None listed
Conditions
Brief summary
This is a first in human study for MAP 315 designed to investigate the safety, tolerability and pharmacokinetics of multiple doses of MAP 315 in healthy adult volunteers. The pharmacodynamic effects of MAP315 will also be explored. The active ingredient of MAP 315 is a live bacterium that is a common member of the gut microbiome of healthy adults. MAP315 is being developed for the treatment of Ulcerative colitis. It is a randomised, double-blind and placebo-controlled study conducted at a single clinical trial centre with a satellite site as an alternate location for screening and outpatient assessments. The study will enroll 2 cohorts of 16 participants each, who will be randomised 3:1 to receive MAP 315 (4 x 10^7 CFU of MAP 315 per capsule) or its matching placebo for 14 consecutive days (2 weeks). The first Cohort will receive one capsule of MAP 315 (4 x 10^7 CFU of MAP 315 per capsule) or matching placebo daily administered orally for 14 consecutive days, (total daily dose of 4 x 10^7 CFU of MAP 315). Cohort 2 will receive four (4) MAP 315 capsules, twice daily for a total of 8 MAP 315 capsules per day for 14 consecutive days, (a total daily dose of 3.2 x 10^8 CFU of MAP 315). The capsules are administered orally with water and regardless of food. Participants in the study will be confined in the clinical research unit (CRU) from Day -1 until Day 3, when they will be discharged after completion of all CRU-based assessments scheduled for that day, in the absence of clinically significant signals, at the discretion of the Principal Investigator. Both dose level cohorts (Cohort 1 and Cohort 2) will include at least 2 sentinel participants: 1 to receive MAP 315 and 1 to receive placebo. If dosing of the sentinel participants proceeds without clinically significant safety signals up to at least 72 hours (h) following the administration of the initial study drug dose, as determined by the Principal Investigator in consultation with the local Medical Monitor and Sponsor if required), the remaining 14 participants in the cohort can be dosed according to the randomisation schedule. The decision to proceed to Cohort 2 of the study will be dependent upon review of data from all participants in Cohort 1 up to at least 6 days after the beginning of dosing (ie, the Day 7 visit) by a safety monitoring committee (SMC). This will include the review of all safety data and available PK data for at least 12 participants in Cohort 1.
Interventions
MAP 315 is being developed for administration for the treatment of ulcerative colitis. The active ingredient of MAP 315 is a live bacterium that is a common member of the gut microbiome of healthy adults. MAP 315 drug product consists of lyophilised MAP 315 with excipient(s) in an enteric-coated capsule for oral administration.
The study will enroll 2 cohorts of 16 participants each, who will be randomised 3:1 to receive
MAP 315 capsules (4 x 10^7 CFU of MAP 315 per capsule) or placebo capsule
MAP 315 is being developed for administration for the treatment of ulcerative colitis. The active ingredient of MAP 315 is a live bacterium that is a common member of the gut microbiome of healthy adults. MAP 315 drug product consists of lyophilised MAP 315 with excipient(s) in an enteric-coated capsule for oral administration. The study will enroll 2 cohorts of 16 participants each, who will be randomised 3:1 to receive MAP 315 capsules (4 x 10^7 CFU of MAP 315 per capsule) or placebo capsules administered daily in the morning (before 12 noon) for 14 consecutive days. The capsules are administered orally with water and regardless of food. Cohort 1 will receive one capsule of MAP 315 or placebo administered daily in the morning (before 12 noon) for 14 consecutive days (total daily dose of 4 x 10^7 CFU of MAP 315). Cohort 2 will receive four (4) capsules of MAP 315 or placebo administered in the morning (before 12 noon) and 4 capsules administered in the evening (10 to 14 hours after the morning dose) for a total of 8 capsules a day daily for 14 consecutive days (a total daily dose of 3.2 x 10^8 CFU of MAP 315. Each Cohort will be administered to a distinct group of participants and escalation to Cohort 2 will occur only after completion of a review by the safety review committee of at least 6 days post-treatment clinical safety and tolerability findings and available pharmacokinetic data of at least 12 participants in Cohort 1. For both cohorts, the intervention will be administered for the first 3 days at the clinical trial unit (CRU) by trained clinical trial site staff and the following 11 days by self-administered by the participant outside of the CRU. A study diary will be utilised to monitor intervention adherence during the outpatient period (days 4 to 14). Diary entry review will be conducted by site staff at each participant interaction.
Sponsors
Microba Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female participants aged between 18 to 65 years inclusive at Screening. 2. The participants must be in good general health, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, safety laboratory tests and cardiac monitoring at Screening, and/or before administration of the initial dose of the study drug (active or placebo). 3. The participants must weigh greater than or equal to 50 kg and have a body mass index (BMI) between 18 and 32 kg/m2 inclusive at Screening. 4. The participants must agree to abstain from alcohol intake and must agree to not consume poppy seeds from at least 48 hours before the initial administration of the study drug, during all the confinement period, and from at least 48 hours prior to any scheduled site visits. 5. The participant must agree to follow the dietary requirements for the study including not consuming probiotics and/or nutraceuticals from 28 days before initial study drug administration to the end of the study. 6. The participant must agree to continue their normal diet (excluding, as applicable, the limitations required for study participation) from Screening to the end of study visit. 7. The participant must have the ability and willingness to attend the necessary visits to the study centre. 8. The participant must sign a written informed consent prior to undergoing any of the study-specific procedures, including Screening procedures. 9. Male and Female participants must agree to the contraception requirements of the study. Females must be nonpregnant and nonlactating, 10. Women of childbearing potential must have a negative pregnancy test at Screening and admission and be willing to have additional pregnancy tests as required throughout the study. 11. Participants are non-smokers (have last smoked more than 30 days prior to Screening and no longer smoking, or have never smoked), or smoke no more than the equivalent of 5 cigarettes per day since at least 30 days prior to Screening. If users of other nicotine products (ie, spray, patch, e-cigarette) no more than the equivalent of 5 cigarettes per day since at least 30 days prior to Screening is allowed. Subjects must agree to abstain from smoking while in the CRU.
Exclusion criteria
1. The participant has a medical history of or a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) or hepatitis C virus (HCV) antibodies at Screening. 2. The participant is immunocompromised as a result of conditions and/or treatments. 3. The participant has any past or current history of gastrointestinal tract (GIT) and/ or bowel disease. Participants with a history of simple appendectomy and/or cholecystectomy are eligible to be included in the study. 4. The participant has any underlying physical or psychological medical condition that, in the opinion of the Primary Investigator (PI), would make it unlikely for them to complete the study. 5. The participant has evidence of any current chronic medical condition (eg, hypertension, elevated cholesterol/triglycerides, asthma or diabetes, unless as specified in the protocol). 6. The participant uses or is planning to use any anti-inflammatory (with the exception of paracetamol/acetaminophen up to 3000 mg per day), antibiotic, antifungals, acetylsalicylic acid (aspirin) and/or any nonsteroidal anti-inflammatory drugs (NSAIDs) within 28 days prior to the initial study drug administration and/or any other prescription or over-the-counter (OTC) medicines (with the exception of oral contraceptives) within seven days prior to the initial study drug administration, unless in the opinion of the PI, local MM and Sponsor medical representative the medication will not interfere with the study procedures or compromise participant safety. 7. The participant has any clinically significant laboratory abnormality at Screening or on Day -1 per protocol unless not clinically significant at the discretion of the PI. 8. The participant has a history of or current alcoholism or drug abuse within the 1 year prior to the initial study drug administration. Alcohol abuse is defined as greater than 21 standard drinks per week for males, and greater than 14 standard drinks per week for females. 9. The participant has donated blood whole blood (greater than 499 mL), has had a significant blood loss ( greater than 499 mL) within 30 days prior to the initial study drug administration, or has donated plasma within 2 weeks prior to the initial study drug administration. 10. The participant has severe asthma or chronic obstructive pulmonary disease (COPD). Participants with a past history of childhood asthma and/or current history of mild asthma that is anticipated not to require treatment during the study period will be allowed to participate in the study. 11. The participant has been dosed in a clinical trial within 30 days before the initial administration of the study drug; used any experimental therapy within 30 days or 5 half-lives prior to the initial administration of the study drug, whichever is greater; or used any biologic therapy within 12 weeks or 5 half-lives prior to the initial administration of the study drug, whichever is greater. 12. Females who are pregnant or lactating. 13. The participant has had any clinically significant surgery within the 3 months prior to the initial study drug administration that is determined by the PI to have a potential impact on study participation. 14. Participants having received vaccination within 14 days to 28 days (as defined in the protocol) of the anticipated start of the Dosing Period and/or are expected to be vaccinated during the Dosing Period or within 2 weeks postdosing. Or participants have not met vaccination requirements of the study protocol. 15. The participant has an active infection (diagnosed or suspected), and/or history of recurrent infection (local or systemic) within 30 days prior to the initial study drug administration. 16. The participant has any acute illness within 30 days prior to the initial study drug administration. 17. The participant has any known history of severe allergic, anaphylactic, or other hypersensitivity reactions the excipients used in the study drug, or a history of drug or other allergy including severe allergic reaction that in the opinion of the PI, contraindicates their participation. 18. The participant has been judged by the PI to be unfit to participate for any other reason.
Outcome results
None listed