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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MRx-4DP0004 | Experimental | 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. |
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| Placebo | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MRx-4DP0004 | Drug | Participants randomised to receive MRx-4DP0004 will take it in addition to their regular asthma medication. |
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| 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 |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Brightling, Professor | University of Leicester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| OHSU Allergy and Clinical Immunology Clinic | Portland | Oregon | 97239 | United States | ||
| Bradford Teaching Hospital |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| Placebo | Drug | Participants randomised to receive placebo will take it in addition to their regular asthma medication. |
|
| 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 |
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 |
| Bradford |
| West Yorkshire |
| United Kingdom |
| 4D Site Leicester | Leicester | United Kingdom |
| 4D Site Manchester | Manchester | United Kingdom |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |