: Mean t1/2(Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29)
- SAD Part: Mean Apparent Clearance (CL/F)(Pre-dose up to 4 hours post-dose on Day 1)
- MAD Part: Mean Change From Baseline in SBP and DBP at Day 180(Baseline and Day 180)
- MAD Part: Mean Cmax(Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29)
- SAD Part: Mean Apparent Terminal Half-life (t1/2)(Pre-dose up to 4 hours post-dose on Day 1)
- SAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 8(Baseline and Day 8)
- SAD Part: Mean Change From Baseline in Liver Enzymes at Day 8(Baseline and Day 8)
- MAD Part: Mean Change From Baseline in the QTcF Interval at Day 180(Baseline and Day 180)
- MAD Part: Number of Subjects With Injection Site TEAEs(Baseline up to Day 180)
- SAD Part: Median Time to Maximum Observed Plasma Concentration (Tmax)(Pre-dose up to 4 hours post-dose on Day 1)
- MAD Part: Mean AUC(0-inf)(Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29)
- SAD Part: Number of Subjects With Injection Site TEAEs(Baseline up to Day 29)
- SAD Part: Mean Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-t])(Pre-dose up to 4 hours post-dose on Day 1)
- MAD Part: Mean AUC(0-t)(Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29)
- MAD Part: Mean CL/F(Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29)
- SAD Part: Mean Apparent Volume of Distribution (Vz/F)(Pre-dose up to 4 hours post-dose on Day 1)
- MAD Part: Mean Vz/F(Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29)