Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock

NCT04055909 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MOT-C-2032018-004827-36
• Study Type: interventional
• Target: 355
• Locations: 6 countries
• Sites: 43

Brief Summary

This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.

Conditions

Shock, Septic

Keywords

Septic Shock

Outcome Measures

Primary Outcomes (1)

• Sequential organ failure assessment (SOFA) score

  Change of total SOFA score from baseline to day 5 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population)

  day 5

Secondary Outcomes (14)

• All-cause mortality

  day 5 and day 28

• Duration of ICU stay

  day 28

• Organe support free survival

  day 28

• Sepsis support index (SSI)

  day 28

• Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores

  day 1, day 2, day 3, day 4, day 5, day 6 and day 7

Study Arms (3)

nangibotide 1

EXPERIMENTAL

Treatment with study drug at at dose of 0.3mg/kg/hr

Drug: nangibotide low dose

nangibotide 2

EXPERIMENTAL

Treatment with study drug at at dose of 1.0mg/kg/hr

Drug: nangibotide high dose

Placebo

PLACEBO COMPARATOR

Treatment with a matched placebo infusion

Drug: placebo

Interventions

nangibotide low dose DRUG

nangibotide 0.3 mg/kg/h

Also known as: LR12

nangibotide 1

nangibotide high dose DRUG

nangibotide 1.0 mg/kg/h

Also known as: LR12

nangibotide 2

placebo DRUG

matching placebo

Also known as: matched placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent
• Age 18 to 85 years (inclusive)
• Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (≥65 years)
• Organ dysfunction defined as acute change in total SOFA score ≥ 2 points
• Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation
• Hyperlactatemia (blood lactate \>2 mmol/L or 18 mg/dL).

You may not qualify if:

• Previous episode of septic shock requiring vasopressor administration within current hospital stay
• Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids \>75 mg prednisone daily or equivalent for more than 7 days
• Immunosuppressive therapy related to recent (\<6 months) transplantation
• Cancer chemotherapy (\<3 months) implying an immunodepression
• Known HIV infection with low CD4 cell count (\<200) for at least 6 months
• Known pregnancy (positive urine or serum pregnancy test)
• Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
• Ongoing documented or suspected endocarditis, history of prosthetic heart valves
• Prolonged QT syndrome
• End-stage neurological disease
• End-stage cirrhosis (Child Pugh Class C)
• Acute Physiology and Chronic Health Evaluation (APACHE II) score \<15 or ≥ 34
• Home oxygen therapy on a regular basis for \> 6 h/day
• Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)
• Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg

Sponsors & Collaborators

• Inotrem: lead

Study Sites (43)

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Ziekenhuis Oost-Limburg

Genk, 3600, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Centre hospitalier Jolimont-Lobbes

La Louvière, 7100, Belgium

Location

CHU Marie Curie

Lodelinsart, 6042, Belgium

Location

Clinique Saint-Pierre

Ottignies, 1340, Belgium

Location

CHU UCL Namur asbl

Yvoir, 5530, Belgium

Location

Nordsjællandshospital Hillerød

Hillerød, DK-3400, Denmark

Location

Helsinki University Hospital Adult ICU PPDS

Helsinki, PL 340, Finland

Location

Kuopion Yliopistollinen sairaala

Kuopio, PO BOX 1777, Finland

Location

Tampereen yliopistollinen sairaala

Tampere, PL 2000, Finland

Location

CHU Angers

Angers, 49933, France

Location

Centre hospitalier Victor Dupouy

Argenteuil, 95100, France

Location

Centre hospitalier de Béthune

Béthune, 62408, France

Location

Hôpital Fleyriat

Bourg-en-Bresse, 01000, France

Location

CHU Dijon - Hôpital François Mitterrand

Dijon, 21079, France

Location

CHD les Oudairies

La Roche-sur-Yon, 85925, France

Location

Hôpital de Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

CHU LE Mans

Le Mans, 72000, France

Location

CHRU Lille - Hôpital Roger Salengro

Lille, 59037, France

Location

Hôpital Universitaire Dupuytren

Limoges, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

Hôpital Nord

Marseille, 13015, France

Location

Centre hospitalier de Melun

Melun, 77000, France

Location

CHRU Nancy - Hôpital Central

Nancy, 54035, France

Location

Hôtel Dieu - Nanates

Nantes, 44093, France

Location

CHU de Nîmes

Nîmes, 30029, France

Location

Hôpital de la source

Orléans, 45067, France

Location

Hôpital Lariboisière

Paris, 75010, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Groupe hospitalier Pitié-Salpêtrière

Paris, 75013, France

Location

Hôpital Cochin

Paris, 75014, France

Location

CHRU Hôpital Bretonneau

Tours, 37044, France

Location

Hôpital d'instruction des Armées Robert Picqué

Villenave-d'Ornon, 33882, France

Location

St Jame's Hospital

Dublin, Ireland

Location

Galway University Hospital

Galway, H91 YR71, Ireland

Location

Hospital del mar

Barcelona, 08003, Spain

Location

Hospital Universitario Vall d'Hebrón

Barcelona, Spain

Location

Hospital Clinical San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Dentral de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitari Mutua de Terrassa

Terrassa, 08221, Spain

Location

Hospital universitario DR. Peset Aleixandre

Valencia, 46017, Spain

Location

Hospital Universitario y Politecnico la Fe

Valencia, 46026, Spain

Location

Related Publications (2)

• Francois B, Lambden S, Fivez T, Gibot S, Derive M, Grouin JM, Salcedo-Magguilli M, Lemarie J, De Schryver N, Jalkanen V, Hicheur T, Garaud JJ, Cuvier V, Ferrer R, Bestle M, Pettila V, Mira JP, Bouisse C, Mercier E, Vermassen J, Huberlant V, Vinatier I, Anguel N, Levy M, Laterre PF; ASTONISH investigators. Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial. Lancet Respir Med. 2023 Oct;11(10):894-904. doi: 10.1016/S2213-2600(23)00158-3. Epub 2023 May 31.

  PMID: 37269870 DERIVED

• Francois B, Lambden S, Gibot S, Derive M, Olivier A, Cuvier V, Witte S, Grouin JM, Garaud JJ, Salcedo-Magguilli M, Levy M, Laterre PF. Rationale and protocol for the efficacy, safety and tolerability of nangibotide in patients with septic shock (ASTONISH) phase IIb randomised controlled trial. BMJ Open. 2021 Jul 7;11(7):e042921. doi: 10.1136/bmjopen-2020-042921.

  PMID: 34233965 DERIVED

MeSH Terms

Conditions

Shock, Septic

Interventions

nangibotide

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Jean-Jacques Garaud, MD

  CEO and Medical Officer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: August 14, 2019
• Study Start: November 13, 2019
• Primary Completion: May 9, 2022
• Study Completion: May 9, 2023
• Last Updated: April 11, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (23); ES (7); BE (7); FI (3); IE (2); DK (1)