The Androtriol Injection for the Treatment of Acute Ischemic Stroke

A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IIb Clinical Trial of Androtriol Injection for the Treatment of Acute Ischemic Stroke

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, phase IIb clinical trial of Androtriol injection for the treatment of acute ischemic stroke. The goal of this trial is to explore the efficacy and safety of different doses of Androtriol injection in patients with acute ischemic stroke (AIS) who received vascular recanalization treatment within 24 hours of symptom onset.

Participants will receive a low-dose Androtriol injection (100 mg BID), a high-dose Androtriol injection (300 mg BID), or a placebo intravenously within 24 hours of stroke onset. They will be treated twice daily (every 12 hours) for 7 days, with a total of 14 doses over the course of the study. Each infusion will last approximately 30±5 minutes.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Androtriol Injection (High-dose group); Drug: Androtriol Injection (Low-dose group); Drug: Hydroxypropyl-β-cyclodextrin injection

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shuya Li, MD; Phone Number: 86-10-59976117; Email: shuyali85@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18- 80 years, male or female；
2. mRS score ≤1 prior to this onset;
3. Planning to receive or have received intravascular recanalization therapy at our center within 24h of onset;
4. To complete the first administration of the investigational medication within 24h of onset;
5. NIHSS（National Institutes of Health Stroke Scale）score≥6 prior to intravascular recanalization;
6. Informed consent.

Exclusion Criteria:

1. Intracranial hemorrhagic diseases, including hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc.;
2. Severe disorders of consciousness: NIHSS 1a≥2 points;
3. Large infarct core (ASPECTS <6, or>1/3 of MCA territory involved, as evidenced by CT or MRI);
4. Severe hypertension: systolic blood pressure ≥185mmHg or diastolic blood pressure ≥110mmHg after medication control;
5. History of severe kidney disease (such as dialysis), or eGFR <45 mL/min/1.73m²;
6. History of severe liver disease, or ALT, AST levels more than 3 times of the upper limit of normal, or bilirubin more than 3 times of the upper limit of normal;
7. Cardiovascular diseases, such as complete atrioventricular block, history of congestive heart failure (CHF), or heart function classification≥NYHA Class III;
8. Critically ill patients with an expected lifespan≤90 days;
9. History of epilepsy or epilepsy-like symptoms during stroke or severe psychiatric disorders, intellectual disability, or dementia;
10. History of intracranial hemorrhage;
11. Severe injury or surgery history within 3 months of onset;
12. Have received>1 dose of neuroprotective drugs after this onset, such as edaravone, edaravone dexborneol injection, ginkgo lactone, ginkgo diterpene glucamine，etc;
13. Allergy to the investigational drug (either the active ingredient androtriol or the excipient hydroxypropyl beta-cyclodextrin) or similar chemical structure drugs;
14. Pregnant or breastfeeding;
15. Participation in other clinical trials within 3 months of onset;
16. Unsuitable for participating in this study judged by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group (high-dose group); Androtriol injection (300 mg BID)	Drug: Androtriol Injection (High-dose group); Participants will receive 30 mL of Androtriol Injection per dose, administered every 12 hours for 7 consecutive days. Each infusion will be administered over a period of 30±5 minutes.
Experimental: Intervention Group (low-dose group); Androtriol injection (100 mg BID)	Drug: Androtriol Injection (Low-dose group); Participants will receive 10 mL of Androtriol Injection combined with 20 mL of placebo (Hydroxypropyl Beta-Cyclodextrin Injection) per dose, administered every 12 hours for 7 consecutive days. Each infusion will be administered over a period of 30±5 minutes.
Placebo Comparator: Placebo; Hydroxypropyl-β-cyclodextrin injection	Drug: Hydroxypropyl-β-cyclodextrin injection; Participants will receive 30 mL of Hydroxypropyl-β-cyclodextrin injection per dose, administered every 12 hours for 7 consecutive days. Each infusion will be completed within 30±5 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with a modified Rankin Scale (mRS) score of 0-1 at 90 days after stroke onset	The mRS denotes modified Rankin Scale, ranging from 0 (no neurologic deficit, no symptoms or completely recovered) to 6 (death).	90 days after stroke onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The modified Rankin Scale (mRS) scores at 90 days after stroke	The mRS denotes modified Rankin Scale, ranging from 0 (no neurologic deficit, no symptoms or completely recovered) to 6 (death).	90 days after stroke onset
The proportion of participants with a modified Rankin Scale (mRS) score of 0-2 at 90 days after stroke onset	The mRS denotes modified Rankin Scale, ranging from 0 (no neurologic deficit, no symptoms or completely recovered) to 6 (death).	90 days after stroke onset
The change of the National Institutes of Health Stroke Scale (NIHSS) score from baseline at 14 days after stroke onset or at discharge	Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe stroke.	Baseline, 14 days or at discharge
The change of Barthel Index (BI) scores at 30 days and 90 days after stroke onset	The Barthel Index for Activities of Daily Living (ADL) assesses functional independence, generally in stroke patients. The higher the score, the more independent the patient is in completing the measured ADLs.	Baseline, 30 days and 90 days after stroke onset
The change of EuroQol Five Dimensions Questionnaire (EQ-5D) scores at 30 days and 90 days after stroke onset	The EQ-5D assesses quality of life across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain is scored on a scale from 1 to 3, with lower scores (closer to 1) indicating better health outcomes.	Baseline, 30 days and 90 days after stroke onset

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AE) and treatment-related adverse events (TEAE)		From the time of administration to day 90
Incidence of significant adverse events and serious adverse events (SAE)		From the time of administration to day 90
Symptomatic intracranial hemorrhage (sICH) within 36 hours after thrombolysis (SITS-MOST criteria)	The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria: Within 36 hours after thrombolysis, an increase of NIHSS score≥4 compare to baseline or the lowest NIHSS, with > 30% infarction area.	36 hours after thrombolysis
All-cause mortality		From the time of administration to day 90
Discontinuation of medication due to any reason or adverse events		From the time of administration to day 90
The change of midline shift from baseline at 22-36 hours and 7 days after first treatment		Baseline, 22-36 hours, and 7 days after first treatment
The change of lesion volume from baseline at 22-36 hours and 7 days after first treatment		Baseline, 22-36 hours, and 7 days after first treatment
The change of edema volume on the lesion side from baseline at 22-36 hours and 7 days after first treatment		Baseline, 22-36 hours, and 7 days after first treatment

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 31, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): October 30, 2025

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Estimated): November 7, 2024

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke; Androtriol
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia
• Other Study ID Numbers: YC-6-PIIb-AIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No