Community Participants With COPD or Bronchiectasis and at Risk of Respiratory Viral Infections Including SARS-CoV-2: An Open-label, Multicentre Feasibility Study of an Inhaled Nitric Oxide Generating Solution (RESP301)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 88
- 试验地点
- 2
- 主要终点
- Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1
研究概览
简要总结
Patients with a respiratory disease are at higher risk of poor outcomes due to worsening of symptoms caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and other respiratory infections. New therapies are needed for treating high risk patients at early stages of an infection. This study will assess the safety, tolerability and feasibility of using an inhaled nitric oxide generating solution, RESP301, as a self-administered treatment following flare-up of symptoms.
RESP301 is a liquid solution which produces nitric oxide in the lungs when inhaled using a nebuliser. The components of RESP301 are already used in clinical practice and inhaled nitric oxide is used as a treatment for newborns and patients with Chronic Obstructive Pulmonary Disease (COPD). In a laboratory setting, RESP301 has been shown to be effective against respiratory viruses, including SARS-CoV-2.
This study will first determine the maximum tolerated dose of RESP301 in up to 48 adult patients with COPD or bronchiectasis in the United Kingdom (UK) (Part 1a; Dose Finding Phase). Once the Maximum Tolerated Dose (MTD) has been determined in Part 1a, a cohort of 8 patients will be recruited and RESP301 administered at the MTD but these patients will in addition receive a single dose of a short acting bronchodilator 10 minutes preceding administration of RESP301.
After completion of Part 1, approximately 150 patients will be recruited into Part 2 of the trial (Expansion Phase). A minimum of 50 participants will receive a test dose of RESP301 during a screening visit. Response to the test dose will be monitored. Participants who tolerate the test dose will continue in the study and should contact the study team if they experience exacerbation symptoms in the next 52 weeks. Following a call with the site team to discuss symptoms, participants will receive RESP301 delivered to their home to self-administer for 7 days. The study duration for each participant will be at most 57 weeks, including the study visit and monthly calls. Participants who start the course of study treatment, will receive daily calls during the treatment period and will also be followed up after they complete the treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female of non-childbearing potential or male ≥35 years of age, at the time of signing the informed consent
- •Able and willing to provide informed consent
- •Spirometry-confirmed diagnosis of COPD (FEV1/FVC<0.7 post-bronchodilator) or computerised tomography (CT) proven bronchiectasis
- •Part 1 only: FEV1 ≥50% predicted at screen 1 (i.e. FEV1 prior to any in-clinic administered short acting bronchodilator)
排除标准
- •Unable to safely use a nebuliser as required by the study according to Investigator's opinion
- •Severe COPD or bronchiectasis defined as FEV1 <20% or requiring non-invasive ventilation
- •History of methaemoglobinaemia
- •Baseline methaemoglobin concentration (using fingertip sensor) > 2%
- •Uncontrolled or severe asthma or history of severe bronchospasm
- •Presence of tracheostomy/inability to provide spirometry or contraindication for performing spirometry
- •Allergy to any of the components of the study intervention
- •Participation in other clinical investigations utilising investigational treatment within the last 30 days / 5 half lives whichever is longer
- •Deemed unlikely to be able to adhere to protocol in view of investigator
- •Any subject who in the opinion of the investigator would not be best served by participating in this clinical trial
- •Any unstable, uncontrolled or severe medical condition which in the opinion of the investigator would make the patient unsuitable for the trial
- •Participant lives at home with no other adults in the household (Part 2 only)
- •On long-term non-invasive ventilation and/or at higher risk of bronchospasm
- •Prescribed Nitric Oxide donating agent (Nitroprusside, Isosorbide dinitrate, Isosorbide mononitrate, Naproxcinod, Molsidomine and Linsidomine)
- •Female of childbearing potential
- •Clinical diagnosis of COPD but Screening Visit spirometry at study centre excludes COPD (i.e. FEV1/FVC post bronchodilator ratio is not <0.7)
研究组 & 干预措施
All participants
In Part 1a, up to 48 patients will be administered single ascending doses of RESP301 (1-6ml; 8 patients per dose cohort). Provided that individual stopping criteria are not met in ≥3 participants, and there are no serious adverse events that are at least possibly related to RESP301, the next dose cohort can be enrolled. Patients can be enrolled into more than one dose cohort provided they did not meet individual stopping criteria.
In Part 1b, 8 participants will receive RESP301 at MTD determined in Part 1a, with short-acting bronchodilator administered 10min prior to RESP301.
In Part 2, a minimum of 150 patients will be enrolled. This may include patients who took part in Part 1. At least the first 50 patients will receive a test dose of RESP301 before enrolment into the "dormant phase". Patients who experience flare-up symptoms while in the dormant phase, may proceed to the treatment phase where they will self-administer RESP301 at home for 7 days.
干预措施: RESP301 (Drug)
结局指标
主要结局
Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1
时间窗: Screening Visit
Defined as percentage of participants able to tolerate the test dose, i.e. able to complete the test dose without any of the following: * Troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient * methaemoglobin \>5% during or \>3% post dose (60 mins) * any treatment-related AE that led to participant not being able to complete the test dose * \>20% reduction in FEV1 pre dose to post dose at 60min if additionally reporting troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient
Feasibility of Self-administering RESP301 Treatment in Terms of Commencing Treatment
时间窗: 1 day
Defined as percentage of patients who, having experienced and correctly reported an exacerbation, commence self-administration of the treatment on the day the treatment is delivered
Feasibility of Self-administering RESP301 Treatment in Terms of Treatment Compliance
时间窗: 7 days
For those participants commencing self-administration of RESP301, the percentage of total doses taken
次要结局
- Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2)(Screening Visit)
- Safety of RESP301 in Terms of Treatment Emergent Adverse Events(Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination))
- Safety of RESP301 in Terms of Serious Adverse Events(Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination))
- Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions(Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination))
- Safety of RESP301 in Terms of Treatment-related AEs(Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination))
- Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 7(7 days)
- Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 14(7 days)
- Efficacy of RESP301 in Terms of Time to Recovery(21 days)
- Efficacy of RESP301 in Terms of Preventing Exacerbation-related Hospitalisation and/or Death(7 days)
- Efficacy of RESP301 in Terms of Patient-reported Symptoms(7 days)
- Feasibility of Self-administering RESP301 Treatment in Terms of Receiving Treatment(2 days)