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.

François B, Lambden S, Garaud JJ, Derive M, Grouin JM, Asfar P, Darreau C, Mira JP, Quenot JP, Lemarié J, Mercier E, Lacherade JC and 10 more

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Vinsonneau C, Fivez T, Helms J, Badie J, Levy M, Cuvier V, Salcedo-Magguilli M, Laszlo-Pouvreau AL, Laterre PF, Gibot S

EClinicalMedicine31 May 2023Cited by 13 (Europe PMC)

PMID37350989PMCIDPMC10231876DOI10.1016/j.eclinm.2023.102013PepBankPUB-37350989

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Summary

BackgroundActivation of the TREM-1 pathway is associated with outcome in life threatening COVID-19. Data suggest that modulation of this pathway with nangibotide, a TREM-1 modulator may improve survival in TREM-1 activated patients (identified using the biomarker sTREM-1).MethodsPhase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0 mg/kg/h) compared to placebo. Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS. Patients were included from September 2020 to April 2022, with a pause in recruitment between January and August 2021. Primary outcome was the improvement in clinical status defined by a seven-point ordinal scale in the overall population with a planned sensitivity analysis in the subgroup of patients with a sTREM-1 level above the median value at baseline (high sTREM-1 group). Secondary endpoints included safety and all-cause 28-day and day 60 mortality. The study was registered in EudraCT (2020-001504-42) and ClinicalTrials.gov (NCT04429334).FindingsThe study was stopped after 220 patients had been recruited. Of them, 219 were included in the mITT analysis. Nangibotide therapy was associated with an improved clinical status at day 28. Fifty-two (52.0%) of patients had improved in the placebo group compared to 77 (64.7%) of the nangibotide treated population, an odds ratio (95% CI) for improvement of 1.79 (1.02-3.14), p = 0.043. In the high sTREM-1 population, 18 (32.7%) of placebo patients had improved by day 28 compared to 26 (48.1%) of treated patients, an odds ratio (95% CI) of 2.17 (0.96-4.90), p = 0.063 was observed. In the overall population, 28 (28.0%) of placebo treated patients were not alive at the day 28 visit compared to 19 (16.0%) of nangibotide treated patients, an absolute improvement (95% CI) in all-cause mortality at day 28, adjusted for baseline clinical status of 12.1% (1.18-23.05). In the high sTREM-1 population (n = 109), 23 (41.8%) of patients in the placebo group and 12 (22.2%) of patients in the nangibotide group were not alive at day 28, an adjusted absolute reduction in mortality of 19.9% (2.78-36.98). The rate of treatment emergent adverse events was similar in both placebo and nangibotide treated patients.InterpretationWhilst the study was stopped early due to low recruitment rate, the ESSENTIAL study demonstrated that TREM-1 modulation with nangibotide is safe in COVID-19, and results in a consistent pattern of improved clinical status and mortality compared to placebo. The relationship between sTREM-1 and both risk of death and treatment response merits further evaluation of nangibotide using precision medicine approaches in life threatening viral pneumonitis.FundingThe study was sponsored by Inotrem SA.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanRandomized controlled trialEfficacy outcome
In patients receiving respiratory support for COVID-19, clinical improvement occurred in 64.7% with nangibotide versus 52.0% with placebo.
In plain wordsIn patients receiving respiratory support for COVID-19, clinical improvement occurred in 64.7% with nangibotide versus 52.0% with placebo.
Peptide
Nangibotide
Outcome
IncreaseClinical improvement at day 28, overall
Study
n = 219
Comparator
Placebo
Analysis
Primary
Outcome group
Overall treatment effect · Respiratory
Studied dose
1.0 mg/kg/hAs given in this study (human).
Measurements
Patients with improved clinical status at day 28
64.7%
nangibotide
Patients with improved clinical status at day 28
52%
placebo
Odds ratio for clinical improvement
1.79 OR
nangibotide versus placebo
Odds ratio 95% CI
1.02 to 3.14 OR
nangibotide versus placebo
P value
0.043
clinical improvement
Source sentences
Summary
Fifty-two (52.0%) of patients had improved in the placebo group compared to 77 (64.7%) of the nangibotide treated population, an odds ratio (95% CI) for improvement of 1.79 (1.02-3.14), p = 0.043.
3 context sentences(design, population, supporting numbers)
Summary · context
Nangibotide therapy was associated with an improved clinical status at day 28.
Summary · context
Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0 mg/kg/h) compared to placebo.
Summary · context
Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS.
Show in the study text Report a problemFND-3735098901
02HumanRandomized controlled trialSafety outcome
In COVID-19 patients receiving respiratory support, day 28 mortality was 16.0% with nangibotide versus 28.0% with placebo.
In plain wordsIn COVID-19 patients receiving respiratory support, day 28 mortality was 16.0% with nangibotide versus 28.0% with placebo.
Peptide
Nangibotide
Outcome
DecreaseDay 28 mortality, overall
Study
n = 219
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
1.0 mg/kg/hAs given in this study (human).
Measurements
Deaths by day 28
19 patients
nangibotide
Mortality at day 28
16%
nangibotide
Deaths by day 28
28 patients
placebo
Mortality at day 28
28%
placebo
Adjusted absolute mortality improvement
12.1%
nangibotide versus placebo
Adjusted absolute mortality improvement 95% CI
1.18 to 23.05%
nangibotide versus placebo
Source sentences
Summary
In the overall population, 28 (28.0%) of placebo treated patients were not alive at the day 28 visit compared to 19 (16.0%) of nangibotide treated patients, an absolute improvement (95% CI) in all-cause mortality at day 28, adjusted for baseline clinical status of 12.1% (1.18-23.05).
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0 mg/kg/h) compared to placebo.
Summary · context
Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS.
Show in the study text Report a problemFND-3735098903
03HumanRandomized controlled trialSafety outcome
In COVID-19 patients receiving respiratory support, treatment-emergent adverse event rates were similar with nangibotide and placebo.
In plain wordsIn COVID-19 patients receiving respiratory support, adverse event rates were similar with nangibotide and placebo.
Peptide
Nangibotide
Outcome
No significant changeTreatment-emergent adverse events
Study
n = 219
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Studied dose
1.0 mg/kg/hAs given in this study (human).
Source sentences
Summary
The rate of treatment emergent adverse events was similar in both placebo and nangibotide treated patients.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0 mg/kg/h) compared to placebo.
Summary · context
Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS.
Show in the study text Report a problemFND-3735098905
04HumanRandomized controlled trialSafety outcome
In COVID-19 patients with high sTREM-1, day 28 mortality was 22.2% with nangibotide versus 41.8% with placebo.
In plain wordsIn COVID-19 patients with high sTREM-1, day 28 mortality was 22.2% with nangibotide versus 41.8% with placebo.
Peptide
Nangibotide
Outcome
DecreaseDay 28 mortality, high sTREM-1
Study
n = 109
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
1.0 mg/kg/hAs given in this study (human).
Measurements
Deaths by day 28
12 patients
nangibotide, high sTREM-1
Mortality at day 28
22.2%
nangibotide, high sTREM-1
Deaths by day 28
23 patients
placebo, high sTREM-1
Mortality at day 28
41.8%
placebo, high sTREM-1
Adjusted absolute mortality reduction
19.9%
high sTREM-1
Adjusted absolute mortality reduction 95% CI
2.78 to 36.98%
high sTREM-1
Source sentences
Summary
In the high sTREM-1 population (n = 109), 23 (41.8%) of patients in the placebo group and 12 (22.2%) of patients in the nangibotide group were not alive at day 28, an adjusted absolute reduction in mortality of 19.9% (2.78-36.98).
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0 mg/kg/h) compared to placebo.
Summary · context
Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS.
Show in the study text Report a problemFND-3735098904
05HumanRandomized controlled trialEfficacy outcome
In COVID-19 patients with high sTREM-1, day 28 clinical improvement was 48.1% with nangibotide versus 32.7% with placebo, without statistical significance.
In plain wordsIn COVID-19 patients with high sTREM-1, nangibotide did not significantly improve day 28 clinical status versus placebo.
Peptide
Nangibotide
Outcome
No significant changeClinical improvement at day 28, high sTREM-1
Study
n = 109
Comparator
Placebo
Outcome group
Overall treatment effect · Respiratory
Studied dose
1.0 mg/kg/hAs given in this study (human).
Measurements
Patients with improved clinical status at day 28
48.1%
nangibotide, high sTREM-1
Patients with improved clinical status at day 28
32.7%
placebo, high sTREM-1
Odds ratio for clinical improvement
2.17 OR
high sTREM-1
Odds ratio 95% CI
0.96 to 4.9 OR
high sTREM-1
P value
0.063
high sTREM-1
Source sentences
Summary
In the high sTREM-1 population, 18 (32.7%) of placebo patients had improved by day 28 compared to 26 (48.1%) of treated patients, an odds ratio (95% CI) of 2.17 (0.96-4.90), p = 0.063 was observed.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0 mg/kg/h) compared to placebo.
Summary · context
Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS.
Show in the study text Report a problemFND-3735098902

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Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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