Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001209785
Ethics application status
Approved
Date submitted
25/08/2022
Date registered
8/09/2022
Date last updated
13/01/2023
Date data sharing statement initially provided
8/09/2022
Date results information initially provided
13/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to investigate ARG-007 in Healthy Volunteers
Scientific title
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Sequential-Group Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of ARG-007 in Healthy Participants
Secondary ID [1] 307825 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 327428 0
Condition category
Condition code
Stroke 324553 324553 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patient outcomes following an ischaemic stroke are significantly improved by rescuing the ischaemic penumbra, the severely hypoperfused and hypoxic, electrically silent, at-risk brain tissue. ARG-007 offers the potential to reduce neuronal cell death and preserve still viable tissue in the penumbra in patients by disrupting the excitotoxic pathway that a stroke initiates, resulting in potentially enhanced functional recovery.
This is a double-blind, randomized, placebo-controlled, study to assess the safety, tolerability, and pharmacokinetics of single ascending doses of ARG-007 in healthy participants at a single site in Australia.
At least 32 participants will receive either study drug or matched placebo at one of four dose levels (0.03 mg/kg, 0.10 mg/kg, 0.20 mg/kg, 0.30 mg/kg) via slow intravenous infusion over ten minutes. Participants will stay to complete safety assessments up to 48 hours post dose, and then return to the clinical site on Day 8 (± 1 day) for follow up assessments.
Trained nurses will be administering the study drugs to the participants.
Intervention code [1] 324291 0
Treatment: Drugs
Comparator / control treatment
The placebo is commercially available 0.9% Saline and identical in appearance to ARG-007.
Control group
Placebo

Outcomes
Primary outcome [1] 332386 0
The objective of this study is to evaluate the safety and tolerability of single escalating doses of ARG-007. Safety assessments include the monitoring of incidence and severity of adverse events. These will be reported by the participant to study site staff. Open-ended and non-leading verbal questioning of the participant will be used to inquire about AE occurrences.
As this is a first in human trial of ARG-007, therefore there are no examples of known adverse events in humans.
Clinically significant changes from baseline will also be monitored in:
- laboratory evaluations (hematology, chemistry, urinalysis)
- electrocardiograms (ECG) ; using a 12 lead ECG machine.
- vital signs including oral or tympanic temperature, pulse rate, respiratory rate and blood pressure. Temperature, blood pressure and pulse rate are assessed using a vitals machine.
Respiratory rate is assessed using a 30 second manual count.
- physical examinations including examination of the following general appearance, head, ears, eyes, nose, throat, neck (including thyroid), skin, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes and nervous system. This will be performed by a study delegated registered physician.
Timepoint [1] 332386 0
Dosing will occur on Day 1..
Adverse events will be monitored throughout the study, This will be Day 1 to Day 3 inclusive and at a End of Study visit on Day 8.
Laboratory evaluations will occur at participant check in (Day -1) and at Day 2 and 3 and at End of Study visit on Day 8.
ECG will be performed at check in, Day 1-3 inclusive and at End of Study visit on Day 8.
Vital signs will be monitored at check in, Day 1-3 inclusive and at End of Study visit on Day 8.
Physical exam will be performed at check in, Day 1, 3 and at End of Study visit on Day 8.
Secondary outcome [1] 413295 0
To determine the pharmacokinetic profile of ARG-007 following single dose administration. Pharmacokinetic parameters of ARG-007 in plasma include the area under the plasma concentration curve, peak plasma concentration, time to peak plasma concentration, clearance, volume of distribution and elimination half-life.
Timepoint [1] 413295 0
PK blood samples will be collected from subjects pre-dose, at dose and then post dose at 5 min, 10 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 48 hours,
Secondary outcome [2] 413319 0
To assess the immune response to ARG-007 following single dose administration by looking at changes from baseline in levels of multiple cytokines (tumor necrosis factor alpha, interferon gamma and interleukin (IL)-2, IL-4, IL-6, IL-8, and IL-10).
Timepoint [2] 413319 0
Cytokine blood samples will be collected from subjects pre-dose and then post-dose at 15 min, 2 hours, 24 hours, 48 hours, 168 hours.

Eligibility
Key inclusion criteria
1. Any gender, aged 18 to 65 inclusive at the time of screening;
2. Generally healthy with the exception of those medical conditions allowed as per the inclusion/exclusion criteria;
3. Body mass index 18.0 to 32.0 kg/m2, inclusive at the time of screening and Day -1;
4. Weight between 50.0 to 100.0 kg at the time of screening and at Day -1;
5. Provision of voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures;
6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1 and must not be breastfeeding, lactating or planning pregnancy during the study period. WOCBP must agree to use an acceptable form of contraception during the treatment period and for at least 28 days post dose.
7. 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 90 days post dose and refrain from donating sperm for at least 90 days post-dose.
8. Subjects must have the ability and willingness to attend the necessary visits to the study center.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Have any underlying physical or psychological medical condition that, in the opinion of the investigator, would make it unlikely that the subject will complete the study;
2. Any significant past or current cardiac, pulmonary, hepatic, renal or other medical condition which, in the opinion of the investigator, would make participation in this study medically unsafe or compromise the study endpoints;
3. History of significant hypersensitivity such as urticaria, angioedema, or anaphylaxis;
4. Subjects with past medical history of malignancy except basal cell or squamous cell carcinoma of the skin who have had curative surgical treatment and at least 6 months have elapsed since the procedure;
5. Clinically significant laboratory abnormality (as judged by the investigator) at any time prior to dosing. Can be repeated once during screening at the discretion of the investigator;
6. Systolic blood pressure outside 100 to 140 mmHg or diastolic blood pressure outside of 50 to 90 mmHg at any point prior to dosing. Can be repeated at two different timepoints at the discretion of the investigator;
7. Clinically significant ECG abnormality (as judged by the investigator) at any time prior to dosing;
8. Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibodies at screening;
9. Use of angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) to control blood pressure;
10. Use of prescription medicines, over-the-counter medicines, vitamins or supplements within 7 days, or 5 half-lives (whichever is longer) prior to dosing until the EOS visit. The use of hormone replacement therapy, hormonal contraception or paracetamol (less than or equal to 2 g per day) is permitted;
11. Use of alcohol, nicotine and tobacco-containing products, and recreational vaping products from 48 hours prior to Day -1;
12. Unwilling to avoid heavy exercise (eg, marathon runners, weight-lifters) for five days prior to Day -1 until the EOS visit;
13. Alcohol or recreational substance use in the 12 months prior to dosing which has caused medical, psychological or other consequences, or which is considered to possibly impact participant safety or data validity;
14. Positive urine drug screen at screening or Day -1;
15. Blood donation or significant blood loss within 60 days prior to Day -1;
16. Plasma donation within 14 days prior to Day -1;
17. Administration of an investigational product in another study within 30 days or 5 x half-life (whichever is longer) prior to Day -1;
18. Surgery within the past 3 months prior Day -1 determined by the investigator to be clinically relevant;
19. Active infection (diagnosed or suspected) or history of recurrent infection;
20. History of clinically significant acute bacterial, viral, or fungal systemic infections in the 4 weeks prior to screening;
21. Serious local infection or systemic infection requiring antibiotic treatment within 3 months prior to screening;
22. Known alpha 1-antitrypsin deficiency (a1-antitrypsin deficiency);
23. Any vaccination within 2 weeks prior to Day -1, or requiring vaccination during the study or within 2 weeks after completion of the study;
24. Any significant acute illness within 30 days prior to Day -1.

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)
All eligible subjects will be randomised using a central randomisation by computer model.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
The sample size for this study has been selected based on practical considerations without performing a formal sample size calculation. The sample size is typical for studies of this nature and is considered adequate to assess the study objectives.

Statistical Analysis Plan:
A Statistical Analysis Plan (SAP) will be written after finalizing the protocol and prior to database lock. The SAP will detail the implementation of all the planned statistical analysis in accordance with the principal features stated in the protocol. Any deviations from the SAP will be presented in the final clinical study report.
Results will be presented by treatment group and subjects randomized to placebo will be pooled for analysis (where appropriate). In general, data will be summarized using descriptive statistics (number of subjects [n], mean, median, standard deviation [SD], minimum and maximum) or frequency counts and percentages, as appropriate to the type of data. The coefficient of variation (CV%) and geometric mean will also be presented in the PK concentrations and parameters summaries. Baseline will be defined as the last available, valid, non-missing assessment prior to dosing. Only data from protocol scheduled visits/time points will be included in the summary tables. Data from unscheduled visits/time points will not be included in the summary tables but will be included in the figures and listings.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/10/2022
Actual
19/09/2022
Date of last participant enrolment
Anticipated
Actual
2/12/2022
Date of last data collection
Anticipated
Actual
21/12/2022
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 312099 0
Commercial sector/Industry
Name [1] 312099 0
Argenica Therapeutics Ltd
Country [1] 312099 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Argenica Therapeutics Ltd.
Address
4/117 Broadway, Nedlands, 6009, WA
Country
Australia
Secondary sponsor category [1] 313618 0
None
Name [1] 313618 0
Address [1] 313618 0
Country [1] 313618 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311501 0
Bellberry Ltd.
Ethics committee address [1] 311501 0
23 Glen Osmond Rd, Eastwood, 5063, SA
Ethics committee country [1] 311501 0
Australia
Date submitted for ethics approval [1] 311501 0
10/08/2022
Approval date [1] 311501 0
06/09/2022
Ethics approval number [1] 311501 0

Summary
Brief summary
Patient outcomes following an ischaemic stroke are significantly improved by rescuing the ischaemic penumbra, the severely hypoperfused and hypoxic, electrically silent, at-risk brain tissue. ARG-007 offers the potential to reduce neuronal cell death and preserve still viable tissue in the penumbra in patients by disrupting the excitotoxic pathway that a stroke initiates, resulting in potentially enhanced functional recovery.
This is a double-blind, randomized, placebo-controlled, study to assess the safety, tolerability, and pharmacokinetics of single ascending doses of ARG-007 in healthy participants at a single site in Australia.
The primary objective of this study is to evaluate the safety and tolerability of single escalating doses of ARG-007 in healthy participants for 8 days, administered by intravenous infusion.
The secondary objectives are to determine the pharmacokinetic profile and immune response profile of ARG-007 in healthy participants following single dose administration.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121322 0
Dr Andrew Redfern
Address 121322 0
Linear Clinical Research
1 Hospital Avenue, B-Block, 1st Floor,
Nedlands WA 6009
Country 121322 0
Australia
Phone 121322 0
+61 0433 078719
Fax 121322 0
Email 121322 0
aredfern@linear.org.au
Contact person for public queries
Name 121323 0
Ms Nicola Norton
Address 121323 0
Linear Clinical Research
1 Hospital Avenue, B-Block, 1st Floor,
Nedlands WA 6009
Country 121323 0
Australia
Phone 121323 0
+61 8 6382 5100
Fax 121323 0
Email 121323 0
contactus@linear.org.au
Contact person for scientific queries
Name 121324 0
Dr Andrew Redfern
Address 121324 0
Linear Clinical Research
1 Hospital Avenue, B-Block, 1st Floor,
Nedlands WA 6009
Country 121324 0
Australia
Phone 121324 0
+61 8 6382 5100
Fax 121324 0
Email 121324 0
contactus@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
IPD will not be available


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.