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Adaptive Efficacy and Safety Study of Glenzocimab Used as an add-on Therapy on Top of Standard of Care un the 4.5 Hours Following an Acute Ischemic Stroke (ACTISAVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05070260
Recruitment Status : Recruiting
First Posted : October 7, 2021
Last Update Posted : September 30, 2022
Sponsor:
Information provided by (Responsible Party):
Acticor Biotech

Brief Summary:

A randomized, double blind, multicenter, multinational, placebo controlled, parallel group, single dose, adaptive phase II/III study (respectively Part 1 and 2).

The study evaluates the efficacy and safety of a fixed dose of glenzocimab (1000 mg IV over 6 hrs including initial bolus of 15 minutes) on top of the best standard of care.


Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Drug: Intravenous glenzocimab (ACT017) 1000 mg Drug: Intravenous Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomized, double blind, multicenter, multinational, placebo controlled, parallel group, single dose, adaptive phase II/III study (respectively Part 1 and 2).
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double blind
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Multicenter, Multinational, Placebo Controlled, Parallel Group, Single Dose, Adaptive Efficacy and Safety Study of Glenzocimab Used as an add-on Therapy on Top of Standard of Care un the 4.5 Hours Following an Acute Ischemic Stroke
Actual Study Start Date : September 23, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : December 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ischemic Stroke

Arm Intervention/treatment
Experimental: Intravenous glenzocimab (ACT017) 1000 mg
Intravenous glenzocimab (ACT017) 1000 mg to be added to a tissue plasminogen activator +/- mechanical thrombectomy
Drug: Intravenous glenzocimab (ACT017) 1000 mg
Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms
Other Name: Thrombolysis by rtPA +/- thrombectomy

Placebo Comparator: Intravenous Placebo
Intravenous Placebo to be added to a tissue plasminogen activator +/- mechanical thrombectomy
Drug: Intravenous Placebo
Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms
Other Name: Thrombolysis by rtPA +/- thrombectomy




Primary Outcome Measures :
  1. Ordinal modified Rankin Scale (mRS) [ Time Frame: Day 90 ]
    To show the efficacy of glenzocimab vs. placebo, on at least one of the 2 dual endpoints, i.e. the ordinal modified Rankin Scale (mRS) assessed at Day 90 or the binary poor outcome defined as a mRS score of 4-6 assessed at Day 90, either in the overall population (denoted as OP) or in the subgroup of patients who received Mechanical Thrombectomy (denoted as MT+).

  2. Binary Poor Outcome on the mRS scale [ Time Frame: Day 90 ]
    Binary Poor Outcome on the mRS scale defined by a score of 4-6 at Day 90


Secondary Outcome Measures :
  1. Efficacy of glenzocimab vs. placebo [ Time Frame: Day 90 ]
    To show the efficacy of glenzocimab vs. placebo on the all-cause mortality at day-90 either in the OP or in the subgroup of patients who received MT+.

  2. Ordinal modified Ranking Scale (mRS) [ Time Frame: Day 90 ]
    To assess the favorable responses defined as mRS score of 0-1 To assess the good responses defined as mRS score 0-2

  3. Utility Weighted mRS [ Time Frame: Day 90 ]
    To assess the utility weighted mRS (UW-mRS)

  4. Neurological Status Change as assessed by NIHSS value compared to pre-IVT value [ Time Frame: 24 hours ]

    Response defined by a relative decrease (%) in NIHSS value at 24 hours compared to pre-IVT value higher than 30%.

    Relative change (%) in NIHSS value at 24 hrs compared to pre-IVT value


  5. Recanalization rate [ Time Frame: Day 90 ]
    To assess recanalization in patients undergoing thrombectomy by eTICI score

  6. Cerebral tissue reperfusion [ Time Frame: Day 90 ]
    To assess Cerebral tissue reperfusion

  7. Infarct volume progression and hemorrhagic transformation [ Time Frame: 24 hrs ]
    To assess the impact on follow up imaging (follow up infarct volume, infarct growth and volume of hemorrhagic transformation)

  8. Measure of Quality of Life by EuroQol-5 Dimension-5 Level (EQ-5D-5L) [ Time Frame: Day 90 ]
    Quality of Life as assessed by the EuroQol-5 Dimension-5 Level. A Quality-of-Life Scale (EQ-5D-5L)

  9. Incidence of Deaths [ Time Frame: Day 90 ]
    Deaths within the first 24 hours and over the whole study period until Day 90 (Kaplan-Meier curve)

  10. Incidence of Symptomatic intracranial hemorrhages [ Time Frame: 24 hours ]
    Symptomatic intracranial hemorrhages, defined by both anatomical imaging (according to Heidelberg's classification) AND an increase in NIHSS score by 4 points or greater, or death that is not explained otherwise (according to ECASS III study definition)

  11. Incidence of Non-symptomatic hemorrhages [ Time Frame: 24 hours ]
    Non-symptomatic hemorrhages, seen on 24-hours plain CT-Scan, not present at baseline assessment, once other diagnoses are excluded

  12. Incidence of Adverse Events, SAEs, bleeding-related events, and Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 90 ]
    Incidence, nature and severity of Adverse Events, SAEs, bleeding-related events, and Treatment-Emergent Adverse Events (TEAEs)

  13. Change in vital signs (Blood Pressure) at any visit or discharge as compared to Baseline [ Time Frame: 24 hours ]
    Blood Pressure will be assessed every 30 minutes during the 6 hours (infusion) then every 3 hours up to 24 hours.

  14. Change in vital signs (Heart Rate) at any visit or discharge as compared to Baseline [ Time Frame: 24 hours ]
    Heart Rate will be assessed every 30 minutes during the 6 hours (infusion) then every 3 hours up to 24 hours

  15. Change in hematology assessments: RBC (Red Blood Cell Count) at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in RBC (Red Blood Cell Count) in million/mm3

  16. Change in hematology assessments: RBC (Red Blood Cell Count) at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in RBC (Red Blood Cell Count) in million/mm3

  17. Change in hematology assessments: Hemoglobin at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Hemoglobin in g/100ml

  18. Change in hematology assessments: Hemoglobin at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Hemoglobin in g/100ml

  19. Change in hematology assessments: Hematocrit at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Hematocrit in %

  20. Change in hematology assessments: Hematocrit at 24 hours at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Hematocrit in %

  21. Change in hematology assessments: Mean Corpuscular Hemoglobin Volume (MCV) at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Mean Corpuscular Hemoglobin Volume (MCV) in µ3

  22. Change in hematology assessments: Mean Corpuscular Hemoglobin Volume (MCV) at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Mean Corpuscular Hemoglobin Volume (MCV) in µ3

  23. Change in hematology assessments: Mean corpuscular hemoglobin content (MCHC) at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Mean corpuscular hemoglobin content (MCHC) in pg

  24. Change in hematology assessments: Mean corpuscular hemoglobin content (MCHC) at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Mean corpuscular hemoglobin content (MCHC) in pg

  25. Change in hematology assessments: Corpuscular hemoglobin concentration (CHC) at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Corpuscular hemoglobin concentration (CHC) in %

  26. Change in hematology assessments: Corpuscular hemoglobin concentration (CHC) at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Corpuscular hemoglobin concentration (CHC) in %

  27. Change in hematology assessments: Leucocytes(/mm3) at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Leucocytes in /mm3

  28. Change in hematology assessments: Leucocytes(/mm3) at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Leucocytes in /mm3

  29. Change in hematology assessments: Platelets x 10^9 /L at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Platelets x 10^9 /L

  30. Change in hematology assessments: Platelets x 10^9 /L at 24 hours at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Platelets x 10^9 /L

  31. Change biochemistry assessments : SGPT (Sérum Glutamate Pyruvate Transaminase) at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in SGPT in UI/L

  32. Change biochemistry assessments : SGPT at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in SGPT in UI/L

  33. Change biochemistry assessments : SGOT at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in SGOT in UI/L

  34. Change biochemistry assessments : SGOT at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in SGOT in UI/L

  35. Change biochemistry assessments: LDH at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in LDH in UI/l

  36. Change biochemistry assessments : LDH at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in LDH in UI/l

  37. Change biochemistry assessments : Cholesterol at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Cholesterol in g/L or mmol/L

  38. Change biochemistry assessments : Cholesterol at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Cholesterol in g/L or mmol/L

  39. Change biochemistry assessments : Triglycerid at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Triglycerid in g/L or mmol/L

  40. Change biochemistry assessments : Triglycerid at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Triglycerid in g/L or mmol/L

  41. Change biochemistry assessments : Urea at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Urea in g/L or mmol/L

  42. Change biochemistry assessments : Urea at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Urea in g/L or mmol/L

  43. Change biochemistry assessments : Creatinin at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Creatinin in mg/L or µM/L

  44. Change biochemistry assessments : Creatinin at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Creatinin in mg/L or µM/L

  45. Change biochemistry assessments : GFR at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in GFR in mL/min/1,73 m²

  46. Change biochemistry assessments : GFR at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change inGFR in mL/min/1,73 m²

  47. Change biochemistry assessments : Serum Glucose at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Serum Glucose in g/L

  48. Change biochemistry assessments : Serum Glucose at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Serum Glucose in g/L

  49. Change biochemistry assessments : D-Dimer at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in D-Dimer in µg/L

  50. Change biochemistry assessments : D-Dimer at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in D-Dimer in µg/L

  51. Change biochemistry assessments : Fibrinogen at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Fibrinogen in g/L

  52. Change biochemistry assessments : Fibrinogen at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Fibrinogen in g/L

  53. Change biochemistry assessments : INR score at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in INR Score

  54. Change biochemistry assessments : INR score at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in INR Score

  55. Change biochemistry assessments : PT score at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in PT in sec

  56. Change biochemistry assessments : PT score at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in PT in sec

  57. Change biochemistry assessments : aPTT score at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in aPTT in sec

  58. Change biochemistry assessments : aPTT score at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in aPTT in sec

  59. Change in dipstick urinalysis assessments: Turbidity at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Change in urinalysis assessments

  60. Change in dipstick urinalysis assessments: pH at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Change in urinalysis assessments

  61. Change in dipstick urinalysis assessments: Glucose at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Change in urinalysis assessments

  62. Change in dipstick urinalysis assessments: Proteins at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Change in urinalysis assessments

  63. Change in dipstick urinalysis assessments: Blood at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Change in urinalysis assessments

  64. Change in dipstick urinalysis assessments: Leucocytes at 24 hours as compared to Baseline [ Time Frame: 24 hours ]
    % of patient with change in Change in urinalysis assessments

  65. Change in dipstick clinical laboratory assessments (urinalysis) at Day 7 or discharge as compared to Baseline [ Time Frame: Day 7 ]
    % of patient with change in Change in urinalysis assessments

  66. Change in coagulation parameters (INR, PT, a PTT) [ Time Frame: 24 hours ]
    Change in coagulation parameters (INR, PT, aPTT) at 24 hrs

  67. ECG changes [ Time Frame: 24 hours ]
    ECG change from baseline on QT, QTc, PR, ST and QRS intervals at 24 hours as compared to Baseline

  68. ECG changes [ Time Frame: Day 7 ]
    ECG change from baseline on QT, QTc, PR, ST and QRS intervals at Day 7 as compared to Baseline

  69. ECG changes [ Time Frame: Day 90 ]
    ECG change from baseline on QT, QTc, PR, ST and QRS intervals at discharge as compared to Baseline


Other Outcome Measures:
  1. Imaging for exploratory endpoints [ Time Frame: Baseline ]
    • Acute ischemic stroke diagnosis and occluded cerebral vessel identification assessed by CTA or MRA/MRI with Time of Flight (TOF) sequence at Baseline

  2. Imaging for exploratory endpoints [ Time Frame: 24 hours ]
    Non Symptomatic and Symptomatic intracranial hemorrhage detection assessed by CTA or MRA or MRI+TOF at the time of its occurrence, followed by a plain CT-scan or MRI at 24h



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time of randomization)
  2. Having given their own written consent, or legal representative consent, or emergency consent, and in any case, in strict accordance with country-specific legal requirements,
  3. Presenting with an acute disabling ischemic stroke either in the anterior or in posterior circulation, with or without visible occlusion, with a known time of onset, that is ≤ 4.5 hrs
  4. Presenting with a pre-IVT NIHSS ≥ 6
  5. In whom thrombolysis with tPA is or has been initiated, whether or not patients are additionally eligible to mechanical thrombectomy (MT+ alteplase)
  6. Women of childbearing potential (WOCBP) must have a negative serum/urine pregnancy test at baseline. Women of childbearing potential, i.e., fertile, are defined as women following menarche and until becoming post-menopausal unless permanently sterile, i.e., having undergone hysterectomy, bilateral salpingectomy and bilateral oophorectomy
  7. Post-menopausal women defined as not having menses for 12 months without an alternative medical cause. For WOCBP, a highly effective birth control method should be in place that can achieve a failure rate of less than 1% per year that should last for at least 2 months after IMP administration.

    Birth control methods which may be considered as highly effective in WOCBP include:

    • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (intravaginal, transdermal),
    • progestogen-only hormonal contraception associated with inhibition of ovulation (injectable, implantable)
    • intrauterine device (IUD),
    • intrauterine hormone-releasing system (IUS),
    • bilateral tubal occlusion,
    • vasectomized partner,

    Birth control methods which may be considered as highly effective for men and that should last for 4 months after IMP administration include:

    • vasectomy,
    • use of condom combined with a highly effective birth control method for their WOCBP partner.

    Please note that hormonal contraception is a risk factor for thromboembolic events and attention should be called to reconsider it passed the acute stroke phase.

  8. Patients affiliated to a health insurance - modality depending on country legal requirement

Exclusion Criteria:

  1. Coma, or NIHSS >25,
  2. Patients < 18 years,
  3. Protected adults under guardianship or curatorship,
  4. Prior ischemic stroke within the past 3 months,
  5. mRS pre-stroke known to be ≥ 2,
  6. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on Baseline Computed Tomography Angiography (CTA) or Magnetic Resonance Imaging (MRI) or with vascular injection (MRA),
  7. Significant mass effect with midline shift,
  8. Stroke of hemorrhagic origin,
  9. Patients likely to require dual antiplatelet therapy (DAPT) within the first 24 hrs after cessation of glenzocimab or placebo infusion for e.g., carotid stenting,
  10. Known renal insufficiency (Grades 4-5 - severe or terminal),
  11. Known allergic reaction to contrast agents,
  12. Patients under anti-coagulant therapy, except preventative doses of injectable low molecular weight heparin (LMWH),
  13. Known ongoing treatment with a mAb,
  14. Prior cardiopulmonary resuscitation < 10 days,
  15. Childbirth within < 10 days,
  16. Seizures at stroke onset if it precludes obtaining an accurate baseline (pre-IVT) NIHSS,
  17. Life expectancy (except for stroke) < 3 months,
  18. Pregnancy or breastfeeding,
  19. Females of childbearing potential not using effective birth control methods,
  20. Known current participation in another clinical investigation with experimental drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05070260


Contacts
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Contact: Andrea Comenducci, MD +33631003997 andrea.comenducci@acticor-biotech.com
Contact: Yannick PLETAN, MD +33685946370 yannick.pletan@acticor-biotech.com

Locations
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United States, Texas
Memorial Hermann Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: James Grotta, MD         
Germany
University Clinic Essen Recruiting
Essen, Germany, 45147
Contact: Martin Köhrmann, MD         
Sponsors and Collaborators
Acticor Biotech
Investigators
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Study Director: Andrea Comenducci, MD Acticor Biotech
Additional Information:
Publications:
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Responsible Party: Acticor Biotech
ClinicalTrials.gov Identifier: NCT05070260    
Other Study ID Numbers: ACT-CS-005
First Posted: October 7, 2021    Key Record Dates
Last Update Posted: September 30, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Acticor Biotech:
Haemorrhages GPVI
Thrombolysis
Thrombectomy
Anti-platelet
glenzocimab
ACT017
stroke
GPVI
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Infarction
Necrosis
Glenzocimab
Anticoagulants