A Study for Efficacy and Safety of Live Biotherapeutic MRx4DP0004 to Treat COVID-19

Study Overview
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Brief Summary
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This is a randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of MRx-4DP0004 in patients with COVID-19. 90 hospitalised patients will be enrolled and randomised (2:1) to receive MRx-4DP0004 or placebo for up to 14 days. MRx-4DP0004 is an immunomodulating Live Biotherapeutic Product (LBP) which is expected to prevent or reduce the hyperinflammatory response to SARS-CoV-2 infection without impairing viral clearance.

Official Title
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A Pilot, Multiple Dose Study to Evaluate the Efficacy and Safety of MRx-4DP0004 in Hospitalised Patients With Symptoms of COVID-19 (SARS-CoV-2 Infection)

Conditions
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COVID-19

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: Willing and able to sign the consent form Suspected or confirmed COVID-19 as defined by: Positive RNA test for SARS-CoV-2 OR Presenting with symptoms of COVID-19 as determined by the investigator, and A score of 4 or 5 on the WHO Ordinal Scale for Clinical Improvement, and Oxygen saturation of <95% on room air, and Chest X-ray with evidence of COVID-19 e.g. ground-glass opacities Requires admission to hospital Able to swallow oral capsules Exclusion Criteria: Known valvular heart defects, pulmonary hypertension or heart failure Known to have cystic fibrosis GI fistula or malabsorption syndrome Known allergy to ampicillin, clindamycin and imipenem Any other condition which, in the opinion of the investigator, would prevent full participation in the study or would interfere with the evaluation of the study endpoints Antibiotic treatment at enrolment or within 2 days prior Pregnant or breastfeeding females Unable or unwilling to follow contraception requirements Concurrent participation in another interventional clinical trial at enrolment or within 30 days prior

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRx-4DP0004<br>Patients receiving standard of care will add MRx-4DP0004 to their treatment. MRx-4DP0004 is taken as 2 capsules, twice a day for 14 days. Daily dose is 4 x 10^9 to 4 x10^10 colony forming units. | Drug: MRx-4DP0004<br>* MRx-4DP0004 is a lyophilised formulation of a proprietary strain of bacteria.<br>|
| Placebo Comparator: Placebo<br>Patients receiving standard of care will also take 2 placebo capsules, twice a day for 14 days. | Drug: Placebo<br>* Placebo capsules will be identical in appearance to active product.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean clinical status score in each treatment arm | Clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement where patients are scored on a scale of 0-8 with 0 being uninfected and 8 being dead | Baseline to Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events in each treatment arm | Safety and tolerability will be determined according to clinically relevant reported adverse events | Baseline to Day 42 | 
| Number of patients with an improvement in clinical status score in each treatment arm | Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement | Day 1 to Day 42 | 
| Number of patients with a deterioration in clinical status score in each treatment arm | Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement | Day 1 to Day 42 | 
| Number of patients with at least 95% oxygen saturation on room air in each treatment arm | Oxygen saturation will be measured as per local standard procedures | Day 1 to Day 14 | 
| Time to patients with at least 95% oxygen saturation on room air in each treatment arm | Oxygen saturation will be recorded daily during hospitalisation to determine the mean time for each arm to reach at least 95% saturation | Day 1 to Day 14 | 
| Number of patients with an improvement in the National Early Warning Score (NEWS) 2 in each treatment arm | The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature | Day 1 to Day 14 | 
| Number of patients with an deterioration in the National Early Warning Score (NEWS) 2 in each treatment arm | The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature | Day 1 to Day 14 | 
| Number of patients requiring Continuous Positive Airway Pressure in each treatment arm | Details of required respiratory support will be recorded throughout hospitalisation | Day 1 to Day 14 | 
| Number of patients requiring Intermittent Positive Pressure Ventilation in each treatment arm | Details of required respiratory support will be recorded throughout the treatment period | Day 1 to Day 14 | 
| Time to patients requiring Continuous Positive Airway Pressure in each treatment arm | Details of required respiratory support will be recorded throughout the treatment period | Day 1 to Day 14 | 
| Time to patients requiring Intermittent Positive Pressure Ventilation in each treatment arm | Details of required respiratory support will be recorded throughout the treatment period | Day 1 to Day 14 | 
| Time to discharge in each treatment arm | Length of hospital stay will be compared | Day 1 to Day 42 | 
| Number of deaths in each treatment arm | All cause mortality will be compared | Day 1 to Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRx-4DP0004, Coronavirus, Live Biotherapeutic Product, SARS-CoV-2, Immunomodulatory