A First in Human, Double-blind, Placebo-controlled, Multicentre Phase I/II Study to Evaluate the Safety, Tolerability and Immune Modulatory Effects of MRx-4DP0004 in Participants Taking Long-term Control Medication for Their Asthma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 34
- 试验地点
- 4
- 主要终点
- Number of participants in each treatment arm experiencing adverse events
研究概览
简要总结
This is a multicentre, phase I/II, double-blind, placebo-controlled study of MRx-4DP0004 in participants taking long-term medication for asthma. Participants will take two capsules of MRx-4DP0004 twice daily in addition to their existing asthma medication for 12 weeks. Safety and tolerability and immune modulatory effects of MRx-4DP0004 will be assessed throughout the study.
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
- Double (Participant, Investigator)
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
- 否
入选标准
- •Documented history and diagnosis of asthma at least 6 months prior to Visit
- •Stable current asthma treatment as per GINA steps 2-4 (ICS with or without LABA) for at least 2 months prior to Visit
- •ACQ-6 score >1.5 and <=4
- •FEV1 >50% of predicted normal
- •Following protocol specified contraception requirements.
排除标准
- •Non-compliant with prescribed asthma maintenance treatment.
- •At significant risk of exposure to a change in environmental sensitising substances during the study.
- •Co-morbidities not optimally controlled for the last 3 months or any co-morbidity that may put the subject at risk or influence the outcome of the study.
- •Hepatitis B or C or HIV.
- •GI fistula, feeding tubes or inflammatory bowel disease.
- •GI disease resulting in inability for oral intake, malabsorption syndrome, surgical procedures affecting absorption, uncontrolled inflammatory bowel disease.
- •History of life-threatening asthma.
- •Systemic corticosteroids within 6 weeks of first dose.
- •Allergy to all of ampicillin, clindamycin and imipenem.
- •Probiotic supplements.
- •Immunosuppression or immunosuppressant medication.
- •Use of ICS and LABA as Maintenance and Reliever Therapy.
- •Smokers or nicotine users within 3 months of screening.
- •Former smokers >15 pack years.
- •Systemic antibiotics within 6 weeks of first dose.
- •Clinically significant haematology and serum biochemistry.
- •Sensitivity to any constituent of IMP.
- •Diastolic blood pressure <45 or >90, systolic blood pressure <95 or >155mmHg, Pulse rate <40 or >100 bpm.
- •Clinically significant ECGs or structural cardiac abnormalities.
- •Any other condition that may interfere with primary objective.
- •Receipt of a positive COVID-19 test result within 4 weeks of first dose of IMP
研究组 & 干预措施
MRx-4DP0004
MRx-4DP0004 is a Live Biotherapeutic Product containing 10^9 to 10^10 Colony Forming Units.
Participants randomised to this arm will take 2 capsules twice daily at approximately 12 hour intervals for 12 weeks.
干预措施: MRx-4DP0004 (Drug)
Placebo
Participants randomised to this arm will take 2 capsules of placebo twice daily at approximately 12 hour intervals for 12 weeks.
All participants will receive placebo in a single blind manner for two weeks in addition to the 12 weeks of double blind treatment.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants in each treatment arm experiencing adverse events
时间窗: Baseline to Day 127
Adverse events will be considered alongside other primary outcome measures for assessment of safety and tolerability.
Number of clinically relevant adverse changes in clinical laboratory tests in each treatment arm
时间窗: Baseline to Day 127
Clinically relevant adverse changes clinical laboratory tests will be considered alongside other primary outcome measures for assessment of safety and tolerability. Clinical laboratory tests will include clinical chemistry, haematology and urinalysis.
Number of clinically relevant adverse changes in vital signs in each treatment arm
时间窗: Baseline to Day 127
Clinically relevant adverse changes in vital signs will be considered alongside other primary outcome measures for assessment of safety and tolerability. Vital signs assessments will include measurement of systolic blood pressure, diastolic blood pressure, oral body temperature and pulse rate.
Number of clinically relevant adverse changes in 12-lead ECGs in each treatment arm
时间窗: Baseline to Day 127
The number of participants experiencing clinically relevant adverse changes in Clinically relevant adverse changes in vital signs will be considered alongside other primary outcome measures for assessment of safety and tolerability. ECG assessments will include measurement of PR, QRS, QT and QTcF.
次要结局
- Difference in the change from baseline in Forced Expiratory Volume in 1 second (FEV1) between treatment arms(Baseline to Day 99)
- Difference in the change from baseline in Peak Expiratory Flow (PEF) between treatment arms(Baseline to Day 99)
- Difference in the change from baseline in Forced Vital Capacity (FVC) between treatment arms(Baseline to Day 99)
- Difference in the change from baseline in blood eosinophils between treatment arms(Baseline to Day 99)
- Difference in the change from baseline in blood neutrophils between treatment arms(Baseline to Day 99)
- Difference in the change from baseline in use of short-acting beta agonists (SABAs) between treatment arms(7 period prior to baseline to 7 day period prior to Day 99)
- Difference in the mean change from baseline in the Asthma Quality of Life Questionnaire (standardised version) (AQLQ(S)) between treatment arms(Baseline to Day 99)
- Difference in the mean change in the Asthma Control Questionnaire (ACQ-6) between treatment arms(Baseline to Day 99)
- Difference in the number of subjects achieving good asthma control (as defined by an ACQ-6 score <1.0) between treatment arms.(Baseline to Day 99)
- Difference in the number of asthma exacerbations between treatment arms(Baseline to Day 99)
- Difference in the number of hospitalisations due to asthma exacerbation between treatment arms(Baseline to Day 99)