Multicentric, Randomized Study to Assess Safety and Efficacy of Centhaquine in Patients With ARDS

This is a multicentric, randomized, double-blind, placebo-controlled phase-II clinical study to assess the safety and efficacy of centhaquine as an adjuvant to the standard of care in patients with moderate to severe ARDS. Approximately 10 study centers in the United States will participate in the study. For an individual patient, the duration of the study will be 60 days, including 3 study visits: visit 1/Day 1 (screening/randomization/baseline/treatment visit), visit 2/Day 28, and visit 3/End of Study (Day 60). At visit 1, approximately 80 eligible patients will be randomized 1:1 into 2 treatment groups of 40 each after meeting the eligibility criteria. A total of 40 patients will be enrolled in the centhaquine group (Group 1) and a total of 40 patients in the control group (Group 2):

• Group 1 (Active Group): Centhaquine (Dose: 0.01 mg/kg) + Standard of care
• Group 2 (Control group): Equal volume of Normal Saline + Standard of care In both treatment groups, patients will be provided with the standard of care. Centhaquine or Equal volume of Normal Saline will be administered intravenously after randomization to patients meeting the eligibility criteria. In the centhaquine group, centhaquine (0.01 mg/kg) dose will be administered as an intravenous (IV) infusion over 1 hour in 100 mL of normal saline. An additional dose of centhaquine will be administered on Day 2 if oxygenation and/or vasopressor support is required, but not before 24 hours of the previous dose (maximum 2 doses at an interval of 24 hours can be administered). In the control group, equal volume of normal saline will be administered as an intravenous (IV) infusion over 1 hour post-randomization. Conditions of administration will remain the same as for the centhaquine group. All subjects will be closely monitored during and after infusion. Vital signs will be monitored every 10 minutes during infusion. In the event of worsening hemodynamics or respiratory status, the infusion will be discontinued. Each subject will be monitored closely and followed up throughout his/her hospitalization. Moreover, he/she will be assessed for safety and efficacy parameters over 60 days from randomization.

Inclusion criteria

A subject will be eligible for inclusion in the study if he/she fulfills the following criteria:

• Adult male or female aged 18 years or older
• Hospitalized in the ICU diagnosed with moderate to severe ARDS having a PaO2/FiO2 ratio of < 200 mmHg or the SPO2/FiO2 ratio of ≤ 235( if SPO2 ≤ 97 %) with PEEP ≥ 5 cm H20 include the patient receiving invasive /non-invasive ventilation (NIV/CPAP).
• The first dose of the study drug should be administered within 48 hours of confirming moderate to severe ARDS.
• Requires vasopressor support
• Written informed consent

Exclusion criteria

A subject will not be eligible for inclusion in this study if he/she meets any of the following exclusion criteria:

• Receiving or expected to receive extracorporeal membrane oxygenation or high-frequency oscillatory ventilation
• Confirmed pregnancy
• Breast feeding
• Participating in another interventional study
• Requires or having the renal replacement therapy
• Hepatic failure (Child-Pugh scores B and C)