A Phase 2b Open-Label, Single Arm Study to Evaluate the Efficacy of Voxelotor for Improving Oxygen Saturation and Reducing Ventilatory Support Requirements in Adult Patients With New or Increased Oxygen Requirement
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Change in SpO2/FiO2 (S/F) Ratio From Baseline to 2 Days After Initiation of Voxelotor Treatment
研究概览
简要总结
The purpose of the study is to evaluate the efficacy of voxelotor for increasing oxygen saturation in 20 patients with hypoxemia. Specifically, the SpO2/FiO2 ratio will be compared before and after voxelotor use at rest and during exercise (ambulatory patients only).
The primary study objective is to evaluate the efficacy of voxelotor for increasing oxygen saturation in patients with hypoxic hypoxemia as a result of end-stage lung disease or acute lung injury.
The secondary objective is to evaluate the efficacy of voxelotor on allowing de-escalation of supplemental oxygen support.
详细描述
Purpose of the study: Primary study objective is to evaluate the efficacy of voxelotor for increasing oxygen saturation in patients with hypoxic hypoxemia as a result of end-stage lung disease or acute lung injury.
Design and Procedures: The day after obtaining written informed consent, 20 patients will receive 500 mg of voxelotor two times a day (for a total daily dose of 1000 mg per day) for 5 days This dose may increase to a total maximum daily dose of 1500 mg (500 mg three times a day) if subject tolerates initial dose as determined by Principal Investigator (PI).
Physiological data at screening, baseline, study day 1 - 5, and up to two days post voxelotor administration will be recorded from standard of care with the only exception being SpO2/FiO2 (S/F) ratio measurements, which will be obtained at the same intervals but by the qualified and delegated study staff or medical team through the use of an FiO2 weaning maneuver.
Study subjects will be asked to rate their dyspnea symptoms daily to record their perceived shortness of breath.
Blood samples will be collected the day prior to voxelotor administration, on study days 1 - 5, and on the 2 wash-out days following voxelotor administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Oxygen dependency due to an end-staged lung disease (pre-lung transplant population) or ALI/acute lung injury (for example but not limited to primary allograft dysfunction, infectious pneumonia, aspiration, non-cardiogenic pulmonary edema). ALI will be defined as per Berlin criteria with a P/F ratio <100 denoting severe ARDS, <200 denoting moderate and <300 mild ARDS. ALI and mild ARDS are considered synonymous. In the event of inability to obtain arterial blood gas analysis to calculate a P/F ratio, we will consider a range of patients requiring standard nasal cannulae flowing at 6l/min to maintain SaO2 >90% as ALI, and Salter High -Flow nasal cannulae at 12-15l/min in order to maintain SaO2>85% as severe ARDS.
- •At least 48 hours of stable, increased oxygen requirement or ventilatory support prior to the start of drug administration if consented.
排除标准
- •Minors (<18 years)
- •Pre-existing congestive cardiac failure (NYHA III or IV)
- •Medically significant, non-revascularized coronary artery disease
- •Inability to obtain informed consent from LAR
- •Pregnancy
- •Incarcerated individual.
- •Failure of another vital organ.
- •Severe hepatic impairment (Childs-Pugh C) or liver enzymes > 4x upper limit of normal (ULN) at screening.
- •Unstable acute kidney injury/rising creatinine.
- •Chronic neuromuscular disease requiring mechanical ventilation
- •Not anticipated to survive >48 hours
- •Limited therapeutic goals (do not resuscitate, etc.)
- •History of Pulmonary Embolism (PE)
- •Requires treatment with Fluconazole or other moderate and strong CYP3A4 inhibitors listed in section 5.6
- •A patient with active bleeding complications requiring more than 1 unit of blood transfusion per day, as the PK and PD of Voxelotor in the setting of blood loss and blood transfusion is unknown.
- •Participated in another clinical trial of an investigational drug (or medical device) within 30 days or 5-half-lives, whichever is longer, prior to consent, or is currently participating in another trial of an investigational or marketed drug (or medical device)
- •Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- •Any condition or concomitant medication that confounds the ability to interpret data from the study or safely use Voxelotor.
研究组 & 干预措施
Voxelotor Arm
500 mg of Voxelotor two times a day (for a total daily dose of 1000 mg per day) for 5 days. This dose may increase to a total maximum daily dose of 1500 mg (500 mg three times a day), if subject tolerates the initial dose as determined by study doctor.
干预措施: Voxelotor (Drug)
结局指标
主要结局
Change in SpO2/FiO2 (S/F) Ratio From Baseline to 2 Days After Initiation of Voxelotor Treatment
时间窗: baseline to 2 days after initiation of voxelotor treatment
SpO2 (oxygen saturation) is the percentage of oxygen in the blood. The fraction of inspired oxygen (FiO2) is the concentration of oxygen a person inhales.
次要结局
- Change in SpO2/FiO2 (S/F) Ratio From Baseline to 5 Days After Initiation of Voxelotor Treatment(baseline to 5 days after initiation of voxelotor treatment)
研究者
Ian Welsby, MD
Principal Investigator
Duke University