A Phase 1b, Randomized, Subject- and Investigator-Blinded, Placebo-Controlled, Multi-Center Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Biomarkers of Inhaled GB002 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension (PAH)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 14
- 主要终点
- Number of participants with Treatment-Related Adverse Events GB002 (OLE study)
研究概览
简要总结
This is a Phase 1B, randomized, participant- and investigator-blinded, placebo-controlled, multi-center clinical trial to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and biomarkers of inhaled GB002 in adults with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH).
详细描述
The primary objective for this trial is to evaluate the safety and tolerability of GB002. The secondary objective for this trial is to evaluate the PK parameters of GB002. Exploratory objectives are to evaluate the PD readouts, change in WHO Group I functional class, and change in quality of life associated with GB002 treatment.
In this Phase 1B study, two dose levels of GB002 will be tested in adult participants with PAH. Four participants in cohort 1 will be randomized to receive up to two daily doses of either active drug or placebo, with 3 subjects receiving GB002 and 1 subject receiving placebo. An additional 4 participants (3 active and 1 placebo) may be added to cohort 1 at the discretion of the Data Review Committee (DRC). The dose and dosing interval (i.e., once daily or twice daily) for the second cohort will be determined by review of the safety, tolerability, and drug levels in the blood from cohort 1. Cohort 2 participants will also be randomized such that 6 subjects receive GB002 and 2 subjects receive placebo.
Eligible subjects who have completed the 2 week treatment period have the option to participate in a 24 week open label extension.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Clinical site investigators, study personnel, and study subjects will be blinded to treatment assignment; however, the Sponsor will be unblinded.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult (males and females) aged 18 to 75 years (inclusive) with pulmonary arterial hypertension (PAH) (Main study)
- •A current diagnosis of symptomatic PAH classified by one of the following (Main and OLE study):
- •Idiopathic (IPAH) or heritable pulmonary arterial hypertension (HPAH)
- •PAH associated with one of the following connective tissue diseases (CTDs):
- •systemic sclerosis, rheumatoid arthritis, mixed CTD or overlap syndrome, or systemic lupus erythematosus
- •PAH associated with anorexigen or methamphetamine use
- •World Health Organization (WHO)/New York Heart Association (NYHA) functional class II-IV symptomatology (Main study)
排除标准
- •Clinically significant systemic hypertension or hypotension (Main and OLE study)
- •History of left-sided heart disease and/or clinically significant cardiac disease (Main and OLE study)
- •History of decompensated right heart failure within 30 days of screening (e.g., hospitalization for PAH or the need to add an additional PAH medication) (Main study)
- •NOTE: Additional inclusion/exclusion criteria may apply, per protocol.
研究组 & 干预措施
Cohort 1
Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days
干预措施: GB002 (Drug)
Cohort 1
Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days
干预措施: Placebo (Drug)
Cohort 1
Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days
干预措施: Generic Dry Powder Inhaler (Device)
Cohort 2
Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days
干预措施: GB002 (Drug)
Cohort 2
Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days
干预措施: Placebo (Drug)
Cohort 2
Patients will be randomized to receive inhaled GB002 or Placebo daily for 14 days
干预措施: Generic Dry Powder Inhaler (Device)
Open Label Extension
Eligible subjects may participate in the Open Label Extension (OLE) study for a period of 24 weeks.
干预措施: GB002 (Drug)
Open Label Extension
Eligible subjects may participate in the Open Label Extension (OLE) study for a period of 24 weeks.
干预措施: Generic Dry Powder Inhaler (Device)
结局指标
主要结局
Number of participants with Treatment-Related Adverse Events GB002 (OLE study)
时间窗: Up to 200 days
To evaluate the long-term safety and tolerability and efficacy of GB002
Number of participants with Treatment-Related Adverse Events GB002 (Main study)
时间窗: Up to 45 days
To evaluate the safety and tolerability of GB002
次要结局
- Changes from baseline in 6-Minute Walk Test (6MWT) (OLE study)(169 days)
- Pharmacokinetics: Maximum Concentration (Cmax) of GB002 (Main study)(14 days)
- Changes from baseline in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) Quality of Life questionnaire (OLE study)(197 days)
- Pharmacokinetics: Area Under the Concentration Curve (AUC) of GB002 (Main study)(14 days)
- Changes from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) (OLE study)(169 days)
- Changes from baseline in WHO Functional Class (OLE study)(197 days)
- Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of GB002 (Main study)(14 days)
- Changes from baseline in Right Ventricular function by imaging (OLE study)(169 days)