Acute Ischemic Stroke Interventional Study

NCT03803007 | Completed Phase 1 DMC

• 2 other identifiers: ACT-CS-0022018-002855-13
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

To assess safety of single IV (bolus + infusion) doses of ACT017 in patients with an acute ischemic stroke in addition to best emergency standard of care (including fibrinolysis by rtPA with or without added thrombectomy), with a specific focus on hemorrhage, whether clinically symptomatic (NIHSS score + 4 points or death, without other explanation), or seen (excluding other diagnoses) on 24-hour (hr) CT scan, serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), and medically important events and other safety items including biological and immunological tolerability.

Conditions

Acute Ischemic Stroke

Keywords

Haemorrhages; Thrombolysis; Thrombectomy; Anti-platelet; glenzocimab; ACT017; stroke; GPVI

Outcome Measures

Primary Outcomes (2)

• Symptomatic intracranial haemorrhages

  Number of participants experiencing a symptomatic haemorrhage defined by a secondary increase in National Institute Health Stroke Scale score by 4 points or greater, or death

  24 hours

• Incidence of non-symptomatic intracranial haemorrhages

  Non-symptomatic haemorrhages are those detected by Computerized Tomography scan

  24 hours

Secondary Outcomes (14)

• Change from baseline of National Institute Health Stroke Scale score (7 minimum, 42 maximum), brain lesions and vessel recanalization

  24 hours

• Change from baseline of National Institute Health Stroke Scale score (7 minimum, 42 maximum), brain lesions and vessel recanalization

  24 hours

• Change from baseline of modified Ranking Scale score assessment

  Day 90

• Change from baseline of modified Ranking Scale score assessment

  Day 90

• Change from baseline on size of infarct zone

  Day 7

Study Arms (2)

Intravenous glenzocimab (ACT017) 1000 mg

EXPERIMENTAL

Intravenous glenzocimab (ACT017) 1000 mg to be added to a tissue plasminogen activator +/- mechanical thrombectomy

Drug: Intravenous ACT017 1000 mg

Intravenous Placebo

PLACEBO COMPARATOR

Intravenous Placebo to be added to a tissue plasminogen activator +/- mechanical thrombectomy

Other: Intravenous Placebo

Interventions

Intravenous ACT017 1000 mg DRUG

Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms

Also known as: Thrombolysis by rtPA +/- thrombectomy

Intravenous glenzocimab (ACT017) 1000 mg

Intravenous Placebo OTHER

Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms

Also known as: Thrombolysis by rtPA +/- thrombectomy

Intravenous Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time of randomization). Extreme caution should be exercised in patients over 80 years of age with regards their general health, neurological status and any concomitant diseases and treatments that are likely to be more common;
• Patients who have given written consent, legal representative consent or emergency consent (including e-consent) in accordance with local legal and IECs/IRBs requirements;
• Patients presenting with an acute disabling ischemic stroke in either the anterior or posterior circulation.The time of onset is known or if unknown, the last time the patient was seen well, was at most 4.5 hrs before confirmation of the diagnosis enabling the initiation of alteplase administration within this time-frame;
• Patients presenting at least a NIHSS ≥ 6 prior to thrombolysis with tPA;
• Patients eligible for, or administered thrombolysis treatment with tPA;
• Patients who can undergo mechanical thrombectomy if eligible;
• Patients affiliated to social security insurance (if applicable, in accordance to local regulations);
• Effective birth control method should be used for at least the next 2 months by women, and 4 months by men after IMP administration; birth control methods considered to be highly effective include:
• intrauterine device
• intrauterine hormone-releasing system
• bilateral tubal occlusion
• vasectomized partner
• sexual abstinence (if applicable in accordance to local regulations)
• Women of child-bearing potential must undergo a urinary or plasma pregnancy test with negative results;

You may not qualify if:

• Coma, and/or NIHSS \>25;
• Patients \< 18 years of age;
• Prior ischemic stroke within the past 3 months with pre-stroke mRS known to be \> 2;
• Baseline CT-scan evaluation: more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline imaging;
• Significant mass effect with midline shift;
• Stroke of hemorrhagic origin;
• Contra-indications to thrombolysis with tPA:
• Patients with known hypersensitivity to the active substance alteplase or to any of its excipients;
• Patients with a high risk of hemorrhages:
• significant bleeding disorder at present or within the past 6 months;
• known haemorrhagic diathesis (episodes within past 6 months);
• patients receiving effective oral anticoagulant treatment, e.g. warfarin sodium;
• manifest or recent severe or dangerous bleeding;
• known history of or suspected intra-cranial haemorrhage;
• any history of central nervous system lesion (i.e. trauma, intra-parenchymal neoplasm, unsecured aneurysm, intracranial or spinal surgery, vascular malformation etc..);

Sponsors & Collaborators

• Acticor Biotech: lead

Study Sites (1)

Centre Hospitalier Universitaire de Bordeaux,

Bordeau, 33404, France

Location

Related Publications (3)

• Voors-Pette C, Lebozec K, Dogterom P, Jullien L, Billiald P, Ferlan P, Renaud L, Favre-Bulle O, Avenard G, Machacek M, Pletan Y, Jandrot-Perrus M. Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab. Arterioscler Thromb Vasc Biol. 2019 May;39(5):956-964. doi: 10.1161/ATVBAHA.118.312314.

  PMID: 31017822 BACKGROUND

• Renaud L, Lebozec K, Voors-Pette C, Dogterom P, Billiald P, Jandrot Perrus M, Pletan Y, Machacek M. Population Pharmacokinetic/Pharmacodynamic Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen-Induced Platelet Aggregation. J Clin Pharmacol. 2020 Sep;60(9):1198-1208. doi: 10.1002/jcph.1616. Epub 2020 Jun 4.

  PMID: 32500636 BACKGROUND

• Mazighi M, Kohrmann M, Lemmens R, Lyrer PA, Molina CA, Richard S, Toni D, Pletan Y, Sari A, Meilhoc A, Jandrot-Perrus M, Binay S, Avenard G, Comenducci A, Grouin JM, Grotta JC; ACTIMIS Study Group. Safety and efficacy of platelet glycoprotein VI inhibition in acute ischaemic stroke (ACTIMIS): a randomised, double-blind, placebo-controlled, phase 1b/2a trial. Lancet Neurol. 2024 Feb;23(2):157-167. doi: 10.1016/S1474-4422(23)00427-1.

  PMID: 38267188 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Hemorrhage; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andrea Comenducci, MD

  Acticor Biotech

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The phase Ib of the study with a sequential design has been achieved (5 arms). The second phase IIa is ongoing. The selected dose (1000mg) for this second part will be compared to placebo (2 arms) with a parallel design.

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: January 14, 2019
• Study Start: March 6, 2019
• Primary Completion: September 27, 2021
• Study Completion: September 27, 2021
• Last Updated: October 6, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)