A Study of MRx-4DP0004 in Asthma

NCT03851250 | Terminated Phase 1 FDA Drug

• 1 other identifier: MRx-4DP0004-I-001
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 4

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.

Conditions

Asthma

Keywords

MRx-4DP0004; Asthma; Live Biotherapeutic Product

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (11)

• Difference in the mean change in the Asthma Control Questionnaire (ACQ-6) between treatment arms

  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.

  Baseline to Day 99

• Difference in the number of asthma exacerbations between treatment arms

  Baseline to Day 99

• Difference in the number of hospitalisations due to asthma exacerbation between treatment arms

  Baseline to Day 99

• Difference in the change from baseline in Forced Expiratory Volume in 1 second (FEV1) between treatment arms

  Baseline to Day 99

Other Outcomes (13)

• Difference in the change from baseline in faecal microbiota profile between treatment arms

  Baseline to Day 99

• Difference in the change from baseline in Fraction exhaled nitric oxide (FeNO) between treatment arms

  Baseline to Day 99

• Difference in the change from baseline in Immunoglobulin E (IgE) between treatment arms

  Baseline to Day 99

Study Arms (2)

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.

Drug: MRx-4DP0004

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.

Drug: Placebo

Interventions

MRx-4DP0004 DRUG

Participants randomised to receive MRx-4DP0004 will take it in addition to their regular asthma medication.

MRx-4DP0004

Placebo DRUG

Participants randomised to receive placebo will take it in addition to their regular asthma medication.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• 4D pharma plc: lead

Study Sites (4)

OHSU Allergy and Clinical Immunology Clinic

Portland, Oregon, 97239, United States

Location

Bradford Teaching Hospital

Bradford, West Yorkshire, United Kingdom

Location

4D Site Leicester

Leicester, United Kingdom

Location

4D Site Manchester

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Christopher Brightling, Professor

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: February 22, 2019
• Study Start: July 4, 2019
• Primary Completion: April 26, 2023
• Study Completion: April 26, 2023
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); US (1)