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Acute Ischemic Stroke Interventional Study (ACTIMIS)

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: NCT03803007
Recruitment Status : Not yet recruiting
First Posted : January 14, 2019
Last Update Posted : January 23, 2019
Sponsor:
Collaborators:
Orion Corporation, Orion Pharma
Axial Biotech, Inc
QPS
Information provided by (Responsible Party):
Acticor Biotech

Tracking Information
First Submitted Date  ICMJE December 12, 2018
First Posted Date  ICMJE January 14, 2019
Last Update Posted Date January 23, 2019
Estimated Study Start Date  ICMJE January 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • Symptomatic intracranial haemorrhages [ Time Frame: 24 hours ]
    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
  • Incidence of non-symptomatic intracranial haemorrhages [ Time Frame: 24 hours ]
    Non-symptomatic haemorrhages are those detected by Computerized Tomography scan
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • Change from baseline of National Institute Health Stroke Scale score (7 minimum, 42 maximum), brain lesions and vessel recanalization [ Time Frame: 24 hours ]
    Absolute change from baseline of National Institute Health Stroke Scale score, change from baseline on brain lesions as assessed by Computerized Tomography scan or Magnetic Resonance Imaging or Magnetic Resonance Angiography, change from baseline on Recanalization as measured by the modified Thrombolysis In Cerebral Infarction score (0 minimum, 3 maximum) on Magnetic Resonance Angiography
  • Change from baseline of National Institute Health Stroke Scale score (7 minimum, 42 maximum), brain lesions and vessel recanalization [ Time Frame: 24 hours ]
    Relative (%) change from baseline of National Institute Health Stroke Scale score, change from baseline on brain lesions as assessed by Computerized Tomography scan or Magnetic Resonance Imaging or Magnetic Resonance Angiography, change from baseline on Recanalization as measured by the modified Thrombolysis In Cerebral Infarction score (0 minimum, 3 maximum) on Magnetic Resonance Angiography
  • Change from baseline of modified Ranking Scale score assessment [ Time Frame: Day 90 ]
    modified Ranking Scale score (0 minimum and 6 maximum): number of patients with favorable outcome (score 0-2)
  • Change from baseline of modified Ranking Scale score assessment [ Time Frame: Day 90 ]
    modified Ranking Scale score (0 minimum and 6 maximum): percentage of patients with favorable outcome (score 0-2)
  • Change from baseline on size of infarct zone [ Time Frame: Day 7 ]
    Change from baseline on size of infarct zone assessed by a central Magnetic Resonance Imaging review
  • Change from baseline on vital signs [ Time Frame: 6 hours, 24 hours, Day 7, Day 30 and Day 90 ]
    Change from baseline on systolic and diastolic blood pressure
  • Change from baseline on vital signs [ Time Frame: 6 hours, 24 hours, Day 7, Day 30 and Day 90 ]
    Change from baseline on heart rate
  • Change from baseline on clinical laboratory assessments [ Time Frame: Day 90 ]
    Change from baseline on plasma haemoglobin level
  • Change from baseline on clinical laboratory assessments [ Time Frame: Day 90 ]
    Change from baseline on platelet count
  • Change from baseline on clinical laboratory assessments [ Time Frame: Day 90 ]
    Change from baseline on serum glucose concentration
  • Change from baseline on clinical laboratory assessments [ Time Frame: Day 90 ]
    Change from baseline on serum creatinine concentration
  • Change from baseline on ElectroCardioGram (ECG) [ Time Frame: 24 hours and Day 90 ]
    Change from baseline on 12-lead ElectroCardioGram (ECG)
  • Evidence of anti-ACT017 antibodies (ADA) [ Time Frame: Day 30 and Day 90 ]
    To assess evidence of anti-ACT017 antibodies (ADA) as a possible to ACT017 administration
  • Pharmacokinetics on ACT017 plasma concentration [ Time Frame: 30 minutes, 9 hours and 24 hours ]
    Change from baseline on ACT017 plasma concentration
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Acute Ischemic Stroke Interventional Study
Official Title  ICMJE Randomized, Double Blind, Multicenter, Multinational, Placebo Controlled, Single Parallel Escalating Dose, Safety & Efficacy Study of ACT017 Used as add-on of SoC Therapy in the 4,5 Hrs Post Onset of Acute Ischemic Stroke Symptoms
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.
Detailed Description

During the escalation dose phase, patients will be unevenly randomized between groups, to end with a total of 60 patients, 12 at each dose, providing escalation is complete.

At the starting level, 8 patients will be administered either ACT017 at the lowest pharmacologically active dose of 125 mg (n=4) or the matching placebo (n=4).

After review by the DSMB of the first 24 hrs clinical data and the 24-hr CT scan, and where available MRI images, and providing the opinion is favorable (for criteria, see below, same section), the second cohort will be opened and consist of 8 new patients, 4 under the next active dose (250 mg), 2 at the initial starting dose (125 mg), and 2 under placebo.

Depending on next DSMB recommendation, under favorable conditions, the third cohort will be opened and patients will be randomized in receiving ACT017 verum 500 mg (n=4), versus 250 mg (n=2), 125 mg (n=2) and placebo (n=2), making it a cohort of 10 patients.

Similarly, still under favorable opinion from DSMB, the fourth cohort will randomize 12 new patients between 1000 mg (n=4), 500 mg (n=2), 250 mg (n=2), 125 mg (n=2), or placebo (n=2).

Once this cohort is administered, the DSMB will provide yet another opinion and, if positive, a fifth cohort of 22 patients will be randomized between 1000 mg (n=8), versus 500 mg (n=6), 250 mg (n=4), 125 mg (n=2), or placebo (n=2).

This proposed scheme is based on the absence of stopping signal either in dose escalation, or in the consolidation phase. It will require a rigorous process to ensure that randomization scheme is strictly adhered to, being a multicenter study, so that numbers are precisely those expected for each cohort and thus avoid undue consents and screen failures.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Acute Ischemic Stroke
Intervention  ICMJE
  • Drug: Intravenous ACT017 125 mg
    Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms
    Other Name: Thrombolysis by rtPA +/- thrombectomy
  • Drug: Intravenous ACT017 250 mg
    Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms
    Other Name: Thrombolysis by rtPA +/- thrombectomy
  • Drug: Intravenous ACT017 500 mg
    Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms
    Other Name: Thrombolysis by rtPA +/- thrombectomy
  • Drug: Intravenous 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
  • Other: 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
Study Arms  ICMJE
  • Experimental: Intravenous ACT017 125 mg
    Intravenous ACT017 125 mg to be added to a tissue plasminogen activator +/- mechanical thrombectomy
    Interventions:
    • Drug: Intravenous ACT017 125 mg
    • Drug: Intravenous ACT017 250 mg
    • Drug: Intravenous ACT017 500 mg
    • Drug: Intravenous ACT017 1000 mg
    • Other: Intravenous Placebo
  • Experimental: Intravenous ACT017 250 mg
    Intravenous ACT017 250 mg to be added to a tissue plasminogen activator +/- mechanical thrombectomy
    Interventions:
    • Drug: Intravenous ACT017 250 mg
    • Drug: Intravenous ACT017 500 mg
    • Drug: Intravenous ACT017 1000 mg
    • Other: Intravenous Placebo
  • Experimental: Intravenous ACT017 500 mg
    Intravenous ACT017 500 mg to be added to a tissue plasminogen activator +/- mechanical thrombectomy
    Interventions:
    • Drug: Intravenous ACT017 500 mg
    • Drug: Intravenous ACT017 1000 mg
    • Other: Intravenous Placebo
  • Experimental: Intravenous ACT017 1000 mg
    Intravenous ACT017 1000 mg to be added to a tissue plasminogen activator +/- mechanical thrombectomy
    Interventions:
    • Drug: Intravenous ACT017 1000 mg
    • Other: Intravenous Placebo
  • Placebo Comparator: Intravenous Placebo
    Intravenous Placebo to be added to a tissue plasminogen activator +/- mechanical thrombectomy
    Interventions:
    • Drug: Intravenous ACT017 125 mg
    • Drug: Intravenous ACT017 250 mg
    • Drug: Intravenous ACT017 500 mg
    • Drug: Intravenous ACT017 1000 mg
    • Other: Intravenous Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2019)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time of randomization);
  • Presenting with an acute ischemic stroke confirmed by imaging showing intra-cranial anterior circulation large vessel occlusion, including distal segments (M3), with a known time of onset, or when unknown the last time seen well that is inferior or as a maximum equal to 4.5 hrs when the diagnosis is ascertained and sufficient to allow the test treatment to be administered in this time-window;
  • Who are eligible to thrombolysis treatment with rtPA;
  • Who may undergo mechanical thrombectomy if eligible;

Exclusion Criteria:

  • Coma, and/or NIHSS >25;
  • Stroke of hemorrhagic origin;
  • Prior ischemic stroke within the past 3 months with mRS pre-stroke known to be ≥2;
  • Contra-indication to thrombolysis with rtPA:
  • Patients receiving anti-coagulants with the exception of heparin intake with a maximum dose of 50 IU/kg exclusively during the mechanical thrombectomy procedure;
  • Systolic blood pressure ≥185 mm Hg;
  • Diastolic blood pressure ≥110 mm Hg;
  • Glucose >200 mg/dL or <50 mg/dL;
  • Platelets <100 × 103/μL;
  • aPTT >39 s;
  • Prior hemorrhagic stroke.
  • Need for carotid stenting together with a dual anti-platelet treatment;
  • Concurrent anti-thrombotic treatment including anti-platelet agents, NSAIDs, and more generally with other medicines likely to interfere with hemostasis;
  • Hemorrhagic diathesis;
  • Known impaired renal function or serum creatinine >2X ULN (110 micromol/l or 1.2 mg/dl) at screening;
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andrea Comenducci, MD +33631003997 andrea.comenducci@acticor-biotech.com
Contact: Yannick Pletan, MD +33685946370 yannick.pletan@acticor-biotech.com
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03803007
Other Study ID Numbers  ICMJE ACT-CS-002
2018-002855-13 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Acticor Biotech
Study Sponsor  ICMJE Acticor Biotech
Collaborators  ICMJE
  • Orion Corporation, Orion Pharma
  • Axial Biotech, Inc
  • QPS
Investigators  ICMJE
Study Director: Andrea Comenducci, MD Acticor Biotech
PRS Account Acticor Biotech
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP