Clinical trial NCT05411575: Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb)
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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COVID-19 Acute Respiratory Distress Syndrome
COVID-19
Keywords: COVID-19
ARDS
Lead sponsor: 4P-Pharma
Sponsor class: INDUSTRY
First posted: 2022-06-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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,

Primary outcomes:
measure: 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)
timeFrame: Day 1- Day 28
Secondary outcomes:
measure: To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D28
timeFrame: Day 1-Day 28
measure: To evaluate the efficacy of Plerixafor compared to placebo on Mortality between randomization and D90
timeFrame: Day 1-Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on Ventilator-free days between randomization and D28
timeFrame: Day 1-Day 28
measure: To evaluate the efficacy of Plerixafor compared to placebo on Duration of mechanical ventilation between randomization and D90
timeFrame: Day 1-Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on Length of ICU stay between randomization and D90
timeFrame: Day 1-Day 90
measure: 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
timeFrame: Day 1-Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on Clinical improvement
timeFrame: Day 1, Day 8, Day 14 Day 28, Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on Level of consciousness
timeFrame: Day 1-Day 8, Day 14, Day 28, Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on SpO2 status
timeFrame: Day 1-Day 8, Day 14, Day 28, Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on Respiratory/oxygenation status
timeFrame: Day 1-Day 8, Day 14, Day 28, Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on CRP, fibrinogen and D-dimers levels
timeFrame: Day 1, Day 3, Day 8, Day 14, Day 28
measure: To evaluate the efficacy of Plerixafor compared to placebo on Safety AEs
timeFrame: up to Day 90
measure: To evaluate the efficacy of Plerixafor compared to placebo on Safety/Lab tests
timeFrame: up to Day 90
Other outcomes:
Locations:
city: Haskovo
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment AD Haskovo
city: Pazardzhik
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment Pazardzhik AD
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
city: Sliven
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Dr Ivan SeliminskiSliven AD
city: Sofia
country: Bulgaria
facility: University First Multiprofile Hospital for Active Treatment Sofia St John the Baptist
city: Sofia
country: Bulgaria
facility: Military Medical Academy Multiprofile Hospital for Active Treatment Sofia
city: Sofia
country: Bulgaria
facility: University Hospital for Active Treatment and Emergency Medicine NI Pirogov EAD
city: Sofia
country: Bulgaria
facility: MHAT Sveta Anna Sofia AD
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Prof Dr Stoyan Kirkovich AD
city: Argenteuil
country: France
facility: Centre Hospitalier d'Argenteuil
city: Bordeaux
country: France
facility: Hôpital Saint André
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental de Vendée - Les Oudairies
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Strasbourg
country: France
facility: Hôpital Civil de Strasbourg
Study officials:
References: