COVID19Phase 2ESSENTIALNCT04429334
Efficacy and Safety Study of Nangibotide in Patients With COVID-19 Receiving Ventilatory Support
A Phase 2 study testing nangibotide in people with COVID19, run by Inotrem at 17 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- COVID19
- What is being tested?
- nangibotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 17 sitesin 2 countries
- Study dates
- 23 Sep 2020to 22 Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provided informed consent (emergency consent according to local regulations where approved)
- Age 18 to 75 years (inclusive)
- Admitted to an intensive care unit
- 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
- A PaO2:FiO2 ratio of <200mmHg (<26.7kPa) with a FiO2 ≥0.6
- Confirmed laboratory diagnosis of COVID-19 within 7 days of meeting screening criteria
Who cannot join
- Known pregnancy (positive urine or serum pregnancy test)
- Ongoing treatment with an immunomodulatory agent not included in the standard of care for COVID-19 (including participation in clinical trials of such agents)".
- Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
- Anticipated transfer to another hospital, which is not a study site within 72 hours
- Expected to die within 6 months of treatment due to underlying chronic disease
- Limitations of care in place during current hospital admission
- -
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
France15 sites
CHU Angers
Angers, 49933
Centre hospitalier Victor Dupouy
Argenteuil, 95107
Centre Hospitalier Germont et Gauthier
Béthune, 62400
CHU Dijon - Bourgogne - Hôpital François Mitterrand
Dijon, 21079
CHD Site la Roche sur Yon, les Oudairies
La Roche-sur-Yon, 85 925
Centre hospitalier le Manas
Le Mans, 72037
Centre Hospitalier Universitaire Dupuytren
Limoges, 87042
Centre hospitalier de Melun
Melun, 77000
Hôpital Saint Eloi CHU Montpellier
Montpellier, 34295
Réanimation Médicale, Hôpital Central
Nancy, 54000
Hôpital Dieu - CHU Nanates
Nantes, 44093
Hôpital Cochin
Paris, 75014
Hôpital Civil - Nouvel Hôpital civil
Strasbourg, 67091
CHRU - Hôpital Bretonneau
Tours, 37044
Hôpital Franch-Comté Site Trevenans
Trévenans, 90400
Belgium2 sites
Clinique universitaire Saint-Luc
Brussels, B-1200
Ziekenhuis Oost-Limburg
Genk, 3600
About this study
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
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.
Read the 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
- Being tested
- nangibotide, placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nangibotideDrug
nangibotide 1.0 mg/kg/h
placeboDrug
matching placebo
| Study group | Role | What they receive |
|---|---|---|
| nangibotide | Experimental | Continuous infusion of experimental agent for up to 120 hours Receives: Drug: nangibotide |
| placebo | Placebo comparator | Continuous infusion of matched placebo for up to 120 hours Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events until day 28
Part 1
Measured: 28 days
Clinical Status (7-point Ordinal Scale) assessed at Day 28
Part 2
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2020
- Study start23 Sep 2020
- Primary completion20 May 2022
- Study completion22 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inotrem
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jean-Jacques Garaud, MD, Study chair, INOTREM SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04429334
- Sponsor's protocol ID
- MOT-C-204
- Acronym
- ESSENTIAL
- Status last verified
- May 2023
- First submitted
- 29 May 2020
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37350989
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04429334
- Acronym / sponsor ID
- ESSENTIAL / MOT-C-204
- Conditions
- COVID19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- InotremIndustry (pharma, biotech, devices)
- Study start
- 23 Sep 2020 (actual)
- Primary completion
- 20 May 2022 (actual)
- Study completion
- 22 Jun 2022 (actual)
- First posted
- 12 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nangibotide | Experimental | Drug: nangibotideContinuous infusion of experimental agent for up to 120 hours |
| placebo | Placebo comparator | Drug: placeboContinuous infusion of matched placebo for up to 120 hours |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provided informed consent (emergency consent according to local regulations where approved)
- Age 18 to 75 years (inclusive)
- Admitted to an intensive care unit
- 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
- A PaO2:FiO2 ratio of <200mmHg (<26.7kPa) with a FiO2 ≥0.6
Key exclusion criteria (7 listed)
- Known pregnancy (positive urine or serum pregnancy test)
- Ongoing treatment with an immunomodulatory agent not included in the standard of care for COVID-19 (including participation in clinical trials of such agents)".
- Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
- Anticipated transfer to another hospital, which is not a study site within 72 hours
- Expected to die within 6 months of treatment due to underlying chronic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nangibotidenangibotide 1.0 mg/kg/h | Drug | nangibotide |
| placebomatching placebo | Drug | placebo |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Derived from this study: PubMed 37350989Francois 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Jacques Garaud, MD study chair
INOTREM SA
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nangibotide in people with COVID19, run by Inotrem at 17 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events until day 28 (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04429334, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.