Clinical trial NCT04429334: Efficacy and Safety Study of Nangibotide in Patients With COVID-19 Receiving Ventilatory Support
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID19
Lead sponsor: Inotrem
Sponsor class: INDUSTRY
First posted: 2020-06-12
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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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Primary outcomes:
measure: Incidence of adverse events until day 28
timeFrame: 28 days
measure: Clinical Status (7-point Ordinal Scale) assessed at Day 28
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Clinique universitaire Saint-Luc
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Angers
country: France
facility: CHU Angers
city: Argenteuil
country: France
facility: Centre hospitalier Victor Dupouy
city: Bethune
country: France
facility: Centre Hospitalier Germont et Gauthier
city: Dijon
country: France
facility: CHU Dijon - Bourgogne - Hôpital François Mitterrand
city: La Roche sur Yon
country: France
facility: CHD Site la Roche sur Yon, les Oudairies
city: Le Mans
country: France
facility: Centre hospitalier le Manas
city: Limoges
country: France
facility: Centre Hospitalier Universitaire Dupuytren
city: Melun
country: France
facility: Centre hospitalier de Melun
city: Montpellier
country: France
facility: Hôpital Saint Eloi CHU Montpellier
city: Nancy
country: France
facility: Réanimation Médicale, Hôpital Central
city: Nantes
country: France
facility: Hôpital Dieu - CHU Nanates
city: Paris
country: France
facility: Hôpital Cochin
city: Strasbourg
country: France
facility: Hôpital Civil - Nouvel Hôpital civil
city: Tours
country: France
facility: CHRU - Hôpital Bretonneau
city: Trevenans
country: France
facility: Hôpital Franch-Comté Site Trevenans
Study officials:
affiliation: INOTREM SA
name: Jean-Jacques Garaud, MD
role: STUDY_CHAIR
References: