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Efficacy and Safety Study of Nangibotide in Patients With COVID-19 Receiving Ventilatory Support

Phase 2
Completed
Conditions
COVID19
Interventions
Drug: placebo
Registration Number
NCT04429334
Lead Sponsor
Inotrem
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
220
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboplaceboContinuous infusion of matched placebo for up to 120 hours
nangibotidenangibotideContinuous infusion of experimental agent for up to 120 hours
Primary Outcome Measures
NameTimeMethod
Clinical Status (7-point Ordinal Scale) assessed at Day 2828 days

Part 2

Incidence of adverse events until day 2828 days

Part 1

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (17)

Clinique universitaire Saint-Luc

🇧🇪

Brussels, Belgium

Ziekenhuis Oost-Limburg

🇧🇪

Genk, Belgium

CHU Angers

🇫🇷

Angers, France

Centre hospitalier Victor Dupouy

🇫🇷

Argenteuil, France

CHU Dijon - Bourgogne - Hôpital François Mitterrand

🇫🇷

Dijon, France

Centre Hospitalier Germont et Gauthier

🇫🇷

Bethune, France

CHD Site la Roche sur Yon, les Oudairies

🇫🇷

La Roche sur Yon, France

Centre Hospitalier Universitaire Dupuytren

🇫🇷

Limoges, France

Hôpital Saint Eloi CHU Montpellier

🇫🇷

Montpellier, France

Centre hospitalier le Manas

🇫🇷

Le Mans, France

Centre hospitalier de Melun

🇫🇷

Melun, France

Hôpital Dieu - CHU Nanates

🇫🇷

Nantes, France

Réanimation Médicale, Hôpital Central

🇫🇷

Nancy, France

Hôpital Franch-Comté Site Trevenans

🇫🇷

Trevenans, France

Hôpital Civil - Nouvel Hôpital civil

🇫🇷

Strasbourg, France

CHRU - Hôpital Bretonneau

🇫🇷

Tours, France

Hôpital Cochin

🇫🇷

Paris, France

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