Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000137594
Ethics application status
Approved
Date submitted
12/12/2023
Date registered
14/02/2024
Date last updated
14/02/2024
Date data sharing statement initially provided
14/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 1, Randomised, placebo-controlled, single-blind, single-ascending dose study, to determine the safety and tolerability of intravenous Gemini in healthy volunteers.
Scientific title
A phase 1, Randomised, placebo-controlled, single-blind, single-ascending dose study, to determine the safety and tolerability of intravenous Gemini in healthy volunteers.
Secondary ID [1] 310928 0
RVL-HV02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-surgical infection 331993 0
Condition category
Condition code
Surgery 328733 328733 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will enrol up to 40 participants in up to 5 cohorts, the 5th Cohort (Cohort 4b) will be a repeat dose of Cohort 4a. The dose administered in each cohort will be:
Cohort 1 - 30ug
Cohort 2 - 90ug
Cohort 3 - 270ug
Cohort 4a - 540ug
Cohort 4b - 540ug or maximum tolerated dose (MTD)

Each cohort will consist of 8 unique participants (6 assigned to Gemini), sentinel dosing will be conducted in cohorts 1, 2, 3 and 4a. Sentinal dosing will not be required for Cohort 4b since the dose is a repeat of Cohort 4 a. Additional participants (up to 8) may be necessary if a dose limiting toxicity (DLT) occurs.

All participants will be screened for eligibility before enrolment. Screened participants who provide written informed consent and meet all eligibility criteria will be admitted to the clinical research unit (CRU) on Day -1.

On Day 1, each study participant will receive a single intravenous dose via syringe pump for at least 10 minutes but not longer than 15 minutes.

Two participants in each cohort, each participant will receive a single intravenous (sentinel) dose. If either participant experiences a dose DLT, or meets the criteria for stopping doses prior to Day 2/Hour 24, the cohort will be stopped. Sentinel dosing will not be required for Cohort 4b since the dose is a repeat of Cohort 4a.

Participants will be confined on Day -1 and discharged on Day 2 after all study procedures are complete. All other visits will be conducted as an outpatient or via telephone.

The study drug will be administered to eligible participants under the supervision of the PI or identified Sub-I(s). The pharmacist or designee will maintain records of investigational product receipt, preparation, and dispensing, including the applicable lot numbers, and total drug administered. Any discrepancy between the assigned dose and dose administered, as well as the reason for the discrepancy, are to be recorded in the source documents and the eCRF.
Intervention code [1] 327361 0
Treatment: Drugs
Comparator / control treatment
Matched placebo will be composed of 5% sugar solution for intravenous administration.
Control group
Placebo

Outcomes
Primary outcome [1] 336582 0
To evaluate the safety and tolerability of Gemini after single ascending IV doses. These will be assessed as a composite primary outcome.
Timepoint [1] 336582 0
Adverse events: Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). AEs will be assessed continuously as they are reported or observed and reviewed on Day-1, Day 1 Pre-dose, Day 1 Post-dose (at 1min, 20min, 2hrs, 4 hrs, and 12hrs), Day 2 Post-dose (24hrs), Day 3 (48hrs), Day 4 (72hrs), Day 5 (96hrs), Day 6 (120hrs), Day7 (144hrs) and Day 8 (168hrs)/End of study.

Vital signs: Vital signs including blood pressure, heart rate, respiratory rate will be assessed using a sphygmomanometer, and body temperature by thermometer after the participant has been resting in a supine, semi-supine or sitting position for at least 5 minutes. Assessed at Screening, Day -1, Day 1 Pre-dose, Day 1 Post-dose (20min, 2hrs, 4hrs, 12hrs), Day 2 (24hrs), Day 3 (48hrs) Day 6 (120hrs) and Day 8 (168hrs)/End of Study.

Electrocardiogram (ECG): ECG recordings will be performed in triplicate at screening only with each replicate separated by at least 1 minute and the full set of triplicates completed within 5 minutes. Assessed at Screening, Day 1 Pre-dose, Day 1 Pose-dose (2hrs), Day 3 (48hrs) and Day 8 (168hrs)/End of Study

Clinical laboratory evaluations: including haematology, chemistry, serology and urinalysis, Blood collected at Screening, Day -1, Day 1 Post-dose (2hr, 4hrs, 12hrs), Day 2 (24hrs), Day 3 (48hrs), Day 6 (120hrs), Day 8 (168hrs)/End of Study. Urine collected at Screening and Day 8 (168hrs)/End of Study.
Secondary outcome [1] 428871 0
To assess the pharmacokinetics (PK) of Gemini after single ascending IV doses.
Timepoint [1] 428871 0
Blood samples will be collected as follows:
Day 1 Pre-dose
Day 1 Post-dose (1min, 20min, 2hr, 4hr, 12hr).
Day 2 Post-dose (24hrs, 48hrs)
Secondary outcome [2] 428872 0
Exploratory Objective: To measure the effect of Gemini on pharmacodynamic activity and evaluate changes in potential pharmacodynamic (PD) markers.
Timepoint [2] 428872 0
Blood samples will be collected as follows:
Day 1 Pre-dose
Day 1 Post-dose (20min. 2hrs, 4hrs, 12hrs)
Day 2 Post-dose 24hrs
Day 3 Post-dose 48hrs
Day 6 Post-dose 120hrs
Day 8 post-dose 168hrs/End of Study

Eligibility
Key inclusion criteria
Healthy volunteers will be included in the study if they satisfy all the following criteria:
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. Adult volunteers, 18 to 55 years of age, inclusive, at Screening.
3. Is medically healthy (in the opinion of the PI or identified Sub-I(s)), as determined by pre-study medical history, and without clinically significant abnormalities including:
• Physical examination without any clinically relevant findings
• Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in a sitting, supine or semi-supine position
• Heart rate (HR) in the range of 45 to 100 bpm after 5 minutes rest in a sitting, supine or semi-supine position
• Body temperature (tympanic), between 35.5°C and 37.7°C
• Electrocardiogram (ECG) without clinically significant abnormalities including QT interval corrected for Fredericia (QTcF) <450 msec for male subjects and <470 msec for female subjects
• No clinically significant findings in serum chemistry, haematology and urinalysis tests
4. Non-smoker, non-tobacco user and non-nicotine product user or a former smoker/user (has not smoked, vaped or used tobacco/nicotine products in the 6 months prior to dosing.
5. Participant must have a Body Mass Index (BMI) greater than or equal to 18.0 kg/m2 and less than or equal to 32.0 kg/m2 at screening.
6. Female participants must be of non-childbearing potential or using a medically acceptable contraceptive regimen from screening until 30 days post dose.
7. Male participants must be surgically sterile or using a medically acceptable contraceptive regimen from screening until 90 days post dose.
8. Participant must be willing and able to comply with the study schedule, restrictions, and requirements.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Volunteers will be excluded from the study if there is evidence of any of the following:
1. Known hypersensitivity to any of the study drug ingredients.
2. Concomitant disease, disability, or condition which may interfere with the conduct of the study, or which would, in the opinion of the PI or identified Sub-I(s), pose an unacceptable risk to the participants in this study, including, but not limited to alcohol dependency or abuse (in the past 2 years defined as >21 units of alcohol per week for males and >14 units of alcohol per week for females. Where 1 unit = 360mL of beer, 150mL of wine, or 45mL of spirits), drug dependency or abuse (in the past 2 years), or previously diagnosed psychiatric disease (stable depression is acceptable).
3. Positive drugs of abuse test, cotinine test or alcohol breath test results at the screening and/or Day -1.
4. Do not have suitable veins for multiple venipunctures/cannulations as assessed by the PI or identified Sub-I(s) at screening.
5. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <80 mL/min using the Cockcroft-Gault equation at screening and Day -1.
6. Abnormal liver function tests as indicated by alanine aminotransferase (ALT) > 1.5x upper limit of normal (ULN), aspartate aminotransferase (AST) > 1.5 x ULN or total bilirubin >1.5 x ULN at screening and Day -1.
7. Verbal history of risk factors or symptoms for SARS-CoV-2 at Screening and Day -1.
8. Have hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV-1 or HIV-2) at screening.
9. Verbal history of being immunocompromised due to disease or medication (e.g., cancer immunosuppressive therapy), hypertension, coronary artery disease with history of stent or graft, heart failure NYHA class 2 or greater, or diabetes at screening.
10. Used any prescription medications within 14 days, or over-the-counter medications within 7 days of Day -1, with the exception of contraceptives or hormone replacement therapy for female participants and occasional paracetamol use (at the discretion of the PI or identified Sub-I(s)).
11. Used vitamins, dietary or herbal supplement, or nutritional supplement within 7 days of Day -1.
12. Administration of systemic antibiotics or antivirals within 7 days of Day -1 (excluding topical/external use of antibiotics).
13. History of surgery or hospitalization within 3 months of Day -1, or surgery planned during the study.
14. Pregnant or breast-feeding women.
15. Participant has received any immunoglobulins and/or blood products within 3 months of Day -1.
16. Participant has donated blood or plasma within 30 days prior to screening or had a loss of whole blood of more than 500ml within the 30 days prior to screening.
17. Participant has had acute respiratory illness within 30 days of Day -1.
18. Participant has received treatment with any investigational product in any clinical study within 30 days of Day -1 or five half-lives, whichever is longer.
19. Participant has received a vaccination within 30 days of Day -1.
20. Participant is unwilling or unable to comply with the study protocol requirements.

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)
Following confirmation of study eligibility, participants will be assigned a unique participant enrolment number and assigned to a treatment cohort.
The study pharmacist, or designee at the clinical research unit, will assign 1 participant to placebo and 1 participant to Gemini at the start of each cohort based on a computer-generated randomisation list.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a computer-generated randomisation list.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data will be summarised using descriptive statistics (number of observations, mean, median, standard deviation [SD], minimum and maximum) or frequency counts and percentages, as appropriate to the type of data
Demographics, baseline characteristics, medical history, disposition, and concomitant medication data will be presented by treatment group and for all participants overall. All other results will be presented by treatment group (Gemini or placebo).
Unless specifically stated otherwise, two-sided 95% confidence intervals (CIs) will be displayed where appropriate. All inferential analyses will be performed using two-sided tests at a 5% level of significance.
All data will be included in the data listings.
For the safety analyses, the period baseline value will be defined as the last available non-missing pre-dose measurement within each of the periods. The overall baseline will be defined as the last available non-missing pre-dose measurement before study drug administration.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/03/2024
Actual
Date of last participant enrolment
Anticipated
11/06/2024
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 25839 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 41667 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 315188 0
Commercial sector/Industry
Name [1] 315188 0
Revelation Biosciences Sub Inc
Country [1] 315188 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Revelation Biosciences Sub Inc
Address
4660 La Jolla Village Drive, Suite 100, San Diego CA 92122
Country
United States of America
Secondary sponsor category [1] 317214 0
None
Name [1] 317214 0
Address [1] 317214 0
Country [1] 317214 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314119 0
Bellberry Limited Human Research Ethics Committee
Ethics committee address [1] 314119 0
123 Glen Osmond Road, Eastwood, SA, 5063
Ethics committee country [1] 314119 0
Australia
Date submitted for ethics approval [1] 314119 0
15/11/2023
Approval date [1] 314119 0
13/02/2024
Ethics approval number [1] 314119 0

Summary
Brief summary
Gemini is being developed as a potential new drug as a treatment for reducing the incidence, duration, and severity of acute kidney injury following cardiac surgery and for surgical site infection. The purpose of this research study is to evaluate safety, tolerability, how the body uses the drug and how the drug affects the body in healthy participants.
The study drug works by stimulating a protein called toll-like receptor, which plays an important role in activating the natural immune response. The immune system is the body's first line of defence against invaders such as viruses, bacteria, parasites or toxins entering the body, or to detect wounds in trauma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130474 0
Dr Jasmine Williams
Address 130474 0
Linear Clinical Research, 1 Hospital Avenue, B-Block, 1st Floor, Nedlands, WA 6009
Country 130474 0
Australia
Phone 130474 0
+61 0 439694508
Fax 130474 0
Email 130474 0
jwilliams@linear.org.au
Contact person for public queries
Name 130475 0
Dr Jasmine Williams
Address 130475 0
Linear Clinical Research, 1 Hospital Avenue, B-Block, 1st Floor, Nedlands, WA 6009
Country 130475 0
Australia
Phone 130475 0
+61 0 439694508
Fax 130475 0
Email 130475 0
jwilliams@linear.org.au
Contact person for scientific queries
Name 130476 0
Dr Jasmine Williams
Address 130476 0
Linear Clinical Research, 1 Hospital Avenue, B-Block, 1st Floor, Nedlands, WA 6009
Country 130476 0
Australia
Phone 130476 0
+61 0 439694508
Fax 130476 0
Email 130476 0
jwilliams@linear.org.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
No additional documents have been identified.