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

Phase 2

Withdrawn

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

• Registration Number: NCT05411575
• Lead Sponsor: 4Living Biotech

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-15
• Study First Submitted QC: 2022-06-07
• Study First Posted: 2022-06-09
• Study Start: 2022-07-19
• Primary Completion: 2022-10
• Study Completion: 2022-10
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-07
• Last Update Posted: 2023-04-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	continuous intravenous infusion for 7 days of Placebo
Plerixafor	Plerixafor 20 MG/ML [Mozobil]	Plerixafor (Mozobil®) continuous intravenous infusion for 7 days

Primary Outcome Measures

Name	Time	Method
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)	Day 1- Day 28	Proportion of patients with need for invasive mechanical ventilation or death between randomization and D28

Secondary Outcome Measures

Name	Time	Method
To evaluate the efficacy of Plerixafor compared to placebo on Level of consciousness	Day 1-Day 8, Day 14, Day 28, Day 90	Level of consciousness (Alert, Voice, Pain, Unresponsive scale)
To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D28	Day 1-Day 28	Percentage of death (all-cause mortality)
To evaluate the efficacy of Plerixafor compared to placebo on Ventilator-free days between randomization and D28	Day 1-Day 28	Number of Ventilator-free days
To evaluate the efficacy of Plerixafor compared to placebo on Duration of mechanical ventilation between randomization and D90	Day 1-Day 90	Duration of invasive mechanical ventilation in survivors
To evaluate the efficacy of Plerixafor compared to placebo on Length of ICU stay between randomization and D90	Day 1-Day 90	Number of ICU stay days
To evaluate the efficacy of Plerixafor compared to placebo on SpO2 status	Day 1-Day 8, Day 14, Day 28, Day 90	Measure of SpO2 via pulse oxymetry
To evaluate the efficacy of Plerixafor compared to placebo on Safety/Lab tests	up to Day 90	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)
To evaluate the efficacy of Plerixafor compared to placebo on Respiratory/oxygenation status	Day 1-Day 8, Day 14, Day 28, Day 90	Measure of Partial pressure of oxygen (PaO2), Partial pressure of carbon dioxide (PaCO2), Bicarbonate (HCO3),
To evaluate the efficacy of Plerixafor compared to placebo on CRP, fibrinogen and D-dimers levels	Day 1, Day 3, Day 8, Day 14, Day 28	Blood CRP, fibrinogen, D-dimers levels
To evaluate the efficacy of Plerixafor compared to placebo on Safety AEs	up to Day 90	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
To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D90	Day 1-Day 90	Percentage of death (all-cause mortality)
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	Day 1-Day 90	Respiratory function at 3 months (FEV-1, FVC, PaO2, TLCO, 6-minute walk test)
To evaluate the efficacy of Plerixafor compared to placebo on Clinical improvement	Day 1, Day 8, Day 14 Day 28, Day 90	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)

Trial Locations

Locations (14)

University Hospital for Active Treatment and Emergency Medicine NI Pirogov EAD; 🇧🇬 Sofia, Bulgaria

Multiprofile Hospital for Active Treatment AD Haskovo; 🇧🇬 Haskovo, Bulgaria

Military Medical Academy Multiprofile Hospital for Active Treatment Sofia; 🇧🇬 Sofia, Bulgaria

MHAT Sveta Anna Sofia AD; 🇧🇬 Sofia, Bulgaria

Multiprofile Hospital For Active Treatment Pazardzhik AD; 🇧🇬 Pazardzhik, Bulgaria

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD; 🇧🇬 Plovdiv, Bulgaria

University First Multiprofile Hospital for Active Treatment Sofia St John the Baptist; 🇧🇬 Sofia, Bulgaria

Multiprofile Hospital for Active Treatment Dr Ivan SeliminskiSliven AD; 🇧🇬 Sliven, Bulgaria

Hôpital Haut-Lévêque; 🇫🇷 Pessac, France

University Multiprofile Hospital for Active Treatment Prof Dr Stoyan Kirkovich AD; 🇧🇬 Stara Zagora, Bulgaria

Hôpital Saint André; 🇫🇷 Bordeaux, France

Centre Hospitalier d'Argenteuil; 🇫🇷 Argenteuil, France

Centre Hospitalier Départemental de Vendée - Les Oudairies; 🇫🇷 La Roche-sur-Yon, France

Hôpital Civil de Strasbourg; 🇫🇷 Strasbourg, France