An Open-label Phase 2b Study with Blinded Evaluation of the Combination of Amodiaquine and Potassium Canrenoate with Exenatide or Glibenclamide in Acute Ischemic Stroke

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genesis Pharma S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genesis Pharma S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To evaluate the safety of the investigational treatment compared to best medical therapy (BMT), on hemorrhagic transformation.

Secondary objectives 10

1. To evaluate the impact of the investigational treatment compared to BMT on the degree of disability in patients with stroke
2. To evaluate the impact of the investigational treatment, compared to BMT, on the final infarct volume.
3. To evaluate the impact of the investigational treatment, compared to BMT on recanalization of the occluded vessel
4. To assess the impact of the investigational treatment, compared to BMT, on the impairment caused by the stroke as assessed by various aspects of brain function
5. To evaluate the safety and tolerability of study intervention
6. To assess the impact of the investigational treatment, compared to BMT, on all-cause mortality
7. To assess the impact of the investigational treatment on the development of depression following the stroke
8. To assess the impact of the investigational treatment compared to BMT, on the levels of selected biomarkers
9. To assess plasma levels of the investigational combination treatments
10. To evaluate the correlation between the plasma concentrations of investigational combination treatments with the safety, response, and compliance to treatment

Conditions and MedDRA coding

Acute Ischemic Stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Aged 18 to 80 years, inclusive, at the time of signing the informed consent.
2. Confirmed diagnosis of AIS, according to the World Health Organization (WHO) definition, as diagnosed with CT.
3. Radiology-confirmed supratentorial IS; nonlacunar, >15 mm diameter in one direction as depicted in the CT scan.
4. NIHSS score at screening ≥5 and ≤20 points.
5. A maximum of 36 h may elapse from symptoms’ onset to treatment initiation.
6. Pre-stroke (36 hours prior to stroke onset) independent functional status in activities of daily living (ie, patients must have been living without requiring nursing care) based on information provided by the patient or his/her caregivers.
7. Patient not a candidate for thrombolysis with tPA.
8. Patient not a candidate for thrombectomy.
9. A diabetic patient must have been on a stable antidiabetic regimen at least 8 weeks before inclusion in the study.
10. Patient with either no history of depression or treated for depression with a stable combination of antidepressants for at least 8weeks before inclusion in the study.
11. Patient with no known history of dementia.
12. Provision of signed informed consent by the patient or caregiver/legal representative, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
13. Expectation that the patient will receive standard physical, occupational, and speech rehabilitation therapies as indicated for post-stroke deficits.
14. Patient or caregivers understand study procedures and are willing to comply with them for the entire length of the study.

Exclusion criteria 17

1. Allergy/sensitivity to study drugs or their ingredients.
2. Current drug or alcohol use or dependence that, in the opinion of the site Investigator, would interfere with adherence to study requirements.
3. Inability or unwillingness of patient or caregiver/legal guardian/representative to give written informed consent.
4. Pregnancy or lactation, at screening.
5. Patient who plans to become pregnant within 6 months, or women in childbearing age with negative pregnancy test but who refuses to accept contraception.
6. Patient unlikely to be available for a 90-day follow-up (eg, life expectancy <3 months).
7. Patients with contraindications with the combination of the drugs being studied.
8. Clinical presentation of a lacunar stroke according to site investigators.
9. Patient suffering from intracranial tumors, severe trauma, encephalitis, subarachnoid hemorrhage, or other brain organic diseases.
10. Patient presenting with uncontrolled hypertension, blood glucose level >4 mmol/L, cancer, renal failure (defined as creatinine clearance <90 ml/min), evidence of acute myocardial infarction, acute pancreatitis, or other significant medical condition according to Investigator’s opinion.
11. Mental illness or psychiatric disease making the patient incapable of following/participating in this study, as assessed by the Investigator.
12. a. Alanine transaminase (ALT) [or aspartate transaminase (AST)] >2.0 x upper limit of normal (ULN) b. Total bilirubin >1.5xULN (Participants with Gilbert’s syndrome can be included with total bilirubin >1.5 x ULN as long as direct bilirubin is ≤1.5 x ULN) c. Current or chronic history of liver disease.
13. Concurrent treatment with any of the investigational drugs in this study.
14. Participation in other clinical trials within 30 days before randomization, or currently involved in other clinical trials.
15. Signs of intracranial hemorrhage or suspected subarachnoid hemorrhage, as assessed based on CT imaging examination.
16. Presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency (previously known or as confirmed at the clinical site).
17. Treatment with medications/agents which are contraindicated based on the SmPCs of the combination IMPs for usage in combination with the study interventions.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients with hemorrhagic transformation as depicted in a CT or MRI.

Secondary endpoints 10

1. Degree of disability based on the mRS score
2. • Infarct volume defined as MRI lesion volume on Day 5 • Infarct volume defined as MRI lesion volume on Day 90 • Change in DWI lesion volume from Day 5 to Day 90, based on MRI • Change in PWI lesion volume from Day 5 to Day 90, based on MRI
3. Change in recanalization of the occluded vessel based on MR angiography (MRA).
4. Percentage of patients with clinically meaningful improvement in NIHSS score (improvement >4 points).
5. • Percentage of patients treated with investigational combination therapy on top of BMT and those treated with BMT only, experiencing all-cause on-treatment AEs, analyzed for: o patients that complete the study period, and o patients who discontinue from the study period due to an AE. • Percentage of patients with abnormal clinically significant laboratory test results.
6. All-cause mortality.
7. • Percentage of patients who developed depression, defined as score >10 on the HAM-D17 • Percentage of patients who developed mild to moderate depression (HAM-D17 score: 14-17), or moderate to severe depression (HAM-D17 score: >17).
8. Percentage of change in blood biomarkers.
9. • Observed plasma concentration • Minimum observed plasma concentration at steady state conditions
10. Correlation of plasma concentrations of the investigational combination treatments with: • The percentage of patients experiencing overall AEs and specific AEs • Degree of disability based on the mRS score • The percentage of patients who developed depression • The percentage of patients with clinically meaningful improvement in NIHSS score • MRI response parameters • Biomarker levels • Treatment compliance

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genesis Pharma S.A.

Sponsor organisation

Genesis Pharma S.A.

Address

Kifissias Leoforos 270

City

Chalandri

Postcode

152 32

Country

Greece

Scientific contact point

Organisation

Genesis Pharma S.A.

Contact name

Georgios Karachalios

Public contact point

Organisation

Genesis Pharma S.A.

Contact name

Georgios Karachalios

Third parties 7

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications