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

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)

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19
• Intervention / Treatment: Drug: MRx-4DP0004; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Plymouth, United Kingdom
    • University Hospitals Plymouth NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to sign the consent form

• Suspected or confirmed COVID-19 as defined by:

  1. Positive RNA test for SARS-CoV-2 OR
  2. Presenting with symptoms of COVID-19 as determined by the investigator, and
  3. A score of 4 or 5 on the WHO Ordinal Scale for Clinical Improvement, and
  4. Oxygen saturation of <95% on room air, and
  5. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MRx-4DP0004; 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; MRx-4DP0004 is a lyophilised formulation of a proprietary strain of bacteria.
PLACEBO_COMPARATOR: Placebo; Patients receiving standard of care will also take 2 placebo capsules, twice a day for 14 days.	Drug: Placebo; Placebo capsules will be identical in appearance to active product.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 4D pharma plc
• Investigators: Principal Investigator: Dinesh Saralaya, MBBS, MD, MRCP, FRCP, Bradford Royal Infirmary

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2020
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): January 1, 2021

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (ACTUAL): April 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 16, 2021
• Last Update Submitted That Met QC Criteria: June 11, 2021
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; Immunomodulatory; Live Biotherapeutic Product; MRx-4DP0004
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: MRx-4DP0004-II-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No