“We are very pleased in achieving this major
milestone of filing our IND for a Phase 3
confirmatory study to evaluate Bucillamine in
the treatment of patients with mild-moderate
COVID-19, which was based on the recommendation
from the U.S. FDA from our pre-IND meeting
earlier this year,” said Michael Frank, Revive’s
Chief Executive Officer. “We are preparing
plans for initiating the Phase 3 study upon the
IND becoming active by the U.S. FDA and we look
forward to advancing Bucillamine as a potential
new treatment option for patients with a
confirmed diagnosis of COVID-19 globally.”
Phase 3
Confirmatory Clinical Study Design
The Phase 3 confirmatory clinical study titled,
“A Multi-Center, Randomized, Double-Blind,
Placebo-Controlled Study of Bucillamine in
Patients with Mild-Moderate COVID-19”, will
enroll up to 800 patients that will be
randomized 1:1:1 to receive Bucillamine 100 mg
three times a day (“TID”), Bucillamine 200 mg
TID or placebo TID for up to 14 days. The
primary objective is to compare frequency of
hospitalization and mortality in patients with
mild-moderate COVID-19 receiving Bucillamine
therapy with those receiving placebo. The
primary endpoint is the proportion of patients
with the following outcomes attributed to
COVID-19 from time of the first dose through Day
28 following randomization: death, alive and
hospitalized, and alive and not hospitalized.
Efficacy will be assessed by comparison of
clinical outcome (death and hospitalization),
disease severity using the eight-category
National Institute of Allergy and Infectious
Diseases (“NIAID”) COVID ordinal scale,
supplemental oxygen use, and progression of
COVID‑19 between patients receiving
standard-of-care plus Bucillamine (high dose
and/or low dose) and patients receiving
standard-of-care plus placebo. Safety will
be assessed by incidence and severity of adverse
events and treatment-emergent adverse events
(including serious adverse events and adverse
events of special interest), laboratory values
(hematology and serum chemistry), vital signs
(heart rate, respiratory rate, and temperature),
and peripheral oxygen saturation.
An interim analysis will be performed by an
Independent Data and Safety Monitoring Board
(“DSMB”) after 210 patients have been treated
and followed up for a total of 28 days after
randomization. The better performing
Bucillamine dose at the interim analysis will be
selected and patients will then be randomized
2:1 to the selected Bucillamine dose or placebo.
Additional interim analyses will be performed
after 300, 400, 500, 600, and 700 patients have
reached this same post-treatment timepoint.
The independent DSMB will actively monitor
interim data for the ongoing safety of patients
and will recommend continuation, stopping or
changes to the conduct of the study based on the
interim analysis reports.
Scientific
Rationale of Bucillamine for COVID-19
Preclinical and clinical studies have
demonstrated that reactive oxygen species
contribute to pulmonary inflammation, cytokine
dysregulation, and acute lung injury.1 N-acetyl-cysteine
(NAC) has been shown to significantly attenuate
clinical symptoms in respiratory viral
infections in animals and humans, primarily via
donation of thiols to increase antioxidant
activity of cellular glutathione2,3,4,5.
Bucillamine
(N-(mercapto-2-methylpropionyl)-l-cysteine) has
a well-known safety profile and is prescribed in
the treatment of rheumatoid arthritis in Japan
and South Korea for over 30 years. Bucillamine,
a cysteine derivative with two thiol groups, has
been shown to be 16 times more potent as a thiol
donor in vivo than NAC 6.
Bucillamine is non-toxic with high cellular
permeability. The basis of the clinical study
will analyze if Bucillamine has the potential,
via increasing glutathione activity and other
anti-inflammatory activity, to lessen the
destructive consequences of SARS-CoV2 infection
in the lungs and attenuate the clinical course
of COVID-19.
The Company is not making any express or implied
claims that its product has the ability to
eliminate or cure COVID-19 (SARS-2 Coronavirus)
at this time.
About Revive Therapeutics Ltd.
Revive is a life sciences company focused on the
research and development of therapeutics for
infectious diseases and rare disorders, and it
is prioritizing drug development efforts to take
advantage of several regulatory incentives
awarded by the FDA such as Orphan Drug, Fast
Track, Breakthrough Therapy and Rare Pediatric
Disease designations. Currently, the Company is
exploring the use of Bucillamine for the
potential treatment of infectious diseases, with
an initial focus on severe influenza and
COVID-19. With its recent acquisition of
Psilocin Pharma Corp., Revive is advancing the
development of Psilocybin-based therapeutics in
various diseases and disorders. Revive’s
cannabinoid pharmaceutical portfolio focuses on
rare inflammatory diseases and the company was
granted FDA orphan drug status designation for
the use of Cannabidiol (CBD) to treat autoimmune
hepatitis (liver disease) and to treat ischemia
and reperfusion injury from organ
transplantation. For more information, visit www.ReviveThera.com.
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