Official Title
Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients With ventiLatory Support (ESSENTIAL) A Randomized, Double-blind, Placebo-controlled Study With Adaptive Features
Brief Summary

This is a randomized, double-blind, placebo-controlled, in which one dose of nangibotide will be tested versus placebo. All patients with a diagnosis of COVID-19, and a requirement for respiratory support will be considered for study participation. The applicable local requirements for informed consent will be followed. Where permissible, an emergency consent procedure will be followed for patients unable to provide consent by themselves. All potential study patients will receive standard of care treatment throughout the study. Patients will receive a continuous intravenous (i.v.) infusion of nangibotide at 1.0 mg/kg/h or a matching placebo. Treatment with study drug must be initiated as early as possible but no later than 48 hours after the initiation of ventilatory support (Patients will be treated for 5 days or until discharge from critical care, whichever is sooner). Follow-up visits will be performed on days 8 and 14. The end of study visit is at day 28. A further follow up visit will be undertaken on day 60.

Detailed Description

ESSENTIAL was a randomized, double-blind, placebo-controlled trial, in which one dose of
nangibotide was tested versus placebo. It took place in 14 sites in France and Belgium. The
study was overseen by an independent Data Monitoring Committee (DMC).

The study was divided into two parts running sequentially without unblinding. Part 1
evaluated safety and tolerability study and included 60 patients, randomized in a 2:1 ratio
of nangibotide to placebo. Part 2 included all recruited patients with an initially planned
sample size of 370 patients, randomized in a 1:1 ratio of nangibotide to placebo.

All patients or their legally authorised representatives provided written informed consent
or, in relevant countries, an independent physician, confirmed patient eligibility for
enrolment in the trial.

Patients received a continuous intravenous infusion of nangibotide at 1.0 mg/kg/h or a
matching placebo for 5 days (or until discharge from ICU, whichever was sooner). The
treatment was in addition to standard of care.

Completed
COVID19

Drug: nangibotide

nangibotide 1.0 mg/kg/h

Drug: placebo

matching placebo

Eligibility Criteria

Inclusion Criteria:

1. Provided informed consent (emergency consent according to local regulations where
approved)

2. Age 18 to 75 years (inclusive)

3. Admitted to an intensive care unit

4. Treatment with High Flow Nasal Oxygen, non-invasive ventilation or invasive mechanical
ventilation for acute respiratory failure caused by COVID-19 for less than 48 hours

5. A PaO2:FiO2 ratio of <200mmHg (<26.7kPa) with a FiO2 ≥0.6

6. Confirmed laboratory diagnosis of COVID-19 within 7 days of meeting screening criteria

Exclusion Criteria:

1. Known pregnancy (positive urine or serum pregnancy test)

2. Ongoing treatment with an immunomodulatory agent not included in the standard of care
for COVID-19 (including participation in clinical trials of such agents)".

3. Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg

4. Anticipated transfer to another hospital, which is not a study site within 72 hours

5. Expected to die within 6 months of treatment due to underlying chronic disease

6. Limitations of care in place during current hospital admission

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Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 75 Years
Countries
Belgium
France
Locations

Clinique universitaire Saint-Luc
Brussels, Belgium

Ziekenhuis Oost-Limburg
Genk, Belgium

CHU Angers
Angers, France

Centre hospitalier Victor Dupouy
Argenteuil, France

Centre Hospitalier Germont et Gauthier
Bethune, France

CHU Dijon - Bourgogne - Hôpital François Mitterrand
Dijon, France

CHD Site la Roche sur Yon, les Oudairies
La Roche sur Yon, France

Centre hospitalier le Manas
Le Mans, France

Centre Hospitalier Universitaire Dupuytren
Limoges, France

Centre hospitalier de Melun
Melun, France

Hôpital Saint Eloi CHU Montpellier
Montpellier, France

Réanimation Médicale, Hôpital Central
Nancy, France

Hôpital Dieu - CHU Nanates
Nantes, France

Hôpital Cochin
Paris, France

Hôpital Civil - Nouvel Hôpital civil
Strasbourg, France

CHRU - Hôpital Bretonneau
Tours, France

Hôpital Franch-Comté Site Trevenans
Trevenans, France

Jean-Jacques Garaud, MD, Study Chair
INOTREM SA

NCT Number
MeSH Terms
COVID-19
Nangibotide