Back to resultsGlenzocimab in SARS-Cov-2 Acute Respiratory DistrEss syNdrome Related to COVID-19 (GARDEN)
Primary Purpose
SARS-CoV Infection, Acute Respiratory Distress Syndrome, COVID-19
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
glenzocimab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for SARS-CoV Infection focused on measuring Covid 19, ARDS, SARS-Cov, glenzocimab, Acute Respiratory Distress Syndrome, ACT017, glycoprotein VI, antiplatelet agent
Eligibility Criteria
Inclusion Criteria:
- Male or female hospitalized patients ≥ 18 years (i.e., at least 18 years old at the time of randomization), having given their written consent.
- Having a positive RT-PCR test for COVID-19
Presenting with symptoms of COVID-19, including:
- Cough OR
- Shortness of breath or difficulty breathing OR at least 2 of the following
- Fever, defined as any body temperature 38°C
- Chills
- Repeated shaking with chills
- Muscle pain
- Headache
- Sore throat
- New loss of taste or smell
Presenting with signs of moderate but progressive pulmonary disease with:
- respiratory symptoms (cough, dyspnea, etc.),
- uni- or bilateral ground-glass opacities, or pulmonary infiltrates on chest radiograph and/or CT scan,
- clinical and biological evidence of progression over the past 48hrs.
Effective birth control that should have been in place for at least 2 months in non-menopausal women and 4 months for men after IMP administration. Birth control methods considered to be highly effective include:
- combined (estrogen-progestogen) hormonal contraception associated with the inhibition of ovulation: oral, intravaginal, transdermal,
- progesterone-only hormonal contraception associated with the inhibition of ovulation: oral, injectable, implantable,
- intrauterine device,
- intrauterine hormone-releasing system,
- bilateral tubal occlusion,
- vasectomized partner.
- Women of child-bearing potential must have negative results of a urinary or plasma pregnancy test (serum HCG).
Exclusion Criteria:
- Patients requiring immediate admission to the ICU,
- Patients requiring invasive mechanical ventilation,
- ARDS of another origin,
- Concomitant pulmonary infection (pneumoniae) with another agent, notably bacterial or fungal,
- Patients under immunosuppressive agents,
- Childbirth within <10 days,
- Pregnancy or breastfeeding,
- Prior cardiopulmonary resuscitation <10 days,
- Allergy or hypersensitivity to drugs of the same class
- Participation in another interventional clinical trial within 30 days prior to the inclusion.
Sites / Locations
- Hôpital de Hautepierre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
glenzocimab 1000 mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Progression from moderate to severe respiratory distress assessed at Day 4
Progression from moderate to severe assessed at Day 4 is a composite failure endpoint defined as the occurrence of at least one of the following failure events :
Respiratory rate (RR) ≥ 30/min, or
Oxygen Saturation (SpO2) ≤ 93% in resting state, or
Oxygen Pressure/ Inspired fraction (PaO2/FiO2) ≤ 200mmHg
Death occurring prior to or on Day 4
Secondary Outcome Measures
All cause mortality at day 40
WHO-COVID-19 Scale
WHO COVID-19 Ordinal Scoring Scale is 9 point ordinal scale
NEWS-2 Scale
Determines the degree of illness of a patient and prompts critical care intervention (recommended by NHS over original NEWS): total possible score ranges from 0 to 20. The higher the scores the greater the clinical risk.
Respiratory Rate status (RR)
Respiratory Rate status defined as:: o Normal:<20/min,
Mild:20/min≤RR<24/min,
Moderate:24/min≤RR<30/min, o Severe:≥30/min,
Death.
Hypoxemia status
Hypoxemia status defined as:: o Normal:>300mmHg,
Mild: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg,
Moderate:100mmHg<PaO2/FIO2≤200mmHg, o Severe:PaO2/FIO2≤100mmHg,
Death.
SpO2 status
SpO2 status defined as: o Normal:>95%
Mild:93%<SpO2≤95%,
Moderate:90%<SpO2≤93%, o Severe:≤90%,
Death.
CHEST CT-Scan (or in exceptional cases, chest radiogram)
Oxygen-free days
Admission to the ICU
ICU-free days
Hospital-free days
Clinical recovery and Time to Clinical recovery
Cure and Time-to-cure
Incidence, nature and severity of Adverse Events, SAEs, SUSARs and Treatment-Emergent Adverse Events (TEAEs)
Incidence of bleeding-related events
Incidence of hypersensitivity reactions
Changes from baseline on blood pressure
Changes from baseline on heart rate
Changes from baseline on NFS
Changes from baseline on INR/PTT
Changes from baseline on platelet count
Changes from baseline on plasma fibrinogen level
Changes from baseline on plasma D-Dimers level
Changes from baseline on serum-glucose level
Changes from baseline on urea level
Changes from baseline on creatinemia
Changes from baseline on LFTs (ASAT/ALAT)
Changes from baseline on CRP level
Changes from baseline on LDH level
Changes from baseline on IL6 level
Changes from baseline on Tnt
Changes from baseline on NT proBNP
Changes from baseline on procalcitonin level
Changes from baseline on ferritin level
ECG over the course of the study versus screening
Changes in one or several of the usual ECG parameters compared to baseline or screening, i.e. sinusal rhythm, cardiac axis, QRS value, QT/QTc segment, Wave direction, and any abnormality.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04659109
Brief Title
Glenzocimab in SARS-Cov-2 Acute Respiratory DistrEss syNdrome Related to COVID-19
Acronym
GARDEN
Official Title
A Randomized, Double Blind, Multicenter, Placebo Controlled, Parallel Group, Exploratory Efficacy and Safety Study of Glenzocimab in SARS-Cov-2-related Acute Respiratory Distress Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
December 16, 2020 (Actual)
Primary Completion Date
August 6, 2021 (Actual)
Study Completion Date
August 6, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acticor Biotech
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study to evaluate the efficacy and safety of glenzocimab in ARDS.
Detailed Description
This randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study evaluates the efficacy and safety of glenzocimab in ARDS.
Patients will be screened for eligibility and all tests should have results prior to any randomization, so as to avoid screening failures to a maximum extent. The turn-around time for these tests should be comprised within 24hrs to allow for rapid inclusions if needed. Eligible patients (n=68) will be randomized in a 1:1 ratio to glenzocimab or placebo. Patient inclusions will be fractioned into sequential (3-day apart) cohorts of growing size (2, 4 then 6 patients), each balanced between glenzocimab and placebo in order to check safety in a gradual manner. A Data Safety Monitoring Board (DSMB) will meet after 12 patients will have been accrued, and again after the first 30 patients.
Glenzocimab will be administered by IV infusion. The dosing regimen will be 1000mg for 3 days. All patients will receive in parallel the best medical care at the discretion of the investigating center, or per local guidelines. The allocation of each patient in any given center to an active treatment or placebo will strictly follow a central randomization scheme. The study period will be of a maximum of 40 days per patient. Patients will be closely monitored during the first 7 days following randomization with complete evaluations being performed at 24 hrs, 48 hrs, 72 hrs, then on Days 4 (96 hrs), 5 (120 hrs), 7 (+/-1 day), 14 (+/-2 days), 20 (+/-2 days), 40 (+/-3 days). Should a patient being discharged before Day 40, distant consultations by telemedicine may be undertaken if it is not deemed desirable that the patient comes back to the institution.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV Infection, Acute Respiratory Distress Syndrome, COVID-19, ARDS
Keywords
Covid 19, ARDS, SARS-Cov, glenzocimab, Acute Respiratory Distress Syndrome, ACT017, glycoprotein VI, antiplatelet agent
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study. The study evaluates the efficacy and safety of glenzocimab.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
glenzocimab 1000 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
glenzocimab
Other Intervention Name(s)
ACT017
Intervention Description
IV administration as a sterile product
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
IV administration
Primary Outcome Measure Information:
Title
Progression from moderate to severe respiratory distress assessed at Day 4
Description
Progression from moderate to severe assessed at Day 4 is a composite failure endpoint defined as the occurrence of at least one of the following failure events :
Respiratory rate (RR) ≥ 30/min, or
Oxygen Saturation (SpO2) ≤ 93% in resting state, or
Oxygen Pressure/ Inspired fraction (PaO2/FiO2) ≤ 200mmHg
Death occurring prior to or on Day 4
Time Frame
Day 4
Secondary Outcome Measure Information:
Title
All cause mortality at day 40
Time Frame
Day 40 (maximum)
Title
WHO-COVID-19 Scale
Description
WHO COVID-19 Ordinal Scoring Scale is 9 point ordinal scale
Time Frame
Up to Day 40
Title
NEWS-2 Scale
Description
Determines the degree of illness of a patient and prompts critical care intervention (recommended by NHS over original NEWS): total possible score ranges from 0 to 20. The higher the scores the greater the clinical risk.
Time Frame
Up to Day 40
Title
Respiratory Rate status (RR)
Description
Respiratory Rate status defined as:: o Normal:<20/min,
Mild:20/min≤RR<24/min,
Moderate:24/min≤RR<30/min, o Severe:≥30/min,
Death.
Time Frame
Up to Day 40
Title
Hypoxemia status
Description
Hypoxemia status defined as:: o Normal:>300mmHg,
Mild: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg,
Moderate:100mmHg<PaO2/FIO2≤200mmHg, o Severe:PaO2/FIO2≤100mmHg,
Death.
Time Frame
Up to Day 40
Title
SpO2 status
Description
SpO2 status defined as: o Normal:>95%
Mild:93%<SpO2≤95%,
Moderate:90%<SpO2≤93%, o Severe:≤90%,
Death.
Time Frame
Up to Day 40
Title
CHEST CT-Scan (or in exceptional cases, chest radiogram)
Time Frame
Day 4
Title
Oxygen-free days
Time Frame
Up to Day 40
Title
Admission to the ICU
Time Frame
Up to Day 40
Title
ICU-free days
Time Frame
Up to Day 40
Title
Hospital-free days
Time Frame
Up to Day 40
Title
Clinical recovery and Time to Clinical recovery
Time Frame
Up to Day 40
Title
Cure and Time-to-cure
Time Frame
Up to Day 40
Title
Incidence, nature and severity of Adverse Events, SAEs, SUSARs and Treatment-Emergent Adverse Events (TEAEs)
Time Frame
Up to Day 40
Title
Incidence of bleeding-related events
Time Frame
Up to Day 40
Title
Incidence of hypersensitivity reactions
Time Frame
Up to Day 40
Title
Changes from baseline on blood pressure
Time Frame
Up to Day 40
Title
Changes from baseline on heart rate
Time Frame
Up to Day 40
Title
Changes from baseline on NFS
Time Frame
Up to Day 40
Title
Changes from baseline on INR/PTT
Time Frame
Up to Day 40
Title
Changes from baseline on platelet count
Time Frame
Up to Day 40
Title
Changes from baseline on plasma fibrinogen level
Time Frame
Up to Day 40
Title
Changes from baseline on plasma D-Dimers level
Time Frame
Up to Day 40
Title
Changes from baseline on serum-glucose level
Time Frame
Up to Day 40
Title
Changes from baseline on urea level
Time Frame
Up to Day 40
Title
Changes from baseline on creatinemia
Time Frame
Up to Day 40
Title
Changes from baseline on LFTs (ASAT/ALAT)
Time Frame
Up to Day 40
Title
Changes from baseline on CRP level
Time Frame
Up to Day 40
Title
Changes from baseline on LDH level
Time Frame
Up to Day 40
Title
Changes from baseline on IL6 level
Time Frame
Up to Day 40
Title
Changes from baseline on Tnt
Time Frame
Up to Day 40
Title
Changes from baseline on NT proBNP
Time Frame
Up to Day 40
Title
Changes from baseline on procalcitonin level
Time Frame
Up to Day 40
Title
Changes from baseline on ferritin level
Time Frame
Up to Day 40
Title
ECG over the course of the study versus screening
Description
Changes in one or several of the usual ECG parameters compared to baseline or screening, i.e. sinusal rhythm, cardiac axis, QRS value, QT/QTc segment, Wave direction, and any abnormality.
Time Frame
Up to Day 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female hospitalized patients ≥ 18 years (i.e., at least 18 years old at the time of randomization), having given their written consent.
Having a positive RT-PCR test for COVID-19
Presenting with symptoms of COVID-19, including:
Cough OR
Shortness of breath or difficulty breathing OR at least 2 of the following
Fever, defined as any body temperature 38°C
Chills
Repeated shaking with chills
Muscle pain
Headache
Sore throat
New loss of taste or smell
Presenting with signs of moderate but progressive pulmonary disease with:
respiratory symptoms (cough, dyspnea, etc.),
uni- or bilateral ground-glass opacities, or pulmonary infiltrates on chest radiograph and/or CT scan,
clinical and biological evidence of progression over the past 48hrs.
Effective birth control that should have been in place for at least 2 months in non-menopausal women and 4 months for men after IMP administration. Birth control methods considered to be highly effective include:
combined (estrogen-progestogen) hormonal contraception associated with the inhibition of ovulation: oral, intravaginal, transdermal,
progesterone-only hormonal contraception associated with the inhibition of ovulation: oral, injectable, implantable,
intrauterine device,
intrauterine hormone-releasing system,
bilateral tubal occlusion,
vasectomized partner.
Women of child-bearing potential must have negative results of a urinary or plasma pregnancy test (serum HCG).
Exclusion Criteria:
Patients requiring immediate admission to the ICU,
Patients requiring invasive mechanical ventilation,
ARDS of another origin,
Concomitant pulmonary infection (pneumoniae) with another agent, notably bacterial or fungal,
Patients under immunosuppressive agents,
Childbirth within <10 days,
Pregnancy or breastfeeding,
Prior cardiopulmonary resuscitation <10 days,
Allergy or hypersensitivity to drugs of the same class
Participation in another interventional clinical trial within 30 days prior to the inclusion.
Facility Information:
Facility Name
Hôpital de Hautepierre
City
Strasbourg
ZIP/Postal Code
67091
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32500636
Citation
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.
Results Reference
background
PubMed Identifier
31017822
Citation
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.
Results Reference
background
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Glenzocimab in SARS-Cov-2 Acute Respiratory DistrEss syNdrome Related to COVID-19
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