A Study of MRx-4DP0004 in Asthma

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: MRx-4DP0004
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history and diagnosis of asthma at least 6 months prior to Visit 1. Stable current asthma treatment as per GINA steps 2-4 (ICS with or without LABA) for at least 2 months prior to Visit 1. ACQ-6 score >1.5 and <=4 FEV1 >50% of predicted normal Following protocol specified contraception requirements. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRx-4DP0004<br>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. | Drug: MRx-4DP0004<br>* Participants randomised to receive MRx-4DP0004 will take it in addition to their regular asthma medication.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Participants randomised to receive placebo will take it in addition to their regular asthma medication.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants in each treatment arm experiencing adverse events | Adverse events will be considered alongside other primary outcome measures for assessment of safety and tolerability. | Baseline to Day 127 | 
| Number of clinically relevant adverse changes in clinical laboratory tests in each treatment arm | 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. | Baseline to Day 127 | 
| Number of clinically relevant adverse changes in vital signs in each treatment arm | 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. | Baseline to Day 127 | 
| Number of clinically relevant adverse changes in 12-lead ECGs in each treatment arm | 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. | Baseline to Day 127 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the mean change in the Asthma Control Questionnaire (ACQ-6) between treatment arms | The ACQ-6 consists of 6 questions relating to control of asthma symptoms answered on a 7 point scale. The overall score is the mean of the 6 questions and is rated from 0 (totally controlled) to 6 (severely uncontrolled). | 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. | The ACQ-6 consists of 6 questions relating to control of asthma symptoms answered on a 7 point scale. The overall score is the mean of the 6 questions and is rated from 0 (totally controlled) to 6 (severely uncontrolled). | Baseline to Day 99 | 
| Difference in the number of asthma exacerbations between treatment arms | To determine if MRx-4DP0004 can reduce the number of asthma exacerbations, the number of participants experiencing an exacerbation will be assessed. | Baseline to Day 99 | 
| Difference in the number of hospitalisations due to asthma exacerbation between treatment arms | To determine if MRx-4DP0004 can reduce the number of hospitalisations due to exacerbation of asthma symptoms, the number of participants who are hospitalised due to an exacerbation will be assessed. | Baseline to Day 99 | 
| Difference in the change from baseline in Forced Expiratory Volume in 1 second (FEV1) between treatment arms | To assess the response to MRx-4DP0004 in respect of changes to FEV1, the change from baseline in FEV1 will be assessed. | Baseline to Day 99 | 
| Difference in the change from baseline in Peak Expiratory Flow (PEF) between treatment arms | To assess the response to MRx-4DP0004 in respect of changes to PEF, the change from baseline in PEF will be assessed. | Baseline to Day 99 | 
| Difference in the change from baseline in Forced Vital Capacity (FVC) between treatment arms | To assess the response to MRx-4DP0004 in respect of changes to FVC, the change from baseline in FVC will be assessed. | Baseline to Day 99 | 
| Difference in the change from baseline in blood eosinophils between treatment arms | To assess the effect of MRx-4DP0004 on levels of eosinophils in blood, the change from baseline in percentage and absolute eosinophil counts will be assessed. | Baseline to Day 99 | 
| Difference in the change from baseline in blood neutrophils between treatment arms | To assess the effect of MRx-4DP0004 on levels of neutrophils in blood, the change from baseline in percentage and absolute neutrophil counts will be assessed. | Baseline to Day 99 | 
| Difference in the change from baseline in use of short-acting beta agonists (SABAs) between treatment arms | To assess the effect of MRx-4DP0004 on the use of SABAs, the change from baseline in SABA use will be assessed. | 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 | The AQLQ(S) consists of 32 questions relating to quality of life in relation to asthma answered on a 7 point scale. The overall score is the mean of the 32 questions and is rated from 7 (not impaired at all) to 1 (severely impaired). | Baseline to Day 99 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRx-4DP0004, Asthma, Live Biotherapeutic Product