Asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Code: MRx-4DP0004
Pharmaceutical Form: Capsule
INN or Proposed INN: Bifidobacterium breve
Current Sponsor code: MRx-4DP0004
Othe
Sponsors
4D pharma plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent. 2. Participants with a documented medical history and diagnosis of asthma at least 6 months prior to Visit 1. 3. Participants who have stable current treatment as per GINA treatment steps 2 to 4 (ICS with or without LABA) for the past 2 months at least. 4. Participants who have an ACQ-6 score =1.5 and =4 at screening (V0), =1.0 and =4 at baseline (V2). 5. Participants who have FEV1 >50% of predicted normal. 6. Male and female participants are eligible to enter provided the following criteria regarding contraception, pregnancy and breast feeding are met. Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: • Not a woman of childbearing potential (WOCBP) OR • A WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 2 menstrual periods after the last dose. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Are non-compliant with prescribed asthma maintenance therapy in the opinion of the Investigator. 2. Are at significant risk of being exposed to a change in environmental sensitising substances during the duration of the study (e.g., start or end of pollen season, exposure to sensitising animals etc.) according to Investigator’s judgement. 3. Co-morbidities that have not been optimally controlled for the last 3 months. Any significant disease or disorder (e.g., cardiovascular, pulmonary other than asthma, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the participant at risk because of inclusion in the study, or may influence the results of the study, or the participant’s ability to enter the study. 4. Have human immunodeficiency virus (HIV) or active hepatitis B or hepatitis C. 5. Participants with known GI fistula, feeding tubes or inflammatory bowel disease. 6. Participants with GI disease resulting in an inability to take oral medication, malabsorption syndrome, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn’s, ulcerative colitis). 7. Medical history of life-threatening asthma including intubation and intensive care unit admission. 8. Participants who use systemic corticosteroids for any reason within 6 weeks of first dose of IMP. 9. Participants who are allergic to all the following 3 antibiotics: ampicillin, clindamycin, imipenem. 10. Participants using probiotic supplements (probiotic yoghurts are allowed). 11. Participants who are immunosuppressed or receiving immunosuppressant medication. 12. Participants using ICS - LABA combination as both Maintenance And Reliever Therapy (MART regimen). 13. Current smokers or nicotine users in any form including e-cigarettes and nicotine patches or sprays or participants who have smoked/used nicotine in the 3 months prior to Screening. 14. Former smokers with >15 pack years. 15. Participants who have completed a course of systemic antibiotics in the 4 weeks prior to first dose of IMP. 16. Participants with clinically significant abnormal, in the opinion of the Investigator, values for haematology and serum biochemistry results at Screening. 17. Participants who have a known sensitivity to any of the constituents of the IMP. 18. Diastolic blood pressure 90 mmHg, systolic blood pressure 155 mmHg, and/or a pulse rate 100 beats per minute (bpm) after resting for 5 minutes. 19. Participants with clinically significantly abnormal ECGs or structural cardiac abnormalities e.g. structural or valvular heart defects, patent foramen ovale. 20. Any condition that, in the opinion of the Investigator, might interfere with the primary study objective.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine safety and tolerability of 12 weeks of dosing with MRx-4DP0004 given in addition to long-term treatment with ICS with or without LABA in participants who have asthma.; Secondary Objective: Secondary: • To demonstrate improvement in asthma in response to treatment as measured by ACQ-6 score, number of exacerbations and of hospitalisations due to exacerbations. • To assess change from baseline in respect of FEV1, PEF and FVC. • To assess changes in eosinophil and neutrophil counts, the use of SABAs and in the AQLQ(S). Exploratory: • To assess changes in faecal microbiota and urine metabolomics. • To identify possible surrogate biomarkers of efficacy of MRx-4DP0004 in participants with partially controlled asthma, for assessment in future studies. • To assess changes from baseline in T Cell function. • To assess changes in sera cytokine concentrations. Additional UK sample objectives: • To assess changes in induced sputum eosinophil and neutrophil counts. • To assess changes in sputum microbiota. • To assess changes in sputum cytokine profile. ;Primary end point(s): The primary endpoint/outcomes are the number of participants experiencing AEs and SAEs in each treatment arm, clinically relevant adverse changes in laboratory, spirometry, vital signs, and ECG parameters.;Timepoint(s) of evaluation of this end point: Every study visit from Visit 0 (Day -13 to 0) up to and including Visit 7 (Day 127) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints/outcomes: • Mean change from baseline in ACQ-6 score at Day 99. • Participants who have an ACQ-6 score of <1.0 at Day 99. • Participants who experience an exacerbation of their asthma • Participants who are hospitalised due to an exacerbation of their asthma • Change from baseline in participants’ FEV1 at Day 99. • Change from baseline in participants’ PEF at Day 99. • Change from baseline in participants’ FVC at Day 99. • Change from baseline in eosinophil and neutrophil counts (percentage and absolute) at Day 99. • Change from baseline (7-day period before dosing) in participants’ use of SABA during the 7-day period before Day 99. • Change from baseline score of at least 0.5 in AQLQ(S) at Day 99. Exploratory endpoints/outcomes are: • Faecal microbiota and urine metabolomics. • Participants FeNO concentrations. • Change in participant’s serum IgE concentration. • Participants urinary Leukotriene E4 concentration. • Change from baseline in T Cell function at Day 99. • Change in concentrations of cytokines in participants’ sera. Additional UK sample endpoints/outcomes are: • Change from baseline in induced sputum eosinophil and neutrophil counts (percentage and absolute) at Day 99. • Participant sputum microbiota. • Participant sputum cytokine profile. ; Timepoint(s) of evaluation of this end point: Secondary: • ACQ-6: every visit (Visits 0 to 7) • Asthma exacerbation: ongoing AE collection • FEV1, PEF & FVC: every visit (Visits 0 to 7) • Eosinophils & neutrophils: Visit 0 & | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Department
4D pharma plc
Outcome results
None listed