ARDS Biologics

Focused on regenerative respiratory medicine.

Title: Phase IIb/III Trial of Umbilical Cord-derived Mesenchymal Stem Cells for Patients with Acute Respiratory Distress Syndrome (“UC-MSC for ARDS”)

Mesenchymal Stem Cells (MSCs) are potent immunomodulatory cells that recognize sites of injury, limit effector T cell reactions, and positively modulate regulatory cell populations. MSCs also stimulate local tissue regeneration via paracrine effects inducing angiogenic, anti-fibrotic and remodeling responses. MSCs can be derived from a number of source tissues that include adipose tissue (AD), bone marrow (BM), placental tissue (PT), cord blood (CB) and umbilical cord (UC). The latter represent a tissue of choice for several reasons: (i) wide availability of the UC, (ii) relative ease with which UC-derived MSCs can be expanded to clinically relevant numbers, and (iii) the availability of pre-clinical and clinical data. UC-MSCs, utilized in the allogeneic setting, have demonstrated safety and efficacy in clinical trials for a number of disease conditions including autoimmune conditions and other inflammatory disorders, yielding beneficial effects in models of autoimmune Type 1 Diabetes, Systemic Lupus Erythematosus, Autoimmune Encephalomyelitis, MS, cardiac insufficiency, and organ transplantation. MSCs have been also reported to inhibit inflammation and fibrosis in the lungs (23-26) and have been recently suggested as useful to treat patients with ARDS based on their effects preventing or attenuating the immunopathogenic cytokine storm.

This is a double-blind, phase 2b/3, randomized, controlled, multi-center trial of 128 subjects with moderate to severe ARDS. Allocation to UC- MSC treatment group or control group will be based on 1:1 randomization: 64 subjects will be allocated to UC-MSC treatment group, 64 subjects to control group. Randomization will be stratified by site and by type of oxygen therapy (High Flow Oxygen/NIPPV versus mechanical ventilation). The study will test the hypothesis that UC-MSC treatment leads to an increase of the proportion of patients alive and free of respiratory failure at day 60 after randomization. The study will also estimate effects on survival, on the occurrence of Serious Adverse Events (SAEs), and on time to recovery.

 

The overall objective of this protocol is to confirm safety and determine effectiveness of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) infusions in subjects with ARDS.

The primary objective will be to assess effectiveness of UC-MSC treatment  on proportion of patients alive and free of respiratory failure at Day 60 after   randomization.

The secondary objectives will be to assess all-cause mortality at Day 60, survival at day 31, number of subjects experiencing serious adverse events (SAEs) by day 31, SAE-free survival, time to recovery (evaluated until day 60), and time to oxygen requirement equal or below 40% oxygen.

The primary endpoint will be: Proportion of patients alive and free of respiratory failure at Day 60 after randomization comparing UC-MSC therapy group versus Control group.

The secondary endpoints will be

– All-cause mortality at Day 60

– Survival at day 31,

– Number of subjects experiencing Serious Adverse Events by day 31,

– SAE-free survival

– Time to Recovery (evaluated until day 60).

– Time to oxygen requirement 40% oxygen or below

128 hospitalized subjects diagnosed with ARDS will be enrolled. Subjects of any gender, with age between 18 and 80 years, will be eligible for enrollment.