NCT06677307终止1 期
A Phase 1/2a, Single- and Multiple-dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of KRRO 110 in Healthy Adult Volunteers and in Adult Participants With Alpha-1 Antitrypsin Deficiency (AATD) (REWRITE)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 42
- 试验地点
- 7
- 主要终点
- Safety and Tolerability
研究概览
简要总结
The purpose of this first-in human (FIH) study is to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of KRRO-110 in both healthy adult participants and in clinically stable patients with Alpha-1 antitrypsin deficiency (AATD).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part A SAD cohort Inclusion Criteria (Healthy Volunteers)
- •Adult male or female participants, 18 to 65 years of age
- •Documented PiMM genotype
- •Participants who are willing to and able to provide signed written informed consent
- •PiZZ Genotype (Part A SAD and Part B MAD cohorts) Inclusion Criteria (PiZZ Genotype)
- •Adult male or female participants 18 to 70 years of age (inclusive)
- •Documented PiZZ genotype
- •Baseline blood total AAT level < 11 µM/L
排除标准
- •Exclusion Criteria (Healthy Volunteers)
- •Female participant of childbearing potential or male participant that is unable or unwilling to use an approved, reliable means of contraception
- •Body mass index (BMI) > 32 or < 18.5 kg/m2
- •History or current clinical evidence of hepatic disease
- •Evidence of active infection
- •History of medical condition(s), eg, advance cardiac disease, current or recent malignancy, organ transplantation, or other illness
- •Serology result indicative of any exposure (past or active) to hepatitis C, hepatitis B, or human immunodeficiency virus (HIV)
- •Respiratory or other acute illness within 8 weeks
- •Tobacco use of any kind within 6 months
- •Exclusion Criteria (PiZZ Genotype)
- •Female participant of childbearing potential or male participant that is unable or unwilling to use an approved, reliable means of contraception
- •BMI > 32 or < 18.5 kg/m2 or weight > 90 kg
- •History of FEV1 < 35%
- •History or current clinical evidence of advanced hepatic disease and/or pulmonary disease
- •Use of an experimental therapy except KRRO-110 within 6 months or 5 half-lives for the experimental therapy, whichever is greater
- •Tobacco use of any kind within 6 months
- •Use of conventionally dosed AAT augmentation therapy within 5 half-lives
- •Serology result consistent with exposure to HIV, or serology consistent with active hepatitis B or hepatitis C infection
研究组 & 干预措施
Arm 2: Placebo (Part A only)
Placebo Comparator
Placebo, IV administration
干预措施: KRRO-110 (Drug)
Arm 1: KRRO-110 (Part A and Part B)
Experimental
KRRO-110 is an RNA editing oligonucleotide encapsulated in a lipid nanoparticle (LNP) administered by intravenous (IV) infusion as a single dose in Part A (SAD), multi-dose in Part B (MAD).
干预措施: KRRO-110 (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: From Day 1 to Day 43 in the SAD and from Day 1 to Day 85 in the MAD
Type, frequency, and severity of treatment-emergent adverse events (TEAEs)
次要结局
- Pharmacodynamics (PD) of KRRO-110(Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD))
- Pharmacokinetics (PK) of KRRO-110(Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD))
研究者
研究点 (7)
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