Clinical trial NCT04307173: Study of Multiple Ascending Dose of KBL693 in Healthy Participants
Official title: A Phase I Randomised Double-Blind Placebo-Controlled Study of Multiple Ascending Dose of KBL693 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Moderate to Severe Asthma
Lead sponsor: KoBioLabs
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2020-03-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to investigate the safety and tolerability of KBL693 in healthy volunteers. KBL693 has been developed as a potential new treatment for moderate to severe asthma..

Detailed description: This is a randomized, double-blind, placebo-controlled, single centre Phase I study.

Eighteen (18) subjects are planned to be randomised at 1 site across the 2 parts of the study as follows:

* Cohort 1: 680 mg/day
* Cohort 2: 6800 mg/day

Eligibility criteria: Inclusion Criteria:

1. Healthy volunteers (also referred to as participants) who can read and understand, and are willing to sign the informed consent form
2. Willing and able to comply with clinic visits (including confinement to CTU) and study-related procedures
3. Male or female healthy volunteers aged ≥18 and ≤65 years at Screening
4. Body mass index (BMI) of ≥18.0 kg/m2 to ≤32 kg/m2 (both inclusive) at Screening
5. Normal hemodynamic parameters: systolic blood pressure (BP) ≥90 mmHg and ≤140 mmHg; diastolic BP ≥50 mmHg and ≤90 mmHg; heart rate (HR) ≥40 bpm and ≤100 bpm at Screening and Day -1. Measurements may be repeated up to 3 times at the discretion of the investigator.

   Please note: participants with out of range values, which are not clinically significant as per the principal investigator's (PI) discretion, will be allowed. The PI may delegate this responsibility to a suitably qualified and trained study team member.
6. The participant is, in the opinion of the PI (or delegate), generally healthy based on assessment of medical history, physical examination, vital signs, ECG, and the results of the haematology, clinical chemistry, urinalysis, serology, and other relevant laboratory tests
7. Baseline laboratory test values within reference ranges based on the blood and urine samples taken at Screening and on Day -1. Out of normal ranges values may be accepted by the PI, if not clinically significant
8. Have regular bowel movements (e.g., once daily)
9. Male participants must agree to practise true abstinence; be surgically sterilised (performed at least 6 months prior); or agree to use of a condom if sexually active with a female partner of childbearing potential, from Screening through 90 days after the final dose of the investigational product (IP).
10. Women of child-bearing potential must agree to practise true abstinence or agree to use effective contraception from Screening through 90 days after the final dose of the IP.

    Effective contraception includes:
    1. Oral contraceptives ("the pill") for at least 1 month prior to Day 1, plus use of a condom
    2. Depot or injectable birth control or implantable contraception (e.g., Implanon) plus use of a condom
    3. Intrauterine device plus use of a condom
    4. Vasectomised male partner (performed at least 6 months prior) who has been documented to no longer produce sperm
11. Women of non-child-bearing potential:

    1. Must have documented evidence of surgical sterilization at least 6 months prior to Screening visit e.g., tubal ligation, hysterectomy.
    2. Must be post-menopausal for at least 12 months prior to Screening, as documented by measurement of follicle stimulating hormone level (≥40 mIU/mL).

Exclusion Criteria:

1. Female participants who are pregnant or lactating
2. The participant's corrected QT interval (QTcF) (Fridericia's correction) is \>450 msec (males), and \>470 msec (females) at Screening or on Day -1. An out-of-range or abnormal ECG will be repeated at PI's discretion. In total, 3 ECGs should be recorded consecutively at Screening and on Day -1, and the PI (or delegate) must evaluate the triplicate ECG. If the participant's QTcF is \>450 msec (males) or \>470 msec (females) on at least 2 ECGs or have structural cardiac abnormalities, the participant must be excluded
3. The participant has taken prescription (including antibiotics) or non-prescription medication, herbal remedies, vitamins or minerals, any probiotic drinks and yeast supplements (e.g. Mutaflor®, Bioflor®) within 14 days prior to the first dose of study product unless in the opinion of the PI the medication will not compromise participant safety or interfere with study procedures or data validity. Participant may be rescreened after a washout period of 14 days. Please note use of oral contraceptives and paracetamol up to 2 g/day and/or nonsteroidal anti-inflammatory drugs for symptomatic relief of minor symptoms are allowed
4. Participant has functional GI disorders
5. Participant is a current smoker or has used nicotine containing products within 6 months prior to Screening visit
6. The participant has a substance abuse-related disorder or has a history of drug, alcohol and/or substance abuse deemed significant by the PI
7. The participant has taken any IP within 30 days prior to the first dose of study product or 5 half-lives, whichever is longer
8. The participant has a history of significant hypersensitivity or anaphylaxis involving any drug (including ampicillin, clindamycin or imipenem), any constituent of the IP, food or other precipitating agent (e.g. bee sting). Please note participants with clinically stable mild allergic conditions such as hay fever and mild eczema may be enrolled at the discretion of the PI
9. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus antibody (anti-HCV)at Screening visit.
10. Positive screen for drugs of abuse and cotinine at Screening or on Day -1. Positive screen for alcohol on Day -1.
11. The participant is, in the opinion of the PI, unlikely to comply with the clinical study protocol or is unsuitable for any other reason.

Primary outcomes:
measure: Safety and tolerability measure through Adverse Events/Serious Adverse Events
timeFrame: Measurements at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure
timeFrame: Measurement at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate
timeFrame: Measurement at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- axillary body temperature
timeFrame: Measurement at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- respiratory rate
timeFrame: Measurement at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through 12-lead ECG
timeFrame: Measurement at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Physical exam
timeFrame: Measurement at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Routine Stool Examination
timeFrame: Measurement at Baseline till 28 days
measure: Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Clinical laboratory results
timeFrame: Measurement at Baseline till 28 days
Secondary outcomes:
measure: Difference in the change from baseline in profile of faecal KBL693 between treatment arms
timeFrame: Measurements at Baseline till 28 days
Other outcomes:
Locations:
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
affiliation: Linear Clinical Research
name: Lara Hatchuel, Dr
role: PRINCIPAL_INVESTIGATOR
References: