A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Single Ascending and Multiple Ascending Dose Study Investigating PRA-216 in Healthy Volunteers Followed by a Phase 2a Randomized, Double-Blind, Placebo-Controlled Study in Participants With Mild-to-Moderate Asthma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 96
- 试验地点
- 8
- 主要终点
- Phase 1: Incidence, nature, and severity of serious adverse events (SAEs) with a single dose of PRA-216 in healthy volunteers (SAD arm)
研究概览
简要总结
Phase 1 of this study will consist of 2 parts
- Part 1 will evaluate the safety, tolerability, pharmacokinetics and immunogenicity of PRA-216 in healthy volunteers through single ascending dose administered by either intravenous (IV) or subcutaneous (SC).
- Part 2 will evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of PRA-216 in healthy volunteers with repeat doses of multiple ascending dose administered subcutaneously.
Phase 2a of this study is a randomized, double-blind, placebo-controlled study to investigate the efficacy, safety and immunogenicity of PRA-216 in participants with mild to moderate asthma. The dose of PRA-216 for this phase was determined from Phase 1.
详细描述
This study is a Phase 1/2a randomized, double-blind, placebo-controlled, single- and multiple-dose study with staggered dose escalations in healthy participants and participants with mild to moderate asthma. Single-ascending dose (SAD) cohorts will be evaluated for one single dose administered. Multiple ascending dose (MAD) cohorts will be evaluated for repeat doses .
Participants with mild to moderate asthma will be recruited for Phase 2a of this study, to evaluate safety of randomized, double blind, placebo controlled PRA-216. The dose of PRA-216 for this phase was determined from Phase 1 safety, tolerability, and PK data. Additional dose levels or schedules may be used for Phase 2a, depending on data from Phase 1.
This study consists of 2 phases, as follows:
Phase 1, Part 1:
SAD in healthy volunteers. Study visits in this section will entail a single dose administration of PRA-216 or placebo and collection of study data.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion Criteria:
- •Age 18-65
- •Must be in good health with no significant medical history
- •Willing and able to attend all study visits, comply with study requirements
- •Able and willing to provide written informed consent
排除标准
- •Evidence of clinically significant condition or disease
- •Any physical or psychological condition that prohibits study completion
- •Known history of illicit drug use or drug abuse, harmful alcohol use (at the Investigator's discretion), alcoholism, and/or smoking or nicotine-containing product use within 3 months prior to the first dose of study agent
- •History of severe allergic reactions or hypersensitivity
- •Donation or loss of ≥ 1 unit of whole blood or plasma within 2 months prior to dosing
- •Inclusion criteria:
- •Age 18-65
- •Must be in good health with no significant medical history
- •Willing and able to attend all study visits, comply with study requirements.
- •Able and willing to provide written informed consent
- •Documented asthma diagnosis prior for at least 12 months prior to screening.
- •Symptomatic asthma
- •Currently receiving maintenance asthma medications
- •Exclusion Criteria:
- •Evidence of clinically significant condition or disease
- •Known history of illicit drug use or drug abuse, harmful alcohol use (at the Investigator's discretion), alcoholism, and/or smoking or nicotine-containing product use within 3 months prior to the first dose of study agent
- •Donation or loss of ≥ 1 unit of whole blood or plasma within 2 months prior to dosing
- •History of severe allergic reactions or hypersensitivity
- •Current or former smoker with a smoking history of ≥10 pack-years
- •Receipt of immunosuppressant therapies or biologic therapy for asthma within 6 months of screening
- •Other investigational agent(s) within 30 days of dosing
研究组 & 干预措施
Phase 1, Part 1: SAD Cohorts: Active Drug
Healthy volunteers will receive a single dose of PRA-216 in a dose escalation format.
干预措施: PRA-216 (Drug)
Phase 1, Part 1: SAD Cohorts: Placebo
Healthy volunteers will receive a single dose of placebo
干预措施: Placebo (Drug)
Phase 1, Part 2: MAD Cohort: Active Drug
Healthy volunteers will receive repeated doses of PRA-216 in a dose escalation format.
干预措施: PRA-216 (Drug)
Phase 1, Part 2 MAD Cohort: Placebo Comparator
Healthy volunteers will receive repeated doses of placebo comparator.
干预措施: Placebo (Drug)
Phase 2a: Participants with mild to moderate asthma-active drug
Participants with mild to moderate asthma will be randomized to receive repeat doses of PRA-216.
干预措施: PRA-216 (Drug)
Phase 2a: Participants with mild to moderate asthma-placebo
Participants with mild to moderate asthma will be randomized to receive repeat doses of placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Phase 1: Incidence, nature, and severity of serious adverse events (SAEs) with a single dose of PRA-216 in healthy volunteers (SAD arm)
时间窗: Up to Study Day 169
Incidence, nature, and severity of serious adverse events (SAEs)
Phase 1: Incidence, nature, and severity of serious adverse events (SAEs) of multiple doses of PRA-216 in healthy volunteers (MAD arm)
时间窗: up to Study Day 169
Incidence, nature, and severity of and serious adverse events (SAEs)
Phase 2a: To evaluate the effect of multiple doses of PRA-216 compared to placebo on exhaled nitric oxide (FeNO) in asthma participants
时间窗: Up to Study Day 57
Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of airway inflammation in asthma.
次要结局
- Phase 1: Immunogenicity of PRA-216: ADA in healthy volunteers(Up to Study Day 169)
- Phase 1: Pharmacokinetics of PRA-216: Tmax in healthy volunteers(Up to Study Day 169)
- Phase 1: Pharmacokinetics of PRA-216: AUC in healthy volunteers(Up to Study Day 169)
- Phase 1: Pharmacokinetics of PRA-216: Cmax in healthy volunteers(Up to Study Day 169)
- Phase 2a: Incidence, nature, and severity of serious adverse events (SAEs) of PRA-216 in patients with asthma(Up to Study Day 197)
- Phase 2a: Immunogenicity of PRA-216: ADA in patients with asthma(Up to Study Day 197)
- Phase 2a: Pharmacokinetics of PRA-216: Tmax in patients with asthma(Up to Study Day 197)
- Phase 2a: Pharmacokinetics of PRA-216: AUC in patients with asthma(Up to Study Day 197)
- Phase 2a: Pharmacokinetics of PRA-216: Cmax in patients with asthma(Up to Study Day 197)