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

• ClinicalTrials.gov Identifier: NCT04429334
• Recruitment Status: Completed
• First Posted: June 12, 2020
• Last Update Posted: May 3, 2023
• Sponsor: Inotrem
• Information provided by (Responsible Party): Inotrem

Tracking Information

• First Submitted Date: May 29, 2020
• First Posted Date: June 12, 2020
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: September 23, 2020
• Actual Primary Completion Date: May 20, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 3, 2023)

• Incidence of adverse events until day 28 [ Time Frame: 28 days ]
  Part 1
• Clinical Status (7-point Ordinal Scale) assessed at Day 28 [ Time Frame: 28 days ]
  Part 2

Original Primary Outcome Measures (submitted: June 11, 2020)

• Adverse Events [ Time Frame: 28 days ]
  Incidence of adverse events until day 28
• Mortality [ Time Frame: 28 days ]
  Incidence of mortality until day 28

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: COVID19

Intervention

• Drug: nangibotide
  nangibotide 1.0 mg/kg/h
• Drug: placebo
  matching placebo

Study Arms

• Experimental: nangibotide
  Continuous infusion of experimental agent for up to 120 hours
  Intervention: Drug: nangibotide
• Placebo Comparator: placebo
  Continuous infusion of matched placebo for up to 120 hours
  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 19, 2023): 220
• Original Estimated Enrollment (submitted: June 11, 2020): 60
• Actual Study Completion Date: June 22, 2022
• Actual Primary Completion Date: May 20, 2022 (Final data collection date for primary outcome measure)

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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Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France

Administrative Information

• NCT Number: NCT04429334
• Other Study ID Numbers: MOT-C-204
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Inotrem
• Original Responsible Party: Same as current
• Current Study Sponsor: Inotrem
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Jean-Jacques Garaud, MD; INOTREM SA

• PRS Account: Inotrem
• Verification Date: May 2023