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Trial registered on ANZCTR


Registration number
ACTRN12623000291684
Ethics application status
Approved
Date submitted
24/02/2023
Date registered
17/03/2023
Date last updated
7/04/2024
Date data sharing statement initially provided
17/03/2023
Date results information initially provided
30/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety, tolerability and pharmacokinetics of MAP 315 in healthy adults
Scientific title
A phase 1, randomised, double-blind, placebo-controlled, study to evaluate the safety, tolerability and pharmacokinetics of MAP 315 in healthy adults
Secondary ID [1] 308964 0
MAP315-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative colitis 328980 0
Condition category
Condition code
Oral and Gastrointestinal 325963 325963 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 325410 0
Treatment: Drugs
Comparator / control treatment
This study is placebo controlled. The placebo capsules are matched in appearance to the active MAP 315 intervention and contain the same excipient ingredients.
The Placebo capsules will be administered in the same manner and following the same timing as the active drug.
-Cohort 1 will receive one placebo capsule administered orally daily in the morning (before 12 noon) for 14 consecutive days.
-Cohort 2 will receive four placebo capsules administered orally in the morning (before 12 noon) and 4 capsules administered orally in the evening (10 to 14 hours after the morning does) for a total of 8 capsules a day for 14 consecutive days.
Control group
Placebo

Outcomes
Primary outcome [1] 333809 0
To evaluate the safety and tolerability of MAP 315 when administered to healthy adult participants.
Safety and tolerability of MAP 315 will be assessed by the incidence, nature and severity of all adverse events (AEs) and serious adverse events (SAEs) during the study period. AEs will be coded using the most current Medical Dictionary for Regulatory Activities (MedDRA) available at the commencement of the trial. There are no known adverse events for MPA 315 but possible adverse events may include gastrointestinal discomfort.

Safety during the study period will also be assessed based on data from:
-Clinical laboratory safety analyses (haematology, coagulation, clinical chemistry, and urinalysis)
-Vital signs: heart rate, respiratory rate is measured manually by the medical staff using clock; systolic and diastolic blood pressure (SBP and DBP) using sphygmomanometer; and body temperature is measured using tympanic thermometer
-heart function measured using 12-lead-electrocardiogram (ECG)
-Physical examination includes weight is measured weighing scales, general observations, skin examination, lymph nodes examination, examination of the head, eyes, ears, nose, throat, and extremities, examinations of cardiac system, lungs/respiratory system, abdominal (focusing on liver and spleen).
Timepoint [1] 333809 0
AEs and SAEs will be assessed from the time the participant signs the consent form until Day 28 post-dose.
Safety assessments are collected on Day -1 , pre-dose Day 1, Day 2, Day 3, Day 7, Day 14 and Day 28. All assessments scheduled for Day 2, Day3, Day 7 and Day 14 will be conducted before morning dosing of the visit day.
Secondary outcome [1] 418370 0
To assess potential translocation of MAP 315 to the bloodstream. The incidence and concentration of MAP 315 in serum will be measured using a quantitative polymerase chain reaction technique (qPCR).
Timepoint [1] 418370 0
Blood sampling for the measurement of bacterial translocation will be collected on Day -1, Day 7 (before morning dosing), Day 14 (before morning dosing) and Day 28.
Secondary outcome [2] 418371 0
To characterise the pharmacokinetic profile (PK) of the MAP 315. The concentration of MAP 315 in faecal samples will be measured using qPCR.
Timepoint [2] 418371 0
Faecal sample collection for PK profile will occur on:
-Day -1 and can be collected up until morning dose on Day 1
-Day 1 and Day 3- any time after the administration of the morning dose
-Day 7, Day 14, Day 28- may be collected the day before the visit day or any time during the visit day

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
13/06/2023
Actual
26/06/2023
Date of last participant enrolment
Anticipated
30/06/2023
Actual
9/08/2023
Date of last data collection
Anticipated
5/09/2023
Actual
28/09/2023
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24004 0
Nucleus Network - Melbourne
Recruitment hospital [2] 24113 0
Nucleus Network - Geelong
Recruitment postcode(s) [1] 39491 0
3004 - Melbourne
Recruitment postcode(s) [2] 39621 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 313177 0
Commercial sector/Industry
Name [1] 313177 0
Microba Pty Ltd
Country [1] 313177 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Microba Pty Ltd
Address
Level 10, 388 Queen St
Brisbane, Queensland, 4000
Country
Australia
Secondary sponsor category [1] 314886 0
Commercial sector/Industry
Name [1] 314886 0
Beyond Drug Development Pty Ltd
Address [1] 314886 0
17 Brereton St
South Brisbane QLD 4101
Country [1] 314886 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312415 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 312415 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 312415 0
Australia
Date submitted for ethics approval [1] 312415 0
20/02/2023
Approval date [1] 312415 0
29/03/2023
Ethics approval number [1] 312415 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes
The participant must not have a positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease of 2019 [COVID]-19) within 7 days of admission to the clinical trial unit (CRU).
Note: A nose and/or throat swab or saliva sample may be collected and analysed for
COVID-19 at any visits during the study as per local, state and national guidelines and
requirements at the CRU.
Eligible participants must have received at least 2 vaccinations against COVID-19 (double
vaccination).

Contacts
Principal investigator
Name 124578 0
Dr Sam Francis
Address 124578 0
Nucleus Network
Level 5, Burnet Tower
89 Commercial Road
Melbourne, Victoria, 3004
Country 124578 0
Australia
Phone 124578 0
+61 466 640 801
Fax 124578 0
Email 124578 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 124579 0
Mr Nucleus Network
Address 124579 0
Nucleus Network
Level 5, Burnet Tower
89 Commercial Road
Melbourne, Victoria, 3004
Country 124579 0
Australia
Phone 124579 0
+61 466 640 801
Fax 124579 0
Email 124579 0
s.francis@nucleusnetwork.com.au
Contact person for scientific queries
Name 124580 0
Prof Trent Munro
Address 124580 0
Microba Level 10, 324 Queen Street, Brisbane, QLD, 4000, Australia
Country 124580 0
Australia
Phone 124580 0
+611300974621
Fax 124580 0
Email 124580 0
info@microba.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.