Back to resultsA Study of MRx-4DP0004 in Asthma
Primary Purpose
Asthma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MRx-4DP0004
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring MRx-4DP0004, Asthma, Live Biotherapeutic Product
Eligibility Criteria
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
Sites / Locations
- OHSU Allergy and Clinical Immunology Clinic
- Bradford Teaching Hospital
- 4D Site Leicester
- 4D Site Manchester
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
MRx-4DP0004
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03851250
Brief Title
A Study of MRx-4DP0004 in Asthma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor insolvency
Study Start Date
July 4, 2019 (Actual)
Primary Completion Date
April 26, 2023 (Actual)
Study Completion Date
April 26, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
4D pharma plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
MRx-4DP0004, Asthma, Live Biotherapeutic Product
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MRx-4DP0004
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MRx-4DP0004
Intervention Description
Participants randomised to receive MRx-4DP0004 will take it in addition to their regular asthma medication.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants randomised to receive placebo will take it in addition to their regular asthma medication.
Primary Outcome Measure Information:
Title
Number of participants in each treatment arm experiencing adverse events
Description
Adverse events will be considered alongside other primary outcome measures for assessment of safety and tolerability.
Time Frame
Baseline to Day 127
Title
Number of clinically relevant adverse changes in clinical laboratory tests in each treatment arm
Description
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.
Time Frame
Baseline to Day 127
Title
Number of clinically relevant adverse changes in vital signs in each treatment arm
Description
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.
Time Frame
Baseline to Day 127
Title
Number of clinically relevant adverse changes in 12-lead ECGs in each treatment arm
Description
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.
Time Frame
Baseline to Day 127
Secondary Outcome Measure Information:
Title
Difference in the mean change in the Asthma Control Questionnaire (ACQ-6) between treatment arms
Description
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).
Time Frame
Baseline to Day 99
Title
Difference in the number of subjects achieving good asthma control (as defined by an ACQ-6 score <1.0) between treatment arms.
Description
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).
Time Frame
Baseline to Day 99
Title
Difference in the number of asthma exacerbations between treatment arms
Description
To determine if MRx-4DP0004 can reduce the number of asthma exacerbations, the number of participants experiencing an exacerbation will be assessed.
Time Frame
Baseline to Day 99
Title
Difference in the number of hospitalisations due to asthma exacerbation between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in Forced Expiratory Volume in 1 second (FEV1) between treatment arms
Description
To assess the response to MRx-4DP0004 in respect of changes to FEV1, the change from baseline in FEV1 will be assessed.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in Peak Expiratory Flow (PEF) between treatment arms
Description
To assess the response to MRx-4DP0004 in respect of changes to PEF, the change from baseline in PEF will be assessed.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in Forced Vital Capacity (FVC) between treatment arms
Description
To assess the response to MRx-4DP0004 in respect of changes to FVC, the change from baseline in FVC will be assessed.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in blood eosinophils between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in blood neutrophils between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in use of short-acting beta agonists (SABAs) between treatment arms
Description
To assess the effect of MRx-4DP0004 on the use of SABAs, the change from baseline in SABA use will be assessed.
Time Frame
7 period prior to baseline to 7 day period prior to Day 99
Title
Difference in the mean change from baseline in the Asthma Quality of Life Questionnaire (standardised version) (AQLQ(S)) between treatment arms
Description
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).
Time Frame
Baseline to Day 99
Other Pre-specified Outcome Measures:
Title
Difference in the change from baseline in faecal microbiota profile between treatment arms
Description
Faecal samples will be analysed using the MicroDx (R) platform.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in Fraction exhaled nitric oxide (FeNO) between treatment arms
Description
Changes in participants FeNO concentrations will be assessed over the course of the study.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in Immunoglobulin E (IgE) between treatment arms
Description
Changes in participants serum IgE levels will be assessed over the course of the study.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in leukotriene E4 between treatment arms
Description
Changes in participants urinary leukotriene E4 levels will be assessed over the course of the study.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in peripheral blood mononuclear cells (PBMCs) between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in serum cytokines between treatment arms
Description
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
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in sputum eosinophils (percentage count) between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in sputum eosinophils (absolute count) between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in sputum neutrophils (percentage count) between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in sputum neutrophils (absolute count) between treatment arms
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in sputum microbiota profile between treatment groups
Description
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.
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in sputum cytokine profile between treatment arms
Description
To assess the effect of MRx-4DP0004 on induced sputum cytokines, changes from baseline in sputum cytokines will be assessed
Time Frame
Baseline to Day 99
Title
Difference in the change from baseline in urine metabolomics profile between treatment arms
Description
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
Time Frame
Baseline to Day 99
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Brightling, Professor
Organizational Affiliation
University of Leicester
Official's Role
Principal Investigator
Facility Information:
Facility Name
OHSU Allergy and Clinical Immunology Clinic
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Bradford Teaching Hospital
City
Bradford
State/Province
West Yorkshire
Country
United Kingdom
Facility Name
4D Site Leicester
City
Leicester
Country
United Kingdom
Facility Name
4D Site Manchester
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of MRx-4DP0004 in Asthma
We'll reach out to this number within 24 hrs