Phase I, randomized, parallel group, placebo control, unicentric, interventional study to assess the effect of expanded human allogeneic adipose-derived mesenchymal adult stem cells on the human response to lipopolysaccharide in human volunteers

Preclinical studies have indicated that mesenchymal stem cells can exert
beneficial tissue-protective anti-inflammatory effects in inflammation. In the
current study we seek to obtain proof-of-principle for the anti-inflammatory
efficacy of mesenchymal stem cells in humans by using a well-established model
of human inflammation. In this model, endotoxin (lipopolysaccharide, LPS) is
administered intravenously, which produces a transient inflammatory response
that can be measured by sensitive laboratory techniques. By infusing part of
the study population with mesenchymal stem cells we intend to determine whether
this intervention indeed can inhibit inflammatory responses in humans.

To investigate the effect of expanded adipose-derived allogeneic adult stem
cells (eASCs) on the inflammatory response to intravenous LPS in humans.

Phase I, randomized, parallel group, placebo control, unicentric,
interventional study. Thirty two healthy male volunteers aged between 18-35
years will be randomized into the eASCs or placebo group at a 3:1 ratio. The
treatment administration will be infused intravenously to the following groups
after randomization:
• First arm: 250,000 cells/kg
• Second arm: 1 million cells/kg
• Third arm: 4 million cells/kg
• Fourth arm: placebo
An hour after the end of the eASCs administration, all subjects will be given
an intravenous dose of LPS (2 ng/kg). Subjects will be allowed to leave in the
evening once deemed clinically stable by the investigator.

Suspension of expanded adipose-derived allogeneic adult stem cells (eASCs) at a
single dose of 250,000 cells/kg, 1 million cells/kg or 4 million cells/kg by
intravenous infusion after suspension in Ringer's lactate solution (8 per
group; 8 subjects will receive Ringer*s lactate solution only).
Endotoxin (LPS): a single intravenous injection (2 ng/kg) in all 32 subjects.

The burden of this study includes a screening visit, one day hospital
admittance and a follow up visit. Infusion of eASCs has been well tolerated in
the Phase Ib/IIa carried out by the sponsor in another indication. LPS
administration will induce complaints consisting mainly of myalgia, headache,
fever and nausea that diminish within 6 hours. Considering the extensive
experience with this model, risks are minimal. Subjects will receive two
peripheral intravenous catheters for fluid and eASCs or placebo infusion and
for blood draws respectively (risk of pain and local hematoma). Future patients
with sepsis may benefit from the outcome of this study, as its ultimate aim is
to develop new therapeutic strategies to restore the deregulated immune
response.