Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001519741
Ethics application status
Approved
Date submitted
21/11/2022
Date registered
7/12/2022
Date last updated
20/11/2023
Date data sharing statement initially provided
7/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Randomized, Double-blind, Placebo-controlled, First in Human Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of single and multiple doses of MVD1 in healthy adult volunteers
Scientific title
A Phase 1, Randomized, Double-blind, Placebo-controlled, First in Human Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of single and multiple doses of MVD1 in healthy adult volunteers
Secondary ID [1] 307921 0
MVD1-AU-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 327574 0
Metabolic Disorders 328321 0
Condition category
Condition code
Diet and Nutrition 324660 324660 0 0
Obesity
Metabolic and Endocrine 325206 325206 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, randomised, double-blind, placebo-controlled, first in Human study of the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of MVD1 in healthy adult volunteers.
The study will be conducted in 2 parts:

Part A: A single ascending dose (SAD) - Healthy adult males and females 18 to 60 years of age at the time of screening with a body mass index (BMI) between 20 and 32 kg/m2 inclusive; 18 participants will be enrolled across a total of 4 cohorts (6 participants/cohort) corresponding to cohorts S1-S3.

Part B: A multiple ascending dose (MAD) - Healthy obese adult males and females 25 to 60 years of age at the time of screening with a BMI between 28 and 35 kg/m2; 24 participants will be enrolled across a total of 3 cohorts (8 participants/cohort) corresponding to cohorts M1-M3.

MVD1 will be orally administered at the following dose levels:
Part A (SAD): (once only on Day 1)
• Cohort S1: 200 mg
• Cohort S2: 400 mg
• Cohort S3: 800 mg

Part B (MAD): Will be administered orally as twice daily oral doses (Daily oral dose to be administered twice daily on Days 1 to 14 and a final single dose on Day 15).
• Cohort M1: 200 mg
• Cohort M2: 300 mg
• Cohort M3: 400 mg

Dose levels and frequency of dosing to be investigated in Part B may be adjusted based on safety and tolerability and PK data from Part A.

Clinical facility staff will administer the study drug only to participants included in this study following the procedures set out in this study protocol. Administration of study drugs will be recorded in the appropriate drug accountability records and the eCRF. Administration of study drug will be verified by a second staff member. Each participant will be given only the study drug preparation carrying his/her study number.
Intervention code [1] 324382 0
Treatment: Drugs
Comparator / control treatment
Placebo capsules will contain the same amount of microcrystalline cellulose to the corresponding cohort’s planned dosage in a size 0 or size 000 capsule. Placebo capsule will be identical in appearance to MVD1 capsules and administered orally.
Control group
Placebo

Outcomes
Primary outcome [1] 332475 0
To assess the safety and tolerability of a single ascending oral dose of MVD1 in healthy volunteers.

Safety endpoints as change from baseline and where appropriate overtime and versus placebo include:
• Incidence, severity, and relationship of adverse events (AEs)/serious AEs (SAEs) (including withdrawals due to AEs)
• Change in vital signs
• Change in electrocardiogram (ECG) parameters
• Change in clinical laboratory parameters (haematology, serum chemistry, coagulation, and urinalysis)
Timepoint [1] 332475 0
Adverse Events: Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) Version 5). AEs will be assessed continuously as they are reported or observed and reviewed daily on Day -1 (Check-in), Day 1, Day 2, Day 3, Day 4 (Check-out), Day 8 (End of Study/Early Termination Visit) until resolution.

Vital Signs: Blood pressure and heart rate is assessed using a sphygmomanometer and temperature by thermometer. Assessed at Screening, Day -1 (Check-in), Day 1 pre-dose, 0.5hrs, 2hrs, 6hrs & 12hrs post-dose, Day 2 24hrs post-dose, Day 3 48hrs post-dose, Day 4 72hrs post-dose, (Check-out) & Day 8 168hrs post-dose (End of Study/Early Termination Visit).

12-Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day -1 (Check-in), Day 1 pre-dose, 0.5hrs, 2hrs, 6hrs, 12hrs post-dose, Day 2 24hrs post-dose, Day 3 48hrs post-dose, Day 4 72hrs post-dose, (Check-out) & Day 8 168hrs post-dose (End of Study/Early Termination Visit).

Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and Urine samples collected at Screening, Day -1 (Check-in), Day 2 24hrs post-dose, and Day 4 72hrs post-dose, (Check-out).
Primary outcome [2] 332476 0
To assess the safety and tolerability of 15-day repeat oral doses of MVD1 in healthy volunteers.

Safety endpoints as change from baseline and where appropriate overtime and versus placebo include:
• Incidence, severity, and relationship of adverse events (AEs)/serious AEs (SAEs) (including withdrawals due to AEs)
• Change in vital signs
• Change in electrocardiogram (ECG) parameters
• Change in clinical laboratory parameters (haematology, serum chemistry, coagulation, and urinalysis)
Timepoint [2] 332476 0
Adverse Events: Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) Version 5). AEs will be assessed continuously as they are reported or observed and reviewed daily on Day -1 (Check-in), Day 1 through to Day 18 (Check-out), Day 22 (End of Study/Early Termination Visit) until resolution.

Vital Signs: Blood pressure and heart rate is assessed using a sphygmomanometer and temperature by thermometer. Assessed at Screening, Day -1 (Check-in), Day 1 pre-dose, Day 2 4hrs post-dose, Day 4 4hrs post-dose, Day 7 4hrs post-dose, Day 10 4hrs post-dose, Day 15 pre-dose, 0.5hrs, 3hrs, 6hrs post-dose, Day 16 24hrs post last-dose, Day 17 48hrs post last-dose, Day 18 (Check-out) 72hrs post last-dose and Day 22 168hrs post last-dose (End of Study/Early Termination Visit).

12-Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day -1 (Check-in), Day 1 pre-dose, 4hrs post-dose, pre-dose Day 2 4hrs post-dose, pre-dose Day 4 4hrs post-dose, pre-dose Day 7 4hrs post-dose, pre-dose Day 10 4hrs post-dose, pre-dose Day 15 6hrs post-dose, and Day 22 168hrs post last-dose (End of Study/Early Termination Visit).

Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and Urine samples collected at Screening, Day -1 (Check-in), Day 3 post Day 2 dose, Day 5 post Day 4 dose, Day 6 pre Day 7 dose, Day 8 post Day 7 dose, Day 9 pre Day 10 dose, Day 11, Day 12, Day 13, Day 14 pre Day 15 dose, Day 16 24hrs post-dose, Day 18 (Check-out) 72hrs post-dose.
Secondary outcome [1] 413679 0
To assess the pharmacokinetics (PK) of MVD1 and metabolites in plasma and urine following administration of single oral doses in healthy volunteers.

PK parameters to be calculated include (but are not limited to):
• Maximum observed plasma concentration (Cmax)
• Time to Cmax (Tmax)
• Area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC0-t)
• Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)
• Apparent terminal elimination half-life (t1/2)
• Terminal elimination rate constant (lambda z)
• Apparent clearance (CL/F).
• Apparent volume of distribution (Vz/F)
Timepoint [1] 413679 0
Plasma samples will be collected as follows:
Day 1 pre-dose within 15 mins dosing, 0.25hrs, 0.5hrs, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 10hrs 12 hrs post-dose, Day 2 24hrs post-dose, Day 3 48hrs post-dose, Day 4 (Check-out), 72hrs post-dose.

Pooled Urine samples will be collected as follows:
Overnight (from 10 pm) on Day -1 (Check-in) to pre-dose on Day 1, for up to 24 hours Day 1 post-dose, Day 2 24hrs post-dose.
Secondary outcome [2] 413680 0
To assess the pharmacokinetics (PK) of MVD1 and metabolites in plasma and urine following administration of 15-day repeat oral doses in healthy volunteers.

PK parameters to be calculated include (but are not limited to):
• Maximum observed plasma concentration (Cmax)
• Time to Cmax (Tmax)
• Area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC0-t)
• Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)
• Apparent terminal elimination half-life (t1/2)
• Terminal elimination rate constant (lambda z)
• Apparent clearance (CL/F).
• Apparent steady state volume of distribution (Vss/F) following multiple oral administration
• Accumulation ratio of AUCtau
• Accumulation ratio of Cmax
• Trough concentrations
• Minimum observed concentration Cmin (Day 15)
• Area under the plasma concentration-time curve from time 0 to tau (AUCtau)

Timepoint [2] 413680 0
Plasma samples will be collected as follows: Day 1 pre-dose 1, within 15 mins dosing, 0.25 hrs, 0.5hrs, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 10hrs, post-dose 1 and pre-dose 2 within 15 mins dosing, 0.25 hrs, 0.5hrs, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 10hrs post-dose 2. Day 2 pre-dose, within 15 mins dosing, Day 4 pre-dose, within 15 mins dosing, Day 7 pre-dose, within 15 mins dosing, Day 10 pre-dose, within 15 mins dosing, Day 15 pre-dose, within 15 mins dosing, 0.25 hrs, 0.5hrs, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 10hrs, 12hrs post-dose, Day 16 24hrs post-dose, Day 17 48hrs post-dose, Day 18 (Check-out) 72hrs post-dose. Pooled Urine samples will be collected as follows: Overnight (from 10 pm) on Day -1 (Check-in) to pre-dose on Day 1, for up to 24 hours Day 15 post-dose, Day 16 24hrs post dose
Secondary outcome [3] 413681 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Glucose
Timepoint [3] 413681 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [4] 416387 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Oral glucose tolerance test (OGTT)
Timepoint [4] 416387 0
Pharmacodynamic assessments will occur: Day -1 pre-glucose drink, 1hr, 2hrs post-glucose drink. Day 16 pre-glucose drink, 1hr, 2hrs post-glucose drink.
Secondary outcome [5] 416388 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Insulin
Timepoint [5] 416388 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [6] 416389 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• C peptide
Timepoint [6] 416389 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [7] 416390 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Glycoalbumin
Timepoint [7] 416390 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [8] 416391 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Glycohemoglobin
Timepoint [8] 416391 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [9] 416392 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Free fatty acids
Timepoint [9] 416392 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [10] 416393 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Triglycerides
Timepoint [10] 416393 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [11] 416394 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1.

Change from baseline in the following serum biomarkers:
• Leptin levels
Timepoint [11] 416394 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [12] 416395 0
To evaluate pharmacodynamic (PD) biomarker changes following multiple oral doses of MVD1. Change from baseline in the following serum biomarkers:• High sensitivity C reactive protein (hsCRP)
Timepoint [12] 416395 0
Pharmacodynamic assessments will occur:
Day 1 pre-dose, within 2-3 hrs dosing, Day 7 2hrs post-dose, Day 15 2hrs post-dose, Day 16 24hrs post-dose
Secondary outcome [13] 429106 0
To investigate MVD1 exposure in white adipose tissue
Timepoint [13] 429106 0
MVD1 exposure in white adipose tissue will be assessed using a single needle biopsy on Day 7 approximately 2 hrs (+/- 1 hr) post-dose 1.
Secondary outcome [14] 429107 0
To evaluate the participant's impression of change following multiple oral doses of MVD-1.
Timepoint [14] 429107 0
Patient general impression of change (PGIC) questionnaire to be evaluated at the end of the dosing period, Day 16.

Eligibility
Key inclusion criteria
Inclusion Criteria Cohorts S1 to S3:
1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Male or female, 18-60 years of age inclusive at the time of screening.
3. Body mass index (BMI) = 20 and < 30 kg/m2 at the time of screening.
4. Female participants:
a. Must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy or bilateral tube ligation/occlusion at least 6 weeks before the Screening visit) or postmenopausal where menopause is defined as 12 months of amenorrhea without an alternative medical cause (females must have a documented serum follicle stimulating hormone level consistent with postmenopausal status, per local laboratory guidelines) OR
b. If of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal), must agree not to attempt to become pregnant, must not donate ova and must agree to use an acceptable form of contraception from signing the consent form until at least 30 days after the last dose of study drug.
5. Male participants:
a. Must be biologically or surgically sterile (i.e, have had a vasectomy at least 3 months prior to screening) OR
b. If not biologically or surgically sterile, must agree not to donate sperm and must agree to use an acceptable contraceptive method in addition to having the female partner use an acceptable contraceptive method from signing the consent form until at least 90 days after the last dose of study drug.
6. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.

Inclusion Criteria Cohorts M1 to M3:
1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Male or female, 25-60 years of age inclusive at the time of screening.
3. In good health as determined by the outcome of medical history, physical examination, and clinical judgement by the Investigator. Chronic stable non-inflammatory conditions such as abnormal fasting glycemia, hypertension, hyperlipidemia, osteoarthritis, gout, Chronic Pain Disorders, Thyroid Disease, controlled psychiatric conditions such as anxiety or depression, are permitted, as determined by the Investigator.
4. Body mass index (BMI) between 28 and 35 kg/m2 inclusive at the time of screening.
5. Female participants:
a. Must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy or bilateral tube ligation/occlusion at least 6 weeks before the Screening visit) or postmenopausal where menopause is defined as 12 months of amenorrhea without an alternative medical cause (females must have a documented serum follicle stimulating hormone level consistent with postmenopausal status, per local laboratory guidelines) OR
b. If of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal), must agree not to attempt to become pregnant, must not donate ova and must agree to use an acceptable form of contraception from signing the consent form until at least 30 days after the last dose of study drug.
6. Male participants:
a. Must be biologically or surgically sterile (i.e, have had a vasectomy at least 3 months prior to screening) OR
b. If not biologically or surgically sterile, must agree not to donate sperm and must agree to use an acceptable contraceptive method in addition to having the female partner use an acceptable contraceptive method from signing the consent form until at least 90 days after the last dose of study drug.
7. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria Cohorts S1 to S3:
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant
2. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications
3. Any history of malignant disease in the last 10 years (excludes surgically resected skin and in situ cervical squamous cell or basal cell carcinoma)
4. Screening 12-lead ECG outside the normal range for the triplicate mean (QT interval corrected using the Fridericia method (QTcF) males > 450 msec; females > 470 msec) or with abnormalities, which are hazardous to the participant according to the opinion of the Investigator
5. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia
6. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration
7. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrhythmia
8. Change in body weight of = 5 % within 6 months prior to screening visit
9. Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total or unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT).
10. Positive test results for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit
11. Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
12. Estimated glomerular filtration rate (eGFR) < 60 mL/min /1.73 m2 or serum creatinine more than 1.5-fold above the ULN
13. History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) within 12 weeks prior to the screening visit
14. Positive urine cotinine, drugs of abuse or alcohol breath test results at the screening visit or at check-in (Day -1).
15. Use of any prescription or over-the-counter medication (including herbal products, diet aids, hormone supplements, topical ointments, vitamins and dietary supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, with the exception of hormonal contraceptives, medications used to manage AEs including the occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days).
16. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial
17. Known hypersensitivity to any of the study drug ingredients
18. Use of any vaccinations within 14 days prior to the first study drug administration
19. For women of childbearing potential, a positive serum pregnancy test at the screening visit or a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1)
20. Females who are lactating at any time during the study
21. Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to first study drug administration, or receipt of a blood transfusion within 1 year of first study drug administration
22. Participation in another clinical trial of an investigational drug within 60 days or 5 half-lives of the investigational agent (whichever is longer) prior to the first study drug administration
23. Difficulty in swallowing the study medication
24. Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements

Exclusion Criteria Cohorts M1 to M3:
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, other than those listed in the inclusion criteria above including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant.
2. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications
3. Any history of malignant disease in the last 10 years (excludes surgically resected skin and in situ cervical squamous cell or basal cell carcinoma)
4. Screening 12-lead ECG outside the normal range for the triplicate mean (QTcF males > 450 msec; females > 470 msec) or with abnormalities, which are hazardous to the participant according to the opinion of the Investigator
5. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia
6. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration
7. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrhythmia
8. Change in body weight of = 5 % within 6 months prior to screening visit
9. Liver function test results elevated more than 1.5-fold above the ULN for GGT, bilirubin (total or unconjugated), ALP, AST or ALT
10. Positive test results for active HIV, HBsAg or HCV antibodies at the screening visit
11. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
12. Estimated glomerular filtration rate (eGFR) < 60 mL/min /1.73 m2 or serum creatinine more than 1.5-fold above the ULN
13. History of substance abuse or alcohol abuse (defined as regularly consume more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) within 12 weeks prior to the screening visit
14. Positive urine cotinine, drugs of abuse or alcohol breath test results at the screening visit or at check-in (Day -1).
15. Use of any prescription or over-the-counter medication (including herbal products, diet aids, hormone supplements, topical ointments, vitamins and dietary supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, with the exception of hormonal contraceptives, medications used to manage AEs including the occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days), stable use (4 weeks or longer prior to screening) of medications used to treat hypertension and high cholesterol and medications for hay fever.
16. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial
17. Known hypersensitivity to any of the study drug ingredients.
18. Use of any vaccinations within 14 days prior to the first study drug administration
19. For women of childbearing potential, a positive serum pregnancy test at the screening visit or a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1)
20. Females who are lactating at any time during the study
21. Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to first study drug administration, or receipt of a blood transfusion within 1 year of first study drug administration
22. Participation in another clinical trial of an investigational drug within 60 days or 5 half-lives of the investigational agent (whichever is longer) prior to the first study drug administration
23. Difficulty in swallowing the study medication
24. Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements
25. A screening urinalysis result, or first morning urine protein dipstick result on Day 1 prior to first dose of study drug showing more than a trace of protein. Test may be repeated to confirm.
26. Body weight > 120 kg at screening

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)
Randomisation numbers assigned will be in accordance with the randomisation schedule. The randomisation schedules will be maintained under controlled access. As the study is double-blinded, sealed participant-specific code break envelopes will be produced by the unblinded statistician(s) and will be retained at the clinical facility in a secure, accessible location. The assigned study personnel responsible for the dispensing of the study treatments will be accountable for ensuring compliance to randomisation schedules.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
All study participants who sign an informed consent form at screening will receive a unique sequential number (i.e., a Screening Number). Participants who meet the study eligibility criteria will be assigned a randomisation number on Day 1, which corresponds to a study treatment (MVD1 or placebo). The allocation to MVD1 or placebo will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This study is a First in Human (FIH) study with MVD1 and as such no formal sample size calculation was performed. The chosen sample size chosen is deemed adequate to evaluate all study endpoints.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/03/2023
Actual
10/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
42
Accrual to date
17
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 23127 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 38486 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 312193 0
Commercial sector/Industry
Name [1] 312193 0
Eolo Pharma Pty Ltd
Country [1] 312193 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Eolo Pharma Pty Ltd
Address
Level 5, 63 Pirie Street, Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 313723 0
Commercial sector/Industry
Name [1] 313723 0
Avance Clinical Pty Ltd
Address [1] 313723 0
13 Glynburn Road, Firle, South Australia 5070
Country [1] 313723 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311580 0
Bellberry Limited HREC
Ethics committee address [1] 311580 0
123 Glen Osmond Road, Eastwood, SA, 5063
Ethics committee country [1] 311580 0
Australia
Date submitted for ethics approval [1] 311580 0
09/11/2022
Approval date [1] 311580 0
20/12/2022
Ethics approval number [1] 311580 0
2022-11-1179

Summary
Brief summary
This is a two-part, double-blind, placebo-controlled, Phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of MVD1 in healthy volunteers. The decision to escalate between dose levels and proceed from Part A to Part B will be based on review of the safety and available PK data by the study safety review committee (SRC) from a minimum of 5 active treated participants per cohort. The SRC may recommend repeat of a cohort, or a change in the dose levels of subsequent cohorts, or that no further dose escalation cohorts occur and recommend the final sample size of the MAD cohorts based upon consensus and emerging data from safety, PK and PD biomarkers.

In Part A, screening for study eligibility will occur between Day -28 and Day -2 inclusive. Following confirmation of eligibility on Day -1, participants will be randomised to be enrolled in Cohorts S1, S2 or S3 and to receive either MVD1 or placebo. Participants will then be admitted to the clinical facility. The confinement period will commence on Day -1, followed by dosing on Day 1 with placebo or active drug in a double-blind manner. Participants will receive a single oral dose of MVD1 or placebo on Day 1. Participants will be discharged from the clinical facility on Day 4 following completion of study assessments and will be required to attend the clinic for a final follow-up visit on Day 8 ± 1 Day.

In Part B, screening for study eligibility will occur between Day -35 and Day -2 inclusive. Following confirmation of eligibility on Day -1, participants will be randomised to be enrolled in Cohorts M1, M2, or M3 and to receive either MVD1 or placebo. Participants will then be admitted to the clinical facility. In Part B, the confinement period will commence on Day -1, followed by dosing on Day 1 with placebo or active drug in a double-blind manner. Participants will receive twice daily oral doses of MVD1 or placebo (administered 12 hours apart) on Days 1-14 and a single dose on the morning of Day 15 (total of 29 doses). Participants will be discharged from the clinical facility on Day 18 following completion of study assessments and will be required to attend the clinic for a final follow-up visit on Day 22 ± 1 Day.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121598 0
Prof Sepehr Shakib
Address 121598 0
CMAX Clinical Research,
Level 6, 21 North Terrace,
Level 5 and 6 18a North Terrace,
Adelaide SA 5000, Australia
Country 121598 0
Australia
Phone 121598 0
+61 411 100 278
Fax 121598 0
Email 121598 0
sepehr.shakib@cmax.com.au
Contact person for public queries
Name 121599 0
Prof Sepehr Shakib
Address 121599 0
CMAX Clinical Research,
Level 6, 21 North Terrace,
Level 5 and 6 18a North Terrace,
Adelaide SA 5000, Australia
Country 121599 0
Australia
Phone 121599 0
+61 411 100 278
Fax 121599 0
Email 121599 0
sepehr.shakib@cmax.com.au
Contact person for scientific queries
Name 121600 0
Prof Sepehr Shakib
Address 121600 0
CMAX Clinical Research,
Level 6, 21 North Terrace,
Level 5 and 6 18a North Terrace,
Adelaide SA 5000, Australia
Country 121600 0
Australia
Phone 121600 0
+61 411 100 278
Fax 121600 0
Email 121600 0
sepehr.shakib@cmax.com.au

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


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
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