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

NCT ID: NCT04055909

Last Updated: 2023-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

355 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-13

Study Completion Date

2023-05-09

Brief Summary

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

Detailed Description

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All patients with a diagnosis of septic shock will be considered for study participation. All potential study patients will receive standard of care for the treatment of septic shock.

After screening for eligibility, patients meeting all inclusion and no exclusion criterion will be randomized. Patients will be randomized to one of three treatment arms.

Treatment with study drug must be initiated as early as possible, but no later than 24 hours after the onset of septic shock, defined by the start of vasopressor therapy.

Patients will be treated for at least 3 days with study drug. After the first 3 days of treatment, patients still requiring vasopressor will be treated until 24 hours after vasopressor withdrawal with a maximum treatment duration of 5 days.

Patients will be assessed at the End of Study (EoS) visit at day 28. After the last patient's day 28 visit, the study will be analyzed. Additional follow up (FU) visits will be conducted after 90 days, 6 and 12 months.

The objective of the study ist to compare the safety, tolerability and efficacy of two doses of nangibotide versus placebo, when given in addition to standard of care.

Conditions

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Shock, Septic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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nangibotide 1

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

Group Type EXPERIMENTAL

nangibotide low dose

Intervention Type DRUG

nangibotide 0.3 mg/kg/h

nangibotide 2

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

Group Type EXPERIMENTAL

nangibotide high dose

Intervention Type DRUG

nangibotide 1.0 mg/kg/h

Placebo

Treatment with a matched placebo infusion

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo

Interventions

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nangibotide low dose

nangibotide 0.3 mg/kg/h

Intervention Type DRUG

nangibotide high dose

nangibotide 1.0 mg/kg/h

Intervention Type DRUG

placebo

matching placebo

Intervention Type DRUG

Other Intervention Names

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LR12 LR12 matched placebo

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Previous episode of septic shock requiring vasopressor administration within current hospital stay
2. Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids \>75 mg prednisone daily or equivalent for more than 7 days
3. Immunosuppressive therapy related to recent (\<6 months) transplantation
4. Cancer chemotherapy (\<3 months) implying an immunodepression
5. Known HIV infection with low CD4 cell count (\<200) for at least 6 months
6. Known pregnancy (positive urine or serum pregnancy test)
7. Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
8. Ongoing documented or suspected endocarditis, history of prosthetic heart valves
9. Prolonged QT syndrome
10. End-stage neurological disease
11. End-stage cirrhosis (Child Pugh Class C)
12. Acute Physiology and Chronic Health Evaluation (APACHE II) score \<15 or ≥ 34
13. Home oxygen therapy on a regular basis for \> 6 h/day
14. Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)
15. Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
16. Moribund patients
17. Decision to limit full care taken before obtaining informed consent
18. Participation in another interventional study in the 3 months prior to randomization
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Inotrem

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Jacques Garaud, MD

Role: STUDY_DIRECTOR

CEO and Medical Officer

Locations

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Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Ziekenhuis Oost-Limburg

Genk, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

Centre hospitalier Jolimont-Lobbes

La Louvière, , Belgium

Site Status

CHU Marie Curie

Lodelinsart, , Belgium

Site Status

Clinique Saint-Pierre

Ottignies, , Belgium

Site Status

CHU UCL Namur asbl

Yvoir, , Belgium

Site Status

Nordsjællandshospital Hillerød

Hillerød, , Denmark

Site Status

Helsinki University Hospital Adult ICU PPDS

Helsinki, , Finland

Site Status

Kuopion Yliopistollinen sairaala

Kuopio, , Finland

Site Status

Tampereen yliopistollinen sairaala

Tampere, , Finland

Site Status

CHU Angers

Angers, , France

Site Status

Centre hospitalier Victor Dupouy

Argenteuil, , France

Site Status

Centre hospitalier de Béthune

Béthune, , France

Site Status

Hôpital Fleyriat

Bourg-en-Bresse, , France

Site Status

CHU Dijon - Hôpital François Mitterrand

Dijon, , France

Site Status

CHD les Oudairies

La Roche-sur-Yon, , France

Site Status

Hôpital de Bicêtre

Le Kremlin-Bicêtre, , France

Site Status

CHU LE Mans

Le Mans, , France

Site Status

CHRU Lille - Hôpital Roger Salengro

Lille, , France

Site Status

Hôpital Universitaire Dupuytren

Limoges, , France

Site Status

Centre Hospitalier Lyon Sud

Lyon, , France

Site Status

Hôpital Nord

Marseille, , France

Site Status

Centre hospitalier de Melun

Melun, , France

Site Status

CHRU Nancy - Hôpital Central

Nancy, , France

Site Status

Hôtel Dieu - Nanates

Nantes, , France

Site Status

CHU de Nîmes

Nîmes, , France

Site Status

Hôpital de la source

Orléans, , France

Site Status

Hôpital Lariboisière

Paris, , France

Site Status

Hôpital Saint Louis

Paris, , France

Site Status

Groupe hospitalier Pitié-Salpêtrière

Paris, , France

Site Status

Hôpital Cochin

Paris, , France

Site Status

CHRU Hôpital Bretonneau

Tours, , France

Site Status

Hôpital d'instruction des Armées Robert Picqué

Villenave-d'Ornon, , France

Site Status

St Jame's Hospital

Dublin, , Ireland

Site Status

Galway University Hospital

Galway, , Ireland

Site Status

Hospital del mar

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebrón

Barcelona, , Spain

Site Status

Hospital Clinical San Carlos

Madrid, , Spain

Site Status

Hospital Universitario Dentral de Asturias

Oviedo, , Spain

Site Status

Hospital Universitari Mutua de Terrassa

Terrassa, , Spain

Site Status

Hospital universitario DR. Peset Aleixandre

Valencia, , Spain

Site Status

Hospital Universitario y Politecnico la Fe

Valencia, , Spain

Site Status

Countries

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Belgium Denmark Finland France Ireland Spain

References

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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.

Reference Type DERIVED
PMID: 37269870 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34233965 (View on PubMed)

Other Identifiers

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2018-004827-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOT-C-203

Identifier Type: -

Identifier Source: org_study_id

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