The fifth and final patient in the phase 1/2a clinical trial of TT-034, a ddRNAi-based therapeutic to treat hepatitis C virus infection, has been dosed, according to a news release from Benitec Biopharma Limited.
The fifth and final patient in the phase 1/2a clinical trial of TT-034, a
ddRNAi-based therapeutic to treat hepatitis C virus infection, has been
dosed, according to a news release from Benitec Biopharma Limited.
at the Duke Clinical Research Unit of Duke Clinical Research Institute
is an open-label dose escalation study that evaluates the safety and
activity of single doses of TT-034 (Benitec), a potential treatment for
HCV with a single-dose administration, in patients with chronic HCV
genotype 1 infection who have failed previous treatments, according to
the Duke Clinical Research Unit website. The trial consists of 14
patients in five sequential dose cohorts.
that was a half-log higher than patients dosed in the first cohort,
according to the release. The dose level was still below the
concentration expected to inhibit HCV viral replication, according to the release.
SOURCE Benitec Biopharma Limited
Biopharma Limited (ASX: BLT, OTC: BTEBY) is pleased to advise that the
third patient in its Phase I/IIa clinical trial of TT-034 for hepatitis C
was dosed earlier today at the Duke Clinical Research Unit (USA).
This is a significant step for this “first in man” study, and follows
review of the collective data from the first two patients by the
independent Data Safety Monitoring Board (DSMB). The DSMB determined
that the patients from the first dosing cohort were clear of any
significant treatment-related adverse events.
newly dosed patient is the first to receive the increased dose of
TT-034 (1.25 x 10^11 vg/kg, a concentration that is a half log higher
than the doses administered in the first cohort). While TT-034 is
designed as a potential “one-shot” cure for hepatitis C, the current
dose is still below that expected to inhibit viral replication and data
from the second dosing cohort are therefore expected to serve primarily
as a further safety assessment.
with previous patients, the newly dosed patient will be monitored for
six weeks and results will be reviewed by the DSMB. Should the results
indicate appropriate safety outcomes, the DSMB is expected to recommend
that the remaining two patients in the second cohort be dosed. It is
aimed to dose both at approximately the same time. The trial sites at
Duke Clinical Research Unit and University of California San Diego have identified a number of patients who have passed initial screening who can be prepared in anticipation of this outcome.
is a ddRNAi-based therapeutic, designed to treat and potentially cure
hepatitis C (HCV) with a single administration. TT-034 targets the
hepatitis C viral RNA at three separate, highly conserved sites. As such
it acts as a “triple therapy” even though it is a monotherapy, and
minimizes the ability of the virus to mutate and escape the therapy.
Once it reaches the liver cells, it enters the nucleus and produces
three separate short hairpin RNAs continuously for the lifetime of the
cell. Thus TT-034 has the potential to not only treat the existing HCV
infection, but also to guard against reinfection for months to years
without the need to re-treat. TT-034 safety and efficacy has been tested
extensively in pre-clinical in vivo studies with no adverse effects
observed at therapeutic doses.
Biopharma Limited is an ASX-listed biotechnology company (ASX: BLT;
OTC: BTEBY), which has developed a patented gene silencing technology
called DNA-directed RNA interference (ddRNAi). ddRNAi has the potential
to produce ‘single-shot’ treatments and even cures for a range of
chronic and life- threatening human conditions. Based in Sydney, Australia, with labs in Hayward CA
(USA) and collaborators and licensees around the world, the company is
developing ddRNAi-based therapeutics for diseases including hepatitis C
and B, drug resistant lung cancer and wet age-related macular
degeneration. Benitec has licensed ddRNAi to other biopharmaceutical
companies for human therapeutic applications including HIV/AIDS,
Huntington’s Disease, cancer, chronic neuropathic pain and retinitis
pigmentosa. For more information visit www.benitec.com.
SOURCE Benitec Biopharma Limited
SYDNEY, May 29, 2014 /PRNewswire/ — RNAi-based therapeutics company,
Benitec Biopharma Limited (asx:BLT) is pleased to announce that it has
dosed the first patient in its ‘first in man’, Phase I/IIa clinical
trial for TT-034, a ddRNAi-based therapeutic, designed to treat and
potentially cure hepatitis C (HCV) with a single injection.
commencement of this clinical trial of TT-034 represents a landmark in
the Company’s history. The trial is the first time Benitec’s gene
silencing technology, ddRNAi, has been used systemically in patients.
can be used safely in patients with HCV. Preclinical work in non-human
primates demonstrated very low toxicity results at therapeutically
relevant doses, and we’re hopeful that we will see the same favourable
tolerability in humans. In addition, we will be able to assess the
impact of TT-034 treatment on HCV viral load in these patients, and this
important efficacy marker constitutes one of the secondary endpoints of
study in a total of 14 patients chronically infected with HCV genotype
1. Initial patient cohorts will be treated with a sub-therapeutic dose
of TT-034 to ensure that there are no unexpected safety concerns, before
proceeding to higher, potentially therapeutic doses.
is independent of Benitec, will carefully assess the data from each
patient, in particular the safety data. The DSMB assessment will occur
after the first patient in each cohort and between cohorts, and will
determine the timing of each subsequent dosing.
The gene-silencing technology, developed by CSIRO, will be used on 14
US patients suffering from hepatitis C, in the hope it can fight off
If proved safe and effective, the treatment could allow doctors to directly place medication into a patient’s genes.
company Benitec Biopharma gained approval from the US Food and Drug
Administration for a trial of the technology, known as DNA Directed RNA
Interference. The trial will be run at Duke University and the
University of California over the next 18 months.
Researchers at Britain’s University of Westminster have developed a
means to test a cure for hepatitis C, a deadly liver disease that causes
350,000 deaths around the world each year.
Hepatitis C is caused by the hepatitis C virus HCV and, for the first
time, a drug that is believed to cure the disease is being tested on
humans. The drug, TT-034, was developed using gene therapy by an
Australian company, Benitec Biopharma.