Clinical trial NCT04393038: ABX464 in Treating Inflammation and Preventing Acute Respiratory Failure in Patients With COVID-19
Official title: A Phase 2/3, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ABX464 in Treating Inflammation and Preventing COVID-19 Associated Acute Respiratory Failure in Patients Aged ≥ 65 and Patients Aged ≥18 With at Least One Additional Risk Factor Who Are Infected With SARS-CoV-2.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Keywords: COVID-19
ABX464
Lead sponsor: Abivax S.A.
Sponsor class: INDUSTRY
First posted: 2020-05-19
Enrollment: 509
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 2/3, randomized, double blind, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).

Detailed description: This phase 2/3 study will evaluate the efficacy and safety of ABX464 50mg QD (oral capsule), on treating inflammation and preventing acute respiratory failure in patients infected with SARS-CoV-2.

Eligible patients will be randomized according to a 2:1 ratio into 2 treatment cohorts as follows:

* Standard of Care + Placebo cohort: 344 patients
* Standard of Care + ABX464 50mg QD: 690 patients

Study design:

The study will consist of 2 periods:

* Treatment phase: randomized patients will be treated for 28 days
* Safety follow-up phase of 14 days after which the End of Study visit (EOS) will be performed.

Eligibility criteria: Inclusion Criteria:

1. Adult (≥ 18 years old) men or women, hospitalized or not hospitalized, diagnosed for SARS-CoV-2 infection by PCR, with at least one associated risk factor. Considered risk factors are:

   * Age ≥ 65 years
   * Obesity defined as BMI ≥ 30
   * Recent history of uncontrolled High Blood Pressure (SBP \> 150 mm Hg DBP \>100 mm Hg) according to investigator
   * Treated diabetes (type I or II)
   * History of ischemic cardiovascular disease
2. Symptomatic patients at enrollment. Symptoms are defined as fever (body temperature ≥ 37.8 C oral/tympanic, or ≥ 38.2 C rectal) for more than 24 hours associated either with headache, sore throat, dry cough, fatigue, chest pain or choking sensation (with no associated respiratory distress), myalgia, anosmia or ageusia.
3. Patients with pulse oximetry arterial saturation ≥ 92 % on room air at enrolment.
4. Patients with the following hematological and biochemical laboratory parameters obtained within 7 days prior to Day 0:

   * Hemoglobin above 9.0 g / dL
   * Absolute Neutrophil Count ≥ 1000 / mm3
   * Platelets ≥ 100 000 mm3;
   * Creatinine clearance ≥ 50 mL / min by the Cockcroft Gault formula
   * Total serum bilirubin \< 2 x ULN
   * Alkaline phosphatase \< 2 x ULN, AST (SGOT) and ALT (SGPT) \< 3 x ULN;

Exclusion Criteria:

1. Patients with moderate or severe acute respiratory failure or requiring noninvasive ventilation or oxygen or with SpO2 \< 92% or tachypnea (respiratory rate ≥ 30 breaths/min).
2. Patients treated with immunosuppressors and/or immunomodulators.
3. Engrafted patients (organ and/or hematopoietic stem cells).
4. Patients with uncontrolled auto-immune disease.
5. Patients with known or suspected active (i.e. not controlled) bacterial, viral (excluding COVID-19) or fungal infections.
6. Patients with preexisting, severe and not controlled organ failure.
7. History or active malignancy requiring chemotherapy or radiation therapy (excluding 2 years disease free survivor patients).
8. Pregnant or breast-feeding women.
9. Illicit drug or alcohol abuse or dependence that may compromise the patient's safety or adherence to the study protocol.
10. Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer.
11. Hypersensitivity to ABX464 and/or its excipients.
12. Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.

Primary outcomes:
measure: Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive
timeFrame: at the end of the 28-day treatment period
Secondary outcomes:
measure: Rate of patients hospitalized
timeFrame: 28-day treatment period
measure: Percentage of patients reporting each severity rating on a 7-point ordinal scale
timeFrame: 28-day treatment period
measure: Change from enrolment in inflammatory markers in plasma and in immune phenotype and assessment of cell-activation markers in PBMCs
timeFrame: at each study visit during the 28-day treatment period
measure: Rate of patients requiring oxygen supplementation
timeFrame: 28-day treatment period
measure: Time to hospitalization
timeFrame: 28-day treatment period
measure: Time to assisted ventilation and oxygen supplementation
timeFrame: 28-day treatment period
measure: Change from baseline in microRNA-124 levels
timeFrame: at each study visit during the 28-day treatment period
measure: Change from baseline in CRP, Troponin I & T and D-dimer
timeFrame: at each study visit during the 28-day treatment period
measure: SARS-CoV-2 viral load
timeFrame: at each study visit during the 28-day treatment period
measure: Number and rates of participants with Treatment Emergent Adverse Event
timeFrame: 28-day treatment period
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Centre hospitalier Saint Pierre
city: Brussels
country: Belgium
facility: Hôpital Erasme
city: Gent
country: Belgium
facility: UZ Gent
city: Manaus
country: Brazil
facility: Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - Instituto de Pesquisa Clínica Carlos Borborema
state: Amazonas
city: Boa Vista
country: Brazil
facility: Centro Oncológico de Roraima - CECOR - NAP
state: Roraima
city: São Paulo
country: Brazil
facility: Hospital das Clinicas da FMUSP
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Infectologia Evandro Chagas - FIOCRUZ Rio de Janeiro
city: Sao Paulo
country: Brazil
facility: Conjunto Hospitalar do Mandaqui
city: Amiens
country: France
facility: Hôpital Nord
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental de Vendée
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim Ruprecht-Karls-Universität Heid
state: Baden-Württemberg
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico - Infectious Diseases
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Paolo
state: Lombardia
city: Milano
country: Italy
facility: Ospedale Luigi Sacco, AO-PU
state: Lombardia
city: Vittorio Veneto
country: Italy
facility: Ospedale di Vittorio Veneto - Medecina generale
state: Treviso
city: Lecco
country: Italy
facility: Ospedale A. Manzonidi Lecco - ASST Lecco
city: Milano
country: Italy
facility: Ospedale Niguarda
city: Mérida
country: Mexico
facility: Consultorio médico
state: Yucatan
city: Nuevo León
country: Mexico
facility: Centro de Prevención y Rehabilitación de Enfermedades Pulmon
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Alicante
country: Spain
facility: H.G.U. Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Centre Hospitalier Universitaire de Nice
name: Eric CUA, MD
role: PRINCIPAL_INVESTIGATOR
References: