Efficiency and Security of NIVOLUMAB Therapy in Obese Individuals With COVID-19(COrona VIrus Disease) Infection

Sponsor
Hospices Civils de Lyon
Study ID
NCT04413838
Phase
PHASE2
Status
Unknown

Conditions

  • Obesity, COVID-19 Infection

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • NIVOLUMAB — DRUG
    IV injection within 30 minutes of 24ml file (=240 mg) containing NIVOLUMAB BMS(Bristol-Myers Squibb) 10mg/ml (immune check point inhibitor targeting PD-1) on top of routine standard of care for COVID-19 infection
  • Routine standard of care — OTHER
    No intervention is planned in this arm. Patients will follow routine standard of care for the COVID-19 treatment

Study Details

Although SARS-CoV-2 (Severe Acute Respiratory Syndrome-associated coronavirus) due to COVID-19 evolves poorly towards ARDS (Acute Respiratory Distress Syndrome) and death, there is to date no validated drug available for severe forms of COVID-19. Patients with COVID-19 undergo a drastic decrease of T lymphocytes (LT) count, while the remaining ones display an "exhausted" phenotype, due to immunosuppressive pathway activation among which the Programed cell Death 1 (PD1) receptor pathways. LT exhaustion is responsible for host anergy towards viral infection and leads to increased risk of severe forms of COVID-19. Moreover, while the number of systemic LT PD1+ correlates with poor prognosis clinical stages of COVID-19 infection, healing from COVID-19 associates with LT PD1 expression normalization. Chinese epidemiologic data identified clinical risk factors of poor clinical evolution (i.e. ARDS or death), among which is found obesity, similarly to observation previously obtained during H1N1 infection (flu virus). Obese persons display meta-inflammation and immune dysfunction, a condition similar to ageing, thus termed "Inflamm-aging", thus also used during obesity. Inflamm-aging, characterized by cytotoxic LT exhaustion and reduced NK cell (Natural Killer cell) cytotoxic function secondary to PD1 pathway activation, could contribute to the poor prognosis observed during cancer and infection in obese individuals. We hypothesize that the immunocompromised profile observed during obesity contribute to their vulnerability towards COVID-19. In cancer or certain infection diseases, NIVOLUMAB, an anti-PD1 monoclonal antibody, restores exhausted LT immunity. We thus hypothesize that NIVOLUMAB-induced immunity normalization could (i) stimulate anti-viral response also during COVID-19 infection and (ii) prevent ARDS development, which has previously been associated with low LT count concomitant with increased inflammatory cytokine production. This randomized controlled therapeutic trial, using an add-on strategy to usual standard of care, aims at demonstrating the efficacy and safety of NIVOLUMAB-induced cytotoxic LT normalization, to improve clinical outcomes in hospitalized COVID-19+ adult obese individuals with low LT, since they are at risk of poor prognosis. We postulate that NIVOLUMAB will increase the number of individuals able to stop oxygen therapy at D15

Key Dates

Start date
Jun 15, 2020
Status verified
May 2020
Primary completion
Jun 15, 2021
Completion
Sep 15, 2021

Study Design

Enrollment
120 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: NIVOLUMAB on top of routine standard of care
    This correspond to COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2), hospitalized, obese (BMI≥30kg/m²), with low lymphocyte counts, without high biological probability of macrophage activation syndrome (hemoglobin \< 9.2 g/dl AND a blood platelets \< 110000/mm3 AND aspartate aminotransferase (AST) \> 30 U/l AND ferritin \> 600 mg/l) and upon oxygen (either using mask or nasal cannula) but without criteria for ICU admission benefiting from a NIVOLUMAB treatment and routine standard of care for COVID-19 infection at the time of study inclusion
  • Other: Standard of care for COVID-19 infection
    This correspond to COVID-19+ patients diagnosed upon biological testing (PCR Coronavirus SARS-CoV2), hospitalized, obese (BMI≥30kg/m²), with low lymphocyte counts, without high biological probability of macrophage activation syndrome (hemoglobin \< 9.2 g/dl AND a blood platelets \< 110000/mm3 AND AST \> 30 U/l AND ferritin \> 600 mg/l) and upon oxygen (either using mask or nasal cannula) but without criteria for ICU admission benefiting from a routine standard of care for COVID-19 infection at the time of study inclusion

Primary Outcome Measure

Patient's clinical state [ Time Frame: 15 days after randomization ]

Central Contacts