Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001609145
Ethics application status
Approved
Date submitted
11/11/2019
Date registered
21/11/2019
Date last updated
17/05/2022
Date data sharing statement initially provided
21/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 study to evaluate Safety, Tolerability and Pharmacokinetics of LMR-123 in Healthy Subjects
Scientific title
A Phase 1, Randomized, Placebo-controlled Safety, Tolerability and Pharmacokinetic Study of Single Ascending Doses of LMR-123 in Healthy Subjects
Secondary ID [1] 299780 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Ischemic Stroke 315126 0
Condition category
Condition code
Stroke 313446 313446 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be administered LMR-123 or matching placebo in cohort 1-7 via intravenous infusion over 30 minutes on day 1 as below:
• Cohort 1 – 2 mg/kg LMR-123 (n=4), (open label);
• Cohort 2 – 4 mg/kg LMR-123 (n=6), placebo (n=2) (blinded);
• Cohort 3 – 8 mg/kg LMR-123 (n=6), placebo (n=2) (blinded);
• Cohort 4 – 12 mg/kg LMR-123 (n=6), placebo (n=2) (blinded);
• Cohort 5 – 16 mg/kg LMR-123 (n=6), placebo (n=2) (blinded);
• Cohort 6 – 20 mg/kg LMR-123 (n=6), placebo (n=2) (blinded);
• Cohort 7 (Subjects of East Asian & South East Asian descent only) -12mg/Kg LMR-123 (n=6), placebo (n=2) (blinded)
Intervention code [1] 316019 0
Treatment: Drugs
Comparator / control treatment
Matching placebo (vehicle lipid emulsion): 10% Soybean Oil, 1.2% Egg Yolk Lecithin, 2.25% Glycerol, appropriate amounts of Sodium Hydroxide, Hydrochloric acid and Water for Injection.
Control group
Placebo

Outcomes
Primary outcome [1] 321918 0
Evaluate the safety and tolerability of escalating doses of LMR-123 administered as an intravenous injection in healthy subjects compared to placebo.
Timepoint [1] 321918 0
Physical examinations, AEs, vital signs, ECG and clinical laboratory assessments measured throughout the study from screening to End of Study visit to assess any significant changes from baseline results.
Secondary outcome [1] 376709 0
Evaluate Pharmacokinetics of LMR-123 (Cohorts 2-7) measuring: - Area under the serum LMR-123 concentration curve to the last measurable data point; - Area under the serum LMR-123 concentration curve extrapolated to infinity; - Peak serum concentration; - Time to peak serum concentration; - Elimination half-life; - Clearance; - Volume of distribution; - Individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves; - Mean resistance time.
Timepoint [1] 376709 0
Pharmacokinetic samples are taken during the treatment period for Cohorts 2 - 7; Pre-dose (within 10 minutes), 15, 30, 35, 45 minutes, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1. 24 hours on Day 2. 48 hours on Day 3 and 72 hours Day 4.
Secondary outcome [2] 376973 0
Identify the structures of LMR-123 metabolites in plasma, urine and fecal samples (subjects in Cohort 4 only)
Timepoint [2] 376973 0
Urine samples are collected at pre-dose (within 2 hours), end of infusion (up to 4 hours), 4-8 hours post-infusion, 8-12 hours post-infusion, 12-48 hours post-infusion, 48-72 hours post-infusion.
Fecal samples are collected pre-dose (within 24 hours) and between 0-72 hours post-infusion.
Plasma samples are collected pre-dose (within 10 minutes), 15, 30, 35, 45 minutes, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1. 24 hours on Day 2. 48 hours on Day 3 and 72 hours Day 4.

Eligibility
Key inclusion criteria
1. Male or female healthy subjects, aged 18 to 49 years inclusive;
2. Body mass index of >19.0 kg/m2 to <29.0 kg/m2 at screening;
3. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
• Not of childbearing potential, defined as surgically sterile or postmenopausal.
• Of childbearing potential and agrees to use a highly effective method of contraception consistently during the treatment period and for at least 60 days after the last dose of investigational product;
4. A male subject with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during the treatment period and for at least 60 days after the last dose of investigational product All male subjects must refrain from donating sperm during the treatment period and for at least 60 days after the last dose of investigational product ;
5. Females of childbearing potential must have a negative pregnancy test at screening (serum) and Day 1 (urine)
6. The subject must voluntarily provide written informed consent prior to any study procedures being performed and is willing and able to comply with procedures required in this protocol.

Additional Inclusion Criteria for Cohort 7 Only:
7. Be of East Asian/South East Asian descent: Both parents must be from China, Hong Kong, Japan, Macau, Mongolia, North Korea, South Korea, Taiwan, Indochinese Peninsula comprising of Cambodia, Laos, Myanmar, Peninsula Malaysai, Thailand, Vietnam, Malay Archipelago/Nusantara comprising of the Andaman and Nicobar
Islands (India), Brunei, East Malaysia, East Timor, Indonesia (except Western New Guinea), Phillipines and Singapore.
Minimum age
18 Years
Maximum age
49 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or evidence of a clinically significant disorder.
2. History significant ophthalmic diseases including but not limited to vitreous opacities, glaucoma, cataract, ophthalmic infection and ophthalmic tumor;
3. History or presence of conditions known to interfere with the distribution, metabolism, or excretion of drugs;
4. Unwillingness to abstain from alcohol from 48 hours prior to investigational product administration.
5. A positive urine drug screen or alcohol breath test at screening;
6. Subjects smokes more than 10 cigarettes per day within 3 months of screening
7. History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study;
8. History of significant neurological diseases, including stroke, transient ischemic attacks, seizures, and vascular malformations;
9. Positive screen for human immunodeficiency virus, hepatitis B virus surface antigen or hepatitis C virus antibody;
10. Treatment with any investigational product within 30 days or 5 half-lives
11. Use of prescription or over the counter medications within 14 days of investigational product administration and during the study, with the exception of contraceptive medications, paracetamol and vitamins;
12. History of cancer,
13. History of allergic reactions
14. Subject has a positive test for tuberculosis (TB) during screening or a known history of active or latent TB
15. Donation or collection of more than or equal to 400 mL of blood for any other purpose within 12 weeks more than or equal to 200 mL within 4 weeks, or donation of blood by apheresis within 2 weeks of the planned first dose.
16. Subject does not agree to avoid food or beverages likely to influence liver metabolism 7 days prior to the first dose of the investigational product until the end of study visit;
17. Subject does not agree to refrain from consuming caffeinated beverages from 48 hours before check-in on Day -1 until completion of the confinement period.

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)
Cohort 1 is open label so randomization is not applicable.
For Cohort 2-7, a computer-generated randomization schedule will be prepared by an unblinded statistician prior to the start of the study. At the time of randomization, the subject will be assigned a unique randomization number, which will be allocated sequentially based on the pre-determined randomization schedule, and according to their chronological order of inclusion in the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size for this study is up to 52 subjects, this includes 1 cohort of 4 subjects, and 6 cohorts of 8 subjects. The sample size for this study has been selected without performing a formal sample size calculation.
In general, data will be summarized using descriptive statistics (mean, median, standard deviation, minimum and maximum) for the continuous variables or frequency counts and percentages for the categorical variables, as appropriate to the type of data. Baseline will be defined as the last available, valid, non-missing assessment prior to dosing.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/12/2019
Actual
21/01/2020
Date of last participant enrolment
Anticipated
27/02/2020
Actual
23/07/2021
Date of last data collection
Anticipated
6/03/2020
Actual
29/07/2021
Sample size
Target
52
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 15130 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 28424 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304232 0
Commercial sector/Industry
Name [1] 304232 0
Australia Medical Industries Pty Ltd
Country [1] 304232 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Australia Medical Industries Pty Ltd.
Address
73 Bradman Street
Greystanes, NSW 2145, Australia
Country
Australia
Secondary sponsor category [1] 304471 0
None
Name [1] 304471 0
None
Address [1] 304471 0
None
Country [1] 304471 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304693 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 304693 0
Ethics committee country [1] 304693 0
Australia
Date submitted for ethics approval [1] 304693 0
03/09/2019
Approval date [1] 304693 0
04/12/2019
Ethics approval number [1] 304693 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97890 0
Prof Guy Ludbrook
Address 97890 0
PARC Clinical Research
Royal Adelaide Hospital
Level 4G.1, East Wing,
Port Road, Adelaide
South Australia, 5000
Country 97890 0
Australia
Phone 97890 0
+61 8 7074 1258
Fax 97890 0
+61 8 7074 6146
Email 97890 0
[email protected]
Contact person for public queries
Name 97891 0
Guy Ludbrook
Address 97891 0
PARC Clinical Research
Royal Adelaide Hospital
Level 4G.1, East Wing,
Port Road, Adelaide
South Australia, 5000
Country 97891 0
Australia
Phone 97891 0
+61 8 7074 1258
Fax 97891 0
+61 8 7074 6146
Email 97891 0
[email protected]
Contact person for scientific queries
Name 97892 0
Jiaxu Wu
Address 97892 0
Australian Medical Industries
73 Bradman Street
Greystanes, NSW 2145
Country 97892 0
Australia
Phone 97892 0
+61 413 352 828
Fax 97892 0
Email 97892 0
[email protected]

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


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.