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

NCT ID: NCT04429334

Last Updated: 2023-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-23
• Study Completion Date: 2022-06-22

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.

Conditions

COVID19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

nangibotide

Continuous infusion of experimental agent for up to 120 hours

Group Type: EXPERIMENTAL

nangibotide

Intervention Type: DRUG

nangibotide 1.0 mg/kg/h

placebo

Continuous infusion of matched placebo for up to 120 hours

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

matching placebo

Interventions

nangibotide

nangibotide 1.0 mg/kg/h

Intervention Type: DRUG

placebo

matching placebo

Intervention Type: DRUG

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

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inotrem

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Jacques Garaud, MD

Role: STUDY_CHAIR

INOTREM SA

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

Béthune, , 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

Trévenans, , France

Countries

Belgium; France

References

Francois B, Lambden S, Garaud JJ, Derive M, Grouin JM, Asfar P, Darreau C, Mira JP, Quenot JP, Lemarie J, Mercier E, Lacherade JC, Vinsonneau C, Fivez T, Helms J, Badie J, Levy M, Cuvier V, Salcedo-Magguilli M, Laszlo-Pouvreau AL, Laterre PF, Gibot S; ESSENTIAL investigators. Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial. EClinicalMedicine. 2023 Jun;60:102013. doi: 10.1016/j.eclinm.2023.102013. Epub 2023 May 31.

Reference Type: DERIVED

PMID: 37350989 (View on PubMed)

Other Identifiers

MOT-C-204

Identifier Type: -

Identifier Source: org_study_id