Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb) (LEONARDO)

A Randomized, Double-blind, Placebo-controlled, Two Parallel Groups, International Multicenter Trial to Evaluate the Effect of Plerixafor in Acute Respiratory Failure Related to COVID-19.

This phase IIb study, LEONARDO is a multicenter, randomized, double-blind, placebo- controlled, parallel group study, to assess the therapeutic efficacy and safety of Plerixafor in patients over 18 years of age,

• with acute respiratory failure related to COVID-19 and
• Recently admitted in ICU or equivalent structure (within 48 hours) for COVID-19 related respiratory failure
• without invasive mechanical ventilation and
• requiring oxygen support ≥ 5L/min to obtain a transcutaneous O2 saturation > 94% A total of 150 participants, will be randomized in a 2:1 ratio to receive either Plerixafor (n=100) or placebo (n=50) as a continuous IV infusion for 7 days (from D1 to D8) in addition to standard of care (e.g. glucocorticoids...).

Safety data will be reviewed by an independent Data and Safety Monitoring Board (DSMB) during the study.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19; COVID-19 Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Placebo; Drug: Plerixafor 20 MG/ML [Mozobil]

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Haskovo, Bulgaria, 6300
    • Multiprofile Hospital for Active Treatment AD Haskovo
  • Pazardzhik, Bulgaria, 4400
    • Multiprofile Hospital For Active Treatment Pazardzhik AD
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
  • Sliven, Bulgaria, 8800
    • Multiprofile Hospital for Active Treatment Dr Ivan SeliminskiSliven AD
  • Sofia, Bulgaria, 1142
    • University First Multiprofile Hospital for Active Treatment Sofia St John the Baptist
  • Sofia, Bulgaria, 1606
    • Military Medical Academy Multiprofile Hospital for Active Treatment Sofia
  • Sofia, Bulgaria, 1606
    • University Hospital for Active Treatment and Emergency Medicine NI Pirogov EAD
  • Sofia, Bulgaria, 1750
    • MHAT Sveta Anna Sofia AD
  • Stara Zagora, Bulgaria, 6000
    • University Multiprofile Hospital for Active Treatment Prof Dr Stoyan Kirkovich AD
• France
  • Argenteuil, France, 95100
    • Centre Hospitalier D'Argenteuil
  • Bordeaux, France, 33000
    • Hopital Saint André
  • La Roche-sur-Yon, France, 85000
    • Centre Hospitalier Départemental de Vendée - Les Oudairies
  • Pessac, France, 33604
    • Hôpital Haut-Lévêque
  • Strasbourg, France, 67091
    • Hôpital Civil de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥ 18 years of age,
• Using contraceptive consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Willing and able to provide written informed consent (or provided by legally acceptable representative if he/she is present and if in line with local regulations),
• Admitted in ICU within 48 hours before randomization for COVID-19 related respiratory failure. (ICU or equivalent medical structure according to country specificities e.g., Acute Respiratory Care Unit, High Dependency Care Unit if they can provide: continuous IV infusion,continuous ECG, respiratory rate, percutaneous oxygen saturation screen monitoring, high flow nasal oxygen)
• Not requiring immediate (within 24-36 hours) invasive mechanical ventilation according to investigator's judgment,
• Confirmed pneumoniae due to SARS-CoV-2, Laboratory-confirmed SARS-CoV-2 infection as determined by RT-PCR (in nasopharynx or throat samples) or other commercial or public health assay in any specimen, performed within 2 weeks prior to randomization,
• Acute respiratory failure requiring oxygen support (≥ 5L/min) to achieve a transcutaneous oxygen saturation > 94%,
• Estimated glomerular filtration rate (eGFR) > 50 mL/min/1.73m2 by the CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration) equation.

Exclusion Criteria:

• Pregnancy or breast feeding,
• Anticipated transfer to another hospital, which is not a study site within 72 hours of randomisation,
• Need for Invasive mechanical ventilation at time of inclusion,
• Evidence of uncontrolled bacterial pneumopathy or active infection other than SARS-Cov-2 (laboratory confirmation),
• Primitive pulmonary arterial hypertension,

• Cardio-vascular co-morbidity:

  • History of vascular ischemic events (myocardial infarction or stroke) or congestive heart failure or peripheral arterial disease,
  • History or current significant cardiac rhythm disorders (e.g., ventricular tachycardia),
  • Known medical history of proven symptomatic postural hypotension,
• Known cancer (solid or blood) in the last 5 previous years or previous haematological disorders (malignancies and other chronic conditions) or having received bone marrow transplant,

• Inadequate haematological function defined by:

  • Neutrophil count < 1.0 x 109/L,
  • Haemoglobin < 9.0 g/dL (90 g/L),
  • Platelets < 100 x 109/L,
• Kaliemia < 3.5 mmol/L and/or total Calcemia < 2.2 mmol/L,
• Inadequate hepatic function defined by Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) > 3 x upper limit of normal (ULN) and/or Total bilirubin > 2 x ULN,
• Patients with known allergy to Plerixafor or its excipients.
• Previous (within 4 weeks) or current participation in another clinical study other than an observational study.
• Patients with auto immune disease treated or not,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; continuous intravenous infusion for 7 days of Placebo	Other: Placebo; Placebo continuous intravenous infusion for 7 days
Experimental: Plerixafor; Plerixafor (Mozobil®) continuous intravenous infusion for 7 days	Drug: Plerixafor 20 MG/ML [Mozobil]; Plerixafor (Mozobil®) continuous intravenous infusion for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To demonstrate that Plerixafor is able to reduce the need for invasive mechanical ventilation or death in severe COVID-19 patients admitted in Intensive Care Unit (ICU)	Proportion of patients with need for invasive mechanical ventilation or death between randomization and D28	Day 1- Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D28	Percentage of death (all-cause mortality)	Day 1-Day 28
To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D90	Percentage of death (all-cause mortality)	Day 1-Day 90
To evaluate the efficacy of Plerixafor compared to placebo on Ventilator-free days between randomization and D28	Number of Ventilator-free days	Day 1-Day 28
To evaluate the efficacy of Plerixafor compared to placebo on Duration of mechanical ventilation between randomization and D90	Duration of invasive mechanical ventilation in survivors	Day 1-Day 90
To evaluate the efficacy of Plerixafor compared to placebo on Length of ICU stay between randomization and D90	Number of ICU stay days	Day 1-Day 90
To evaluate the efficacy of Plerixafor compared to placebo on Respiratory function including FEV1, FVC, PaO2 and Transfer Lung Capacity for carbon monoxide (TLCO), 6-minute walk test	Respiratory function at 3 months (FEV-1, FVC, PaO2, TLCO, 6-minute walk test)	Day 1-Day 90
To evaluate the efficacy of Plerixafor compared to placebo on Clinical improvement	Ordinal Scale for Clinical Improvement (Clinical improvement: 7-point ordinal scale of the WHO Master Protocol (WHO, 2020). 1: not hospitalized up to 7:death)	Day 1, Day 8, Day 14 Day 28, Day 90
To evaluate the efficacy of Plerixafor compared to placebo on Level of consciousness	Level of consciousness (Alert, Voice, Pain, Unresponsive scale)	Day 1-Day 8, Day 14, Day 28, Day 90
To evaluate the efficacy of Plerixafor compared to placebo on SpO2 status	Measure of SpO2 via pulse oxymetry	Day 1-Day 8, Day 14, Day 28, Day 90
To evaluate the efficacy of Plerixafor compared to placebo on Respiratory/oxygenation status	Measure of Partial pressure of oxygen (PaO2), Partial pressure of carbon dioxide (PaCO2), Bicarbonate (HCO3),	Day 1-Day 8, Day 14, Day 28, Day 90
To evaluate the efficacy of Plerixafor compared to placebo on CRP, fibrinogen and D-dimers levels	Blood CRP, fibrinogen, D-dimers levels	Day 1, Day 3, Day 8, Day 14, Day 28
To evaluate the efficacy of Plerixafor compared to placebo on Safety AEs	Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs), incidence of treatment on discontinuation and withdrawals due to TEAEs	up to Day 90
To evaluate the efficacy of Plerixafor compared to placebo on Safety/Lab tests	Quantification of White Blood Cells count and differential, Red Blood Cells count, hemoglobin level, Mean Corpuscular Volume, Reticulocyte and Platelet counts . Blood Chemistry (Creatinine, AST, ALT, total bilirubin, Potassium, total Calcium)	up to Day 90

Collaborators and Investigators

• Sponsor: 4Living Biotech

Study record dates

Study Major Dates

• Study Start (Anticipated): July 19, 2022
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: May 15, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; ARDS
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: 4LB-LEO-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No