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

Phase 2

Completed

• Conditions: SARS-CoV Infection; Acute Respiratory Distress Syndrome; COVID-19; ARDS
• Interventions: Drug: Placebo; Drug: glenzocimab

• Registration Number: NCT04659109
• Lead Sponsor: Acticor Biotech

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.

Study Timeline

• Study First Submitted: 2020-11-30
• Study First Submitted QC: 2020-12-07
• Study First Posted: 2020-12-09
• Study Start: 2020-12-16
• Primary Completion: 2021-08-06
• Study Completion: 2021-08-06
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-10
• Last Update Posted: 2021-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
glenzocimab 1000 mg	glenzocimab	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Changes from baseline on NFS	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 heart rate	Up to Day 40
Changes from baseline on procalcitonin level	Up to Day 40
Changes from baseline on ferritin level	Up to Day 40
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 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
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
Changes from baseline on urea level	Up to Day 40
Changes from baseline on creatinemia	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.

Trial Locations

Locations (1)

Hôpital de Hautepierre; 🇫🇷 Strasbourg, France