Clinical trial NCT04659109: Glenzocimab in SARS-Cov-2 Acute Respiratory DistrEss syNdrome Related to COVID-19
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Acticor Biotech
Sponsor class: INDUSTRY
First posted: 2020-12-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression from moderate to severe respiratory distress assessed at Day 4
timeFrame: Day 4
Secondary outcomes:
measure: All cause mortality at day 40
timeFrame: Day 40 (maximum)
measure: WHO-COVID-19 Scale
timeFrame: Up to Day 40
measure: NEWS-2 Scale
timeFrame: Up to Day 40
measure: Respiratory Rate status (RR)
timeFrame: Up to Day 40
measure: Hypoxemia status
timeFrame: Up to Day 40
measure: SpO2 status
timeFrame: Up to Day 40
measure: CHEST CT-Scan (or in exceptional cases, chest radiogram)
timeFrame: Day 4
measure: Oxygen-free days
timeFrame: Up to Day 40
measure: Admission to the ICU
timeFrame: Up to Day 40
measure: ICU-free days
timeFrame: Up to Day 40
measure: Hospital-free days
timeFrame: Up to Day 40
measure: Clinical recovery and Time to Clinical recovery
timeFrame: Up to Day 40
measure: Cure and Time-to-cure
timeFrame: Up to Day 40
measure: Incidence, nature and severity of Adverse Events, SAEs, SUSARs and Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 40
measure: Incidence of bleeding-related events
timeFrame: Up to Day 40
measure: Incidence of hypersensitivity reactions
timeFrame: Up to Day 40
measure: Changes from baseline on blood pressure
timeFrame: Up to Day 40
measure: Changes from baseline on heart rate
timeFrame: Up to Day 40
measure: Changes from baseline on NFS
timeFrame: Up to Day 40
measure: Changes from baseline on INR/PTT
timeFrame: Up to Day 40
measure: Changes from baseline on platelet count
timeFrame: Up to Day 40
measure: Changes from baseline on plasma fibrinogen level
timeFrame: Up to Day 40
measure: Changes from baseline on plasma D-Dimers level
timeFrame: Up to Day 40
measure: Changes from baseline on serum-glucose level
timeFrame: Up to Day 40
measure: Changes from baseline on urea level
timeFrame: Up to Day 40
measure: Changes from baseline on creatinemia
timeFrame: Up to Day 40
measure: Changes from baseline on LFTs (ASAT/ALAT)
timeFrame: Up to Day 40
measure: Changes from baseline on CRP level
timeFrame: Up to Day 40
measure: Changes from baseline on LDH level
timeFrame: Up to Day 40
measure: Changes from baseline on IL6 level
timeFrame: Up to Day 40
measure: Changes from baseline on Tnt
timeFrame: Up to Day 40
measure: Changes from baseline on NT proBNP
timeFrame: Up to Day 40
measure: Changes from baseline on procalcitonin level
timeFrame: Up to Day 40
measure: Changes from baseline on ferritin level
timeFrame: Up to Day 40
measure: ECG over the course of the study versus screening
timeFrame: Up to Day 40
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
Study officials:
References:
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.
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.