Glenzocimab in SARS-Cov-2 Acute Respiratory DistrEss syNdrome Related to COVID-19 (GARDEN)

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

A randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study to evaluate the efficacy and safety of glenzocimab in ARDS.

Study Overview

• Status: Completed
• Conditions: COVID-19; Acute Respiratory Distress Syndrome; ARDS; SARS-CoV Infection
• Intervention / Treatment: Drug: glenzocimab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67091
    • Hopital de Hautepierre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female hospitalized patients ≥ 18 years (i.e., at least 18 years old at the time of randomization), having given their written consent.
2. Having a positive RT-PCR test for COVID-19

3. 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

4. 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.

5. 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.
6. Women of child-bearing potential must have negative results of a urinary or plasma pregnancy test (serum HCG).

Exclusion Criteria:

1. Patients requiring immediate admission to the ICU,
2. Patients requiring invasive mechanical ventilation,
3. ARDS of another origin,
4. Concomitant pulmonary infection (pneumoniae) with another agent, notably bacterial or fungal,
5. Patients under immunosuppressive agents,
6. Childbirth within <10 days,
7. Pregnancy or breastfeeding,
8. Prior cardiopulmonary resuscitation <10 days,
9. Allergy or hypersensitivity to drugs of the same class
10. Participation in another interventional clinical trial within 30 days prior to the inclusion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; IV administration
Experimental: glenzocimab 1000 mg	Drug: glenzocimab; IV administration as a sterile product; Other Names: ACT017

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality at day 40		Day 40 (maximum)
WHO-COVID-19 Scale	WHO COVID-19 Ordinal Scoring Scale is 9 point ordinal scale	Up to Day 40
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.	Up to Day 40
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.	Up to Day 40
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.	Up to Day 40
SpO2 status	SpO2 status defined as: o Normal:>95%; Mild:93%<SpO2≤95%,; Moderate:90%<SpO2≤93%, o Severe:≤90%,; Death.	Up to Day 40
CHEST CT-Scan (or in exceptional cases, chest radiogram)		Day 4
Oxygen-free days		Up to Day 40
Admission to the ICU		Up to Day 40
ICU-free days		Up to Day 40
Hospital-free days		Up to Day 40
Clinical recovery and Time to Clinical recovery		Up to Day 40
Cure and Time-to-cure		Up to Day 40
Incidence, nature and severity of Adverse Events, SAEs, SUSARs and Treatment-Emergent Adverse Events (TEAEs)		Up to Day 40
Incidence of bleeding-related events		Up to Day 40
Incidence of hypersensitivity reactions		Up to Day 40
Changes from baseline on blood pressure		Up to Day 40
Changes from baseline on heart rate		Up to Day 40
Changes from baseline on NFS		Up to Day 40
Changes from baseline on INR/PTT		Up to Day 40
Changes from baseline on platelet count		Up to Day 40
Changes from baseline on plasma fibrinogen level		Up to Day 40
Changes from baseline on plasma D-Dimers level		Up to Day 40
Changes from baseline on serum-glucose level		Up to Day 40
Changes from baseline on urea level		Up to Day 40
Changes from baseline on creatinemia		Up to Day 40
Changes from baseline on LFTs (ASAT/ALAT)		Up to Day 40
Changes from baseline on CRP level		Up to Day 40
Changes from baseline on LDH level		Up to Day 40
Changes from baseline on IL6 level		Up to Day 40
Changes from baseline on Tnt		Up to Day 40
Changes from baseline on NT proBNP		Up to Day 40
Changes from baseline on procalcitonin level		Up to Day 40
Changes from baseline on ferritin level		Up to Day 40
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.	Up to Day 40

Collaborators and Investigators

• Sponsor: Acticor Biotech

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): August 6, 2021
• Study Completion (Actual): August 6, 2021

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: ARDS; Acute Respiratory Distress Syndrome; Covid 19; SARS-Cov; glenzocimab; ACT017; glycoprotein VI; antiplatelet agent
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Anticoagulants; Glenzocimab
• Other Study ID Numbers: ACT-CS-006; 2020-002733-15 (EudraCT Number)

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