A Study of MRx-4DP0004 in Asthma

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

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: MRx-4DP0004; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • 4D Site Leicester
  • Manchester, United Kingdom
    • 4D Site Manchester
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom
      • Bradford Teaching Hospital
• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Allergy and Clinical Immunology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the change from baseline in faecal microbiota profile between treatment arms	Faecal samples will be analysed using the MicroDx (R) platform.	Baseline to Day 99
Difference in the change from baseline in Fraction exhaled nitric oxide (FeNO) between treatment arms	Changes in participants FeNO concentrations will be assessed over the course of the study.	Baseline to Day 99
Difference in the change from baseline in Immunoglobulin E (IgE) between treatment arms	Changes in participants serum IgE levels will be assessed over the course of the study.	Baseline to Day 99
Difference in the change from baseline in leukotriene E4 between treatment arms	Changes in participants urinary leukotriene E4 levels will be assessed over the course of the study.	Baseline to Day 99
Difference in the change from baseline in peripheral blood mononuclear cells (PBMCs) between treatment arms	To assess the effect of MRx-4DP0004 on PBMCs, changes from baseline in lymphocytes and monocytes will be assessed through measurement of CD3, CD16+56, CD45, CD4, CD19, CD8, CD14, CD15, CD16 and CD64.	Baseline to Day 99
Difference in the change from baseline in serum cytokines between treatment arms	To assess the effect of MRx-4DP0004 on serum cytokines, changes from baseline in IL-1a, IL-1b, CXCL1, CXCL2, IL-6, IL-8, IL-17A, IL-5, IL-4, IL-13, CCL11/eotaxin and TSLP will be assessed	Baseline to Day 99
Difference in the change from baseline in sputum eosinophils (percentage count) between treatment arms	To assess the effect of MRx-4DP0004 on levels of eosinophils in induced sputum, changes form baseline in percentage eosinophil count will be assessed for participants in the UK only.	Baseline to Day 99
Difference in the change from baseline in sputum eosinophils (absolute count) between treatment arms	To assess the effect of MRx-4DP0004 on levels of eosinophils in induced sputum, changes form baseline in absolute eosinophil count will be assessed for participants in the UK only.	Baseline to Day 99
Difference in the change from baseline in sputum neutrophils (percentage count) between treatment arms	To assess the effect of MRx-4DP0004 on levels of neutrophils in induced sputum, changes form baseline in percentage neutrophil count will be assessed for participants in the UK only.	Baseline to Day 99
Difference in the change from baseline in sputum neutrophils (absolute count) between treatment arms	To assess the effect of MRx-4DP0004 on levels of neutrophils in induced sputum, changes form baseline in absolute neutrophil count will be assessed for participants in the UK only.	Baseline to Day 99
Difference in the change from baseline in sputum microbiota profile between treatment groups	To assess the effect of MRx-4DP0004 on induced sputum microbiota, changes from baseline in sputum microbiota will be assessed. Sputum samples will be analysed using the MicroDx (R) platform.	Baseline to Day 99
Difference in the change from baseline in sputum cytokine profile between treatment arms	To assess the effect of MRx-4DP0004 on induced sputum cytokines, changes from baseline in sputum cytokines will be assessed	Baseline to Day 99
Difference in the change from baseline in urine metabolomics profile between treatment arms	To assess the effect of MRx-4DP0004 on urine metabolomics, the change from baseline in urine metabolomics will be assessed. Urine samples will be analysed using the MicroDx (R) platform	Baseline to Day 99

Collaborators and Investigators

• Sponsor: 4D pharma plc
• Investigators: Principal Investigator: Christopher Brightling, Professor, University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2019
• Primary Completion (Actual): April 26, 2023
• Study Completion (Actual): April 26, 2023

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 22, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Asthma; Live Biotherapeutic Product; MRx-4DP0004
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: MRx-4DP0004-I-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: Yes
• Studies a U.S. FDA-regulated device product: No