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

Sponsor

Acticor Biotech (Industry)

Overall Status

Completed

CT.gov ID

NCT04659109

Collaborator

(none)

Enrollment

Location

Arms

7.7

Actual Duration (Months)

7.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV Infection Acute Respiratory Distress Syndrome COVID-19 ARDS	Drug: glenzocimab Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.A randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study. The study evaluates the efficacy and safety of glenzocimab.

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 16, 2020

Actual Primary Completion Date :

Aug 6, 2021

Actual Study Completion Date :

Aug 6, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: glenzocimab 1000 mg

Drug: glenzocimab

IV administration as a sterile product

Other Names:

ACT017

Placebo Comparator: Placebo

Drug: Placebo

IV administration

Outcome Measures

Primary Outcome Measures

Progression from moderate to severe respiratory distress assessed at Day 4 [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 [Day 40 (maximum)]
WHO-COVID-19 Scale [Up to Day 40]
WHO COVID-19 Ordinal Scoring Scale is 9 point ordinal scale
NEWS-2 Scale [Up to Day 40]
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) [Up to Day 40]
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 [Up to Day 40]
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 [Up to Day 40]
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) [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 [Up to Day 40]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.