Clinical trial NCT03851250: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Asthma
Keywords: MRx-4DP0004
Asthma
Live Biotherapeutic Product
Lead sponsor: 4D pharma plc
Sponsor class: INDUSTRY
First posted: 2019-02-22
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of participants in each treatment arm experiencing adverse events
timeFrame: Baseline to Day 127
measure: Number of clinically relevant adverse changes in clinical laboratory tests in each treatment arm
timeFrame: Baseline to Day 127
measure: Number of clinically relevant adverse changes in vital signs in each treatment arm
timeFrame: Baseline to Day 127
measure: Number of clinically relevant adverse changes in 12-lead ECGs in each treatment arm
timeFrame: Baseline to Day 127
Secondary outcomes:
measure: Difference in the mean change in the Asthma Control Questionnaire (ACQ-6) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the number of subjects achieving good asthma control (as defined by an ACQ-6 score <1.0) between treatment arms.
timeFrame: Baseline to Day 99
measure: Difference in the number of asthma exacerbations between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the number of hospitalisations due to asthma exacerbation between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in Forced Expiratory Volume in 1 second (FEV1) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in Peak Expiratory Flow (PEF) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in Forced Vital Capacity (FVC) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in blood eosinophils between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in blood neutrophils between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in use of short-acting beta agonists (SABAs) between treatment arms
timeFrame: 7 period prior to baseline to 7 day period prior to Day 99
measure: Difference in the mean change from baseline in the Asthma Quality of Life Questionnaire (standardised version) (AQLQ(S)) between treatment arms
timeFrame: Baseline to Day 99
Other outcomes:
measure: Difference in the change from baseline in faecal microbiota profile between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in Fraction exhaled nitric oxide (FeNO) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in Immunoglobulin E (IgE) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in leukotriene E4 between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in peripheral blood mononuclear cells (PBMCs) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in serum cytokines between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in sputum eosinophils (percentage count) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in sputum eosinophils (absolute count) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in sputum neutrophils (percentage count) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in sputum neutrophils (absolute count) between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in sputum microbiota profile between treatment groups
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in sputum cytokine profile between treatment arms
timeFrame: Baseline to Day 99
measure: Difference in the change from baseline in urine metabolomics profile between treatment arms
timeFrame: Baseline to Day 99
Locations:
city: Portland
country: United States
facility: OHSU Allergy and Clinical Immunology Clinic
state: Oregon
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospital
state: West Yorkshire
city: Leicester
country: United Kingdom
facility: 4D Site Leicester
city: Manchester
country: United Kingdom
facility: 4D Site Manchester
Study officials:
affiliation: University of Leicester
name: Christopher Brightling, Professor
role: PRINCIPAL_INVESTIGATOR
References: