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

Primary Purpose

COVID-19 Acute Respiratory Distress Syndrome, COVID-19

Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Plerixafor 20 MG/ML [Mozobil]
Placebo
Sponsored by
4Living Biotech
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 Acute Respiratory Distress Syndrome focused on measuring COVID-19, ARDS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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,

Sites / Locations

  • Multiprofile Hospital for Active Treatment AD Haskovo
  • Multiprofile Hospital For Active Treatment Pazardzhik AD
  • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
  • Multiprofile Hospital for Active Treatment Dr Ivan SeliminskiSliven AD
  • University First Multiprofile Hospital for Active Treatment Sofia St John the Baptist
  • Military Medical Academy Multiprofile Hospital for Active Treatment Sofia
  • University Hospital for Active Treatment and Emergency Medicine NI Pirogov EAD
  • MHAT Sveta Anna Sofia AD
  • University Multiprofile Hospital for Active Treatment Prof Dr Stoyan Kirkovich AD
  • Centre Hospitalier d'Argenteuil
  • Hôpital Saint André
  • Centre Hospitalier Départemental de Vendée - Les Oudairies
  • Hôpital Haut-Lévêque
  • Hôpital Civil de Strasbourg

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Plerixafor

Arm Description

continuous intravenous infusion for 7 days of Placebo

Plerixafor (Mozobil®) continuous intravenous infusion for 7 days

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D28
Percentage of death (all-cause mortality)
To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D90
Percentage of death (all-cause mortality)
To evaluate the efficacy of Plerixafor compared to placebo on Ventilator-free days between randomization and D28
Number of Ventilator-free days
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
To evaluate the efficacy of Plerixafor compared to placebo on Length of ICU stay between randomization and D90
Number of ICU stay days
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)
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)
To evaluate the efficacy of Plerixafor compared to placebo on Level of consciousness
Level of consciousness (Alert, Voice, Pain, Unresponsive scale)
To evaluate the efficacy of Plerixafor compared to placebo on SpO2 status
Measure of SpO2 via pulse oxymetry
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),
To evaluate the efficacy of Plerixafor compared to placebo on CRP, fibrinogen and D-dimers levels
Blood CRP, fibrinogen, D-dimers levels
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
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)

Full Information

First Posted
May 15, 2022
Last Updated
April 7, 2023
Sponsor
4Living Biotech
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1. Study Identification

Unique Protocol Identification Number
NCT05411575
Brief Title
Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb)
Acronym
LEONARDO
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Withdrawn
Why Stopped
No participants Enrolled
Study Start Date
July 19, 2022 (Anticipated)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
October 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
4Living Biotech

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Acute Respiratory Distress Syndrome, COVID-19
Keywords
COVID-19, ARDS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
continuous intravenous infusion for 7 days of Placebo
Arm Title
Plerixafor
Arm Type
Experimental
Arm Description
Plerixafor (Mozobil®) continuous intravenous infusion for 7 days
Intervention Type
Drug
Intervention Name(s)
Plerixafor 20 MG/ML [Mozobil]
Intervention Description
Plerixafor (Mozobil®) continuous intravenous infusion for 7 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo continuous intravenous infusion for 7 days
Primary Outcome Measure Information:
Title
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)
Description
Proportion of patients with need for invasive mechanical ventilation or death between randomization and D28
Time Frame
Day 1- Day 28
Secondary Outcome Measure Information:
Title
To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D28
Description
Percentage of death (all-cause mortality)
Time Frame
Day 1-Day 28
Title
To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D90
Description
Percentage of death (all-cause mortality)
Time Frame
Day 1-Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on Ventilator-free days between randomization and D28
Description
Number of Ventilator-free days
Time Frame
Day 1-Day 28
Title
To evaluate the efficacy of Plerixafor compared to placebo on Duration of mechanical ventilation between randomization and D90
Description
Duration of invasive mechanical ventilation in survivors
Time Frame
Day 1-Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on Length of ICU stay between randomization and D90
Description
Number of ICU stay days
Time Frame
Day 1-Day 90
Title
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
Description
Respiratory function at 3 months (FEV-1, FVC, PaO2, TLCO, 6-minute walk test)
Time Frame
Day 1-Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on Clinical improvement
Description
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)
Time Frame
Day 1, Day 8, Day 14 Day 28, Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on Level of consciousness
Description
Level of consciousness (Alert, Voice, Pain, Unresponsive scale)
Time Frame
Day 1-Day 8, Day 14, Day 28, Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on SpO2 status
Description
Measure of SpO2 via pulse oxymetry
Time Frame
Day 1-Day 8, Day 14, Day 28, Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on Respiratory/oxygenation status
Description
Measure of Partial pressure of oxygen (PaO2), Partial pressure of carbon dioxide (PaCO2), Bicarbonate (HCO3),
Time Frame
Day 1-Day 8, Day 14, Day 28, Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on CRP, fibrinogen and D-dimers levels
Description
Blood CRP, fibrinogen, D-dimers levels
Time Frame
Day 1, Day 3, Day 8, Day 14, Day 28
Title
To evaluate the efficacy of Plerixafor compared to placebo on Safety AEs
Description
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
Time Frame
up to Day 90
Title
To evaluate the efficacy of Plerixafor compared to placebo on Safety/Lab tests
Description
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)
Time Frame
up to Day 90

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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,
Facility Information:
Facility Name
Multiprofile Hospital for Active Treatment AD Haskovo
City
Haskovo
ZIP/Postal Code
6300
Country
Bulgaria
Facility Name
Multiprofile Hospital For Active Treatment Pazardzhik AD
City
Pazardzhik
ZIP/Postal Code
4400
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment Dr Ivan SeliminskiSliven AD
City
Sliven
ZIP/Postal Code
8800
Country
Bulgaria
Facility Name
University First Multiprofile Hospital for Active Treatment Sofia St John the Baptist
City
Sofia
ZIP/Postal Code
1142
Country
Bulgaria
Facility Name
Military Medical Academy Multiprofile Hospital for Active Treatment Sofia
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
University Hospital for Active Treatment and Emergency Medicine NI Pirogov EAD
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
MHAT Sveta Anna Sofia AD
City
Sofia
ZIP/Postal Code
1750
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment Prof Dr Stoyan Kirkovich AD
City
Stara Zagora
ZIP/Postal Code
6000
Country
Bulgaria
Facility Name
Centre Hospitalier d'Argenteuil
City
Argenteuil
ZIP/Postal Code
95100
Country
France
Facility Name
Hôpital Saint André
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
Centre Hospitalier Départemental de Vendée - Les Oudairies
City
La Roche-sur-Yon
ZIP/Postal Code
85000
Country
France
Facility Name
Hôpital Haut-Lévêque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Hôpital Civil de Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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