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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID19
• Intervention / Treatment: Drug: placebo; Drug: nangibotide

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.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jean-Jacques Garaud, MD; Phone Number: +33 (0)9 66 81 79 00; Email: covtrem@inotrem.com

Study Locations

• Belgium
  • Brussels, Belgium, B-1200
    • Clinique Universitaire Saint-Luc
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg
• France
  • Angers, France, 49933
    • CHU Angers
  • Argenteuil, France, 95107
    • Centre Hospitalier Victor Dupouy
  • Bethune, France, 62400
    • Centre Hospitalier Germont et Gauthier
  • Dijon, France, 21079
    • CHU Dijon - Bourgogne - Hôpital François Mitterrand
  • La Roche sur Yon, France, 85 925
    • CHD Site la Roche sur Yon, les Oudairies
  • Le Mans, France, 72037
    • Centre hospitalier le Manas
  • Limoges, France, 87042
    • Centre Hospitalier Universitaire Dupuytren
  • Melun, France, 77000
    • Centre Hospitalier de Melun
  • Montpellier, France, 34295
    • Hôpital saint Eloi CHU Montpellier
  • Nancy, France, 54000
    • Réanimation Médicale, Hôpital Central
  • Nantes, France, 44093
    • Hôpital Dieu - CHU Nanates
  • Paris, France, 75014
    • Hopital Cochin
  • Strasbourg, France, 67091
    • Hôpital Civil - Nouvel Hôpital civil
  • Tours, France, 37044
    • CHRU - Hôpital Bretonneau
  • Trevenans, France, 90400
    • Hôpital Franch-Comté Site Trevenans

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nangibotide; Continuous infusion of experimental agent for up to 120 hours	Drug: nangibotide; nangibotide 1.0 mg/kg/h
Placebo Comparator: placebo; Continuous infusion of matched placebo for up to 120 hours	Drug: placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events until day 28	Part 1	28 days
Clinical Status (7-point Ordinal Scale) assessed at Day 28	Part 2	28 days

Collaborators and Investigators

• Sponsor: Inotrem
• Investigators: Study Chair: Jean-Jacques Garaud, MD, INOTREM SA

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): May 20, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Inflammatory Agents; Nangibotide
• Other Study ID Numbers: MOT-C-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No