SYNERGY-1: A Phase 1 First-in-human, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Single and Multiple Doses of KP104 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of participants with Dose-limiting toxicities (DLT)
研究概览
简要总结
The purpose of this study is to evaluate safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of KP104 in healthy volunteers. The study will be conducted in 2 parts: Part 1, the single ascending dose (SAD) is the first in human (FIH) study of KP104 and Part 2, multiple ascending dose (MAD).
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Weight of > 40 kilograms (kg) and < 120 kg at Screening.
- •In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead ECG, clinical laboratory findings, and vital signs at Screening and Check-in.
- •Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, and platelet count results within the normal range at the Screening Visit; participants with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment. Tests may be repeated at the discretion of the Investigator to confirm abnormalities.
- •Creatinine clearance based on the Cockcroft-Gault equation of >= 80 milliliters per minute (ml/min).
- •Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the end of study (EOS) visit.
- •Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug; for post-menopausal subjects, a blood sample will also be tested for follicle stimulating hormone to confirm post-menopausal status.
排除标准
- •Any clinically significant underlying illness in the opinion of the Investigator.
- •Any history or sign of significant chronic active or recurrent infection, or screening laboratory evidence consistent with a significant chronic active or recurrent infection requiring treatment with antibacterials, antivirals, or antifungals.
- •Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibacterials, antivirals, or antifungals.
- •History of clinically significant hematologic or bone marrow disease or blood dyscrasias.
- •History of meningococcal infection.
- •History of tuberculosis.
- •History of asplenia (functional or anatomical).
- •Prior exposure to KP
- •Known allergy to penicillin antibiotics or history of allergy or contraindication to required prophylactic antibiotic therapy to be used during the study.
- •Known or suspected complement deficiency during screening.
- •Positive serology for Hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at Screening.
- •History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Check-in.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part 1: Single Ascending Dose Cohort 1
干预措施: KP104 (Drug)
Part 1: Single Ascending Dose Cohort 2
干预措施: KP104 (Drug)
Part 1: Single Ascending Dose Cohort 3
干预措施: KP104 (Drug)
Part 1: Single Ascending Dose Cohort 4
干预措施: KP104 (Drug)
Part 1: Single Ascending Dose Cohort 5
干预措施: KP104 (Drug)
Part 1: Single Ascending Dose Cohort 6
干预措施: KP104 (Drug)
Part 1: Single Ascending Dose Cohort 7
干预措施: KP104 (Drug)
Part 2: Multiple Ascending Dose Cohort 1
干预措施: KP104 (Drug)
Part 2: Multiple Ascending Dose Cohort 2
干预措施: KP104 (Drug)
Part 2: Multiple Ascending Dose Cohort 3
干预措施: KP104 (Drug)
Part 1: Placebo
干预措施: Placebo (Drug)
Part 2: Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with Dose-limiting toxicities (DLT)
时间窗: Up to Day 85
A DLT is defined as any adverse event considered by the investigator to be KP104-related with a severity greater than or equal to (\>=) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 which also represents a shift from baseline clinical status of \> 1 NCI CTCAE grade. A hypersensitivity/administration reaction occurring with a severity of Grade 2 despite the use of pre-medications will also be designated as a DLT.
Number of participants reporting Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to Day 85
An Adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. A TEAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Number of participants reporting Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: Up to Day 85
A TESAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Number of participants reporting AEs of Special interests (AESIs)
时间窗: Up to Day 85
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. Number of participants with AESIs including infections and local or systemic administration reactions will be assessed.
次要结局
- Maximum concentration (Cmax) of KP104(Up to Day 29)
- Change from baseline in total and free serum C5 levels(Baseline and up to Day 29)
- Area under the concentration-time profile (AUC) of KP104(Up to Day 29)
- Change from baseline in rabbit red blood cell (RBC) assay(Baseline and up to Day 29)