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

NCT05411575 | Withdrawn Phase 2 DMC

• 1 other identifier: 4LB-LEO-P
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 14

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.

Conditions

COVID-19 Acute Respiratory Distress Syndrome; COVID-19

Keywords

COVID-19; ARDS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D28

  Day 1-Day 28

• To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D90

  Day 1-Day 90

• To evaluate the efficacy of Plerixafor compared to placebo on Ventilator-free days between randomization and D28

  Day 1-Day 28

• To evaluate the efficacy of Plerixafor compared to placebo on Duration of mechanical ventilation between randomization and D90

  Day 1-Day 90

• To evaluate the efficacy of Plerixafor compared to placebo on Length of ICU stay between randomization and D90

  Day 1-Day 90

Study Arms (2)

Placebo

PLACEBO COMPARATOR

continuous intravenous infusion for 7 days of Placebo

Other: Placebo

Plerixafor

EXPERIMENTAL

Plerixafor (Mozobil®) continuous intravenous infusion for 7 days

Drug: Plerixafor 20 MG/ML [Mozobil]

Interventions

Plerixafor 20 MG/ML [Mozobil] DRUG

Plerixafor (Mozobil®) continuous intravenous infusion for 7 days

Plerixafor

Placebo OTHER

Placebo continuous intravenous infusion for 7 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Pregnancy or breast feeding,
• Anticipated transfer to another hospital, which is not a study site within 72 hours of randomisation,
• 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,

Sponsors & Collaborators

• 4Living Biotech: lead

Study Sites (14)

Multiprofile Hospital for Active Treatment AD Haskovo

Haskovo, 6300, Bulgaria

Location

Multiprofile Hospital For Active Treatment Pazardzhik AD

Pazardzhik, 4400, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, 4002, Bulgaria

Location

Multiprofile Hospital for Active Treatment Dr Ivan SeliminskiSliven AD

Sliven, 8800, Bulgaria

Location

University First Multiprofile Hospital for Active Treatment Sofia St John the Baptist

Sofia, 1142, Bulgaria

Location

Military Medical Academy Multiprofile Hospital for Active Treatment Sofia

Sofia, 1606, Bulgaria

Location

University Hospital for Active Treatment and Emergency Medicine NI Pirogov EAD

Sofia, 1606, Bulgaria

Location

MHAT Sveta Anna Sofia AD

Sofia, 1750, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Prof Dr Stoyan Kirkovich AD

Stara Zagora, 6000, Bulgaria

Location

Centre Hospitalier d'Argenteuil

Argenteuil, 95100, France

Location

Hôpital Saint André

Bordeaux, 33000, France

Location

Centre Hospitalier Départemental de Vendée - Les Oudairies

La Roche-sur-Yon, 85000, France

Location

Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Hôpital Civil de Strasbourg

Strasbourg, 67091, France

Location

MeSH Terms

Conditions

COVID-19

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2022
• First Posted: June 9, 2022
• Study Start: July 19, 2022
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: April 10, 2023

Record last verified: 2023-04

Locations

BU (9); FR (5)