General Discussions, page-93

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385922&isReview=true&fbclid=IwAR2yCbbpq0kmlPYbWspyTVCgX8WTChPcM1oYrdiM4QIjhB6NdLuXrotT4Bk_aem_AeDIHFOOnG9AxQEAvwvNhSGQnwGLvTqS_J3xibRsd8oqp1mTwHDUWzZWjadBMbG0ORngyQLOjqh7sZnO_-ebIVfF

Trial registered on ANZCTR

Registration number

ACTRN12623001110673

Ethics application status

Approved

Date submitted

24/09/2023

Date registered

25/10/2023

Date last updated

4/04/2024

Date data sharing statement initially provided

25/10/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

A Phase II, Multicenter, Double-Blinded, Randomized, Placebo-Controlled, Parallel-Group, Single-Dose Study to Determine the Safety, Preliminary Efficacy, and Pharmacokinetics of ARG-007 in Acute Ischemic Stroke Patients

Scientific title

A Phase II, Multicenter, Double-Blinded, Randomized, Placebo-Controlled, Parallel-Group, Single-Dose Study to Determine the Safety, Preliminary Efficacy, and Pharmacokinetics of ARG-007 in Acute Ischemic Stroke Patients

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

SEANCON

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Stroke

Acute

Condition category

Condition code

Stroke

Ischaemic

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - ARG-007
Experimental: ARG-007 - Single intravenous infusion of ARG-007 0.3 mg/kg over 10 minutes, administered in hospital by registered nurse. Participants are to be administered the ARG-007 as soon after randomization as possible but before the completion of endovascular revascularization (using mechanical thrombectomy with or without thrombolysis).

Participants will be followed up in hospital on Day 2, Day 3, Day 6 (or Discharge), Safety assessments including vital signs, NIHSS and laboratory will be carried out during these visits. Additionally, an NCCT will be performed at day 2 and an MRI at day 3.

Following discharge participants will be followed up by telephone on Day 30, and Day 90 (End of Study [EoS]). Questionnaires will be collected during these visits to assess safety & efficacy.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Saline Placebo
There are no differences in procedures, activities, and/or processes between the intervention and placebo group.

Control group

Placebo

Outcomes

Primary outcome [1]

To evaluate the safety of a single dose of ARG-007 in participants with acute ischemic stroke (AIS).
The primary analyses will be mortality rate and frequency of AEs/SAEs.
Site personnel will collect AE information from participants. Open-ended
and nonleading questions will be used to enquire about any AEs/SAEs.

Timepoint [1]

Day 1, Day 2, Day 3, Day 6 or Discharge, Day 30 and Day 90 (Primary timepoint).

Secondary outcome [1]

The efficacy analysis is the difference in infarct volume between the ARG-007 and placebo groups as measured by MRI (or NCCT if MRI is not available) at 48 hours (Day 3 ± 1 day).

Timepoint [1]

Day 3 post-intervention.

Eligibility

Key inclusion criteria

1) Diagnosis of AIS deemed suitable for endovascular revascularization (mechanical thrombectomy with or without a thrombolytic agent).

2) Aged >/= 18 years.

3) Stroke onset (last known well) time < /= 24 hours before randomization.

4) The National Institutes of Health Stroke Scale (NIHSS) >/= 5 points at time of randomization.

5) Pre-stroke modified Rankin Score (mRS) < /= 3. Participant must have been living in their own home, apartment, or a senior’s lodge where no nursing care is required.

6) Confirmed symptomatic intracranial occlusion, based on computed tomographic angiography (CTA), at one or more of the following locations: intracranial internal carotid artery (T/L morphology) or M1 middle cerebral artery.

7) For participants transferring to stroke center from another hospital, CTA for study eligibility is to be performed or repeated at stroke center with endovascular suite onsite if there is a long delay (> 6 hours) from time of first CTA to time of repeat CTA.

8) Signed informed consent from participant or their legally authorized representative, or if required to enable inclusion by applicable national laws and regulations and the applicable Institutional Review Board/Ethics Committee requirements for obtaining consent from the investigator after consultation with an independent physician who is not otherwise participating in the study.

9) Willing (participant and/or caretaker) to commit to follow up assessments.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

1) Evidence of a large core of established infarction defined as ASPECTS of 0 to 5.

2) Evidence of intracranial hemorrhage or mass lesion on the qualifying imaging.

3) Endovascular revascularization procedure has already been completed at the time of Screening/randomization or has been completed before administration of study drug.

4) Planned use of an endovascular device that is not approved or does not have clearance by the relevant regulatory authority.

5) Rapid spontaneous improvement of neurological signs during Screening, as defined by a reduction of >/= 8 on the NIHSS between onset of symptoms and randomization.

6) History of stroke (ischemic or hemorrhagic) or penetrating head injury within 90 days before enrollment.

7) Uncontrolled blood pressure (BP) >/= 180/110 mmHg before endovascular revascularization procedure is initiated.

8) No femoral pulses, very difficult endovascular access, or extreme tortuosity of the great vessels that is predicted to result in an inability to timely deliver endovascular therapy. Direct common carotid or radial/brachial/axillary access is permissible.

9) Estimated or known body weight < 45 kg or > 130 kg.

10) Pregnancy: If a woman is of childbearing potential and has a positive point-of-care urine beta-human chorionic gonadotropin (ß-HCG) test or is breastfeeding.

11) Severe known renal impairment defined as requiring dialysis (hemo- or peritoneal) or a creatinine clearance < 29 mL/min.

12) Severe or fatal comorbid illness that will prevent improvement or follow-up.

13) Cannot complete follow-up visits because participant is a visitor to the area, or any other known reason that would prevent attendance at follow-up visits.

14) Received treatment with an investigational drug or device within 30 days before enrollment.

15) Any other condition that, in the opinion of the investigator, may adversely affect the safety of the participant, the participant’s ability to complete the study, or the outcome of the study.

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)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

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 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

13/03/2024

Actual

28/03/2024

Date of last participant enrolment

Anticipated

31/10/2025

Actual

Date of last data collection

Anticipated

30/01/2026

Actual

Sample size

Target

92

Accrual to date

3

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,WA,VIC

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [2]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [3]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [4]

Fiona Stanley Hospital - Murdoch

Recruitment hospital [5]

Sir Charles Gairdner Hospital - Nedlands

Recruitment hospital [6]

John Hunter Hospital - New Lambton

Recruitment hospital [7]

Liverpool Hospital - Liverpool

Recruitment hospital [8]

Royal Melbourne Hospital - Royal Park campus - Parkville

Recruitment hospital [9]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [10]

Gold Coast University Hospital - Southport

Recruitment postcode(s) [1]

5000 - Adelaide

Recruitment postcode(s) [2]

4102 - Woolloongabba

Recruitment postcode(s) [3]

3168 - Clayton

Recruitment postcode(s) [4]

6150 - Murdoch

Recruitment postcode(s) [5]

6009 - Nedlands

Recruitment postcode(s) [6]

2305 - New Lambton

Recruitment postcode(s) [7]

2170 - Liverpool

Recruitment postcode(s) [8]

3050 - Royal Melbourne Hospital

Recruitment postcode(s) [9]

4029 - Herston

Recruitment postcode(s) [10]

4215 - Southport

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Argenica Therapeutics Ltd

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Argenica Therapeutics Ltd

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

St. Vincent’s Hospital (Melbourne) Human Research Ethics Committee

Ethics committee address [1]

41 Victoria Parade, Fitzroy, VIC 3065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/07/2023

Approval date [1]

11/09/2023

Ethics approval number [1]

Summary

Brief summary

The primary purpose of this single dose study is to assess the safety and preliminary efficacy of ARG-007 in participants with AIS undergoing endovascular revascularization.

Trial website

Public notes

Contacts

Principal investigator

Name

Prof Graeme Hankey

Address

Perron Institute Chair in Stroke Research, RR Block, QE II Medical Centre, 8 Verdun St, Nedlands, WA 6009

Country

Australia

Phone

+61 8 6151 0828

Fax

Email

[email protected]

Contact person for public queries

Name

Dr Meghan Thomas

Address

Argenica Therapeutics Ltd, 4/117 Broadway Nedlands WA 6009, Australia PO Box 1458, West Perth WA 6872

Country

Australia

Phone

+61 8 9329 3396

Fax

Email

[email protected]

Contact person for scientific queries

Name

Dr Meghan Thomas

Address

Argenica Therapeutics Ltd, 4/117 Broadway Nedlands WA 6009, Australia. PO Box 1458, West Perth WA 6872

Country

Australia

Phone

+61 8 9329 3396

Fax

Email

[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

What supporting documents are/will be available?

No other documents available

Summary results

No Results