A Phase 1b/2a Multicenter Study to Assess the Safety and Tolerability, Pharmacokinetics, and Preliminary Efficacy of KPG-818 in Patients With Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 18
- 主要终点
- Safety assessment by out of normal range of ECG results
研究概览
简要总结
Study Title
A phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to assess the safety and tolerability, pharmacokinetics and preliminary efficacy of KPG-818 in patients with mild to moderate systemic lupus erythematosus
详细描述
This is a Phase 1b/2a multicenter study to evaluate the safety, PK, PD, and clinical efficacy of KPG-818 in patients with SLE. The trial will consist of 2 parts: Phase 1b, a multiple-ascending dose (MAD) study; and Phase 2a, a proof of concept (POC) study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
KPG-818 low dose
After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks.
干预措施: KPG-818 low dose (Drug)
KPG-818 mid dose
After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks.
干预措施: KPG-818 mid dose (Drug)
KPG-818 high dose
After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks.
干预措施: KPG-818 high dose (Drug)
Placebo arm
After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety assessment by out of normal range of ECG results
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
To calculate the occurrence rate of out of normal range of ECG results.
PK profile of time to peak (Tmax) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured on Day 1 after dose administration and after the plasma concentration reaches a steady state.
PK profile of the mean retention time (MRT) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured after the plasma concentration reaches a steady state.
PK profile of the cumulative coefficient (R) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured after the plasma concentration reaches a steady state.
Safety assessment by the changes from baseline in laboratory parameters
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
To calculate the occurrence rate of out of normal ranges of laboratory parameter changes from baseline.
PK profile of trough concentrations at steady state (Css_min) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured after the plasma concentration reaches a steady state.
PK profile of peak plasma concentration (Cmax) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured on Day 1 after dose administration.
PK profile of the clearance (CL/F) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured after the plasma concentration reaches a steady state.
Assess the proportion of patients with improvement of clinical scores of SELENA-SLEDAI (safety of estrogens in lupus national assessment-systemic lupus erythematosus disease activity index) improvement ≥ 4 points from baseline at Week 12.
时间窗: 16 weeks for phase IIa
To calculate the proportion of patients with SELENA-SLEDAI (safety of estrogens in lupus national assessment-systemic lupus erythematosus disease activity index) improvement ≥ 4 points from baseline at Week 12. Note: the SELENA-SLEDAI scale ranges from 0\~105, with 105 as the highest disease activity.
Safety assessment by the occurrence of adverse events (AEs)
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
To calculate the occurrence rate of adverse events (AEs)
Safety assessment by out of normal range of vital signs
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
To calculate the occurrence rate of out of normal range of vital signs from baseline.
PK profile of elimination half-life (t1/2) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured on Day 1 after dose administration and after the plasma concentration reaches a steady state.
PK profile of the area under the concentration-time curve (AUC0-24h) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured on Day 1 after dose administration.
PK profile of peak concentrations at steady state (Css_max) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured after the plasma concentration reaches a steady state.
PK profile of the area under the concentration-time curve at steady state (AUCτ, AUC0-∞) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured after the plasma concentration reaches a steady state.
PK profile of the apparent volume of distribution ((Vz/F) for KPG-818 and KPG-818H (if applicable).
时间窗: 4 weeks for phase Ib and 16 weeks for phase IIa
This will be measured after the plasma concentration reaches a steady state.
次要结局
- The PK endpoint of Ctrough throughout the dosing period for assessment of KPG-818 and KPG-818H (if applicable)(12 weeks for phase IIa)
- Number of patients with adverse event at Week 12(12 weeks for phase IIa)
- Number of patients with adverse event at Week 16.(16 weeks for phase IIa)
- The PK endpoint of the measurement of area under the curve (AUC) at Week 12 (AUC0-last) for assessment of KPG-818 and KPG-818H (if applicable).(12 weeks for phase IIa)
- The PK endpoint of time to Cmax (tmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable)(12 weeks for phase IIa)
- The PK endpoint of serum concentrations by scheduled timepoints for assessment of KPG-818 and KPG-818H (if applicable)(12 weeks for phase IIa)
- Mean change from baseline in PGA (Physician Global Assessment) score at Week 12.(16 weeks for phase IIa)
- The proportion of patients with a ≥ 50% reduction from baseline in CLASI (Cutaneous Lupus erythematosus disease Area and Severity Index) activity score at Week 12, in patients with baseline CLASI activity score ≥ 10.(16 weeks for phase IIa)
- The PK endpoint of the maximum observed concentration (Cmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable)(12 weeks for phase IIa)