TOORAK, Australia, March 17, 2014 /PRNewswire/ -- Antisense
Therapeutics (ASX:ANP) is pleased to advise that it has commenced
dosing in its Phase I Stem Cell Mobilisation (SCM) Human Proof of
Concept trial of ATL1102, the Company's second generation antisense
drug targeting the VLA-4 receptor. The trial will assess the
safety, tolerability and effect of ATL1102 on the release of
hematopoietic stem cells (CD34+) into the blood when dosed alone
and in combination with an existing therapy (Granulocyte Colony
Stimulating Factor (G-CSF)). The randomised, open label study of
ATL1102 dosed over 5 days (given on day 1, 3 and 5) in 10 healthy
volunteers is being conducted by leading Clinical Research
Organisation, Nucleus Network at its clinical trial unit at the
Alfred Hospital, Melbourne,
Victoria. (The Study "Protocol
Synopsis" following this announcement provides further
information).
With the necessary screening, dosing and follow up of patients,
ANP anticipates that results from the trial will be reported mid
2014.
The mobilisation (release) of these stem cells from the bone
marrow into the blood is part of an important medical procedure
used to improve outcomes for patients undergoing chemotherapy to
treat certain cancers. The stem cells released into the blood are
then collected and stored before high dose chemotherapy and then
re-infused to replace those lost during chemotherapy in order to
re-establish the immune system. The basis for using ATL1102 in the
SCM indication is related to the role of VLA-4 in regulating the
release of CD34+ stem cells from the bone marrow, with another drug
that also targets VLA-4 having been shown to increase CD34+ stem
cell release in humans. In a previous study in Multiple Sclerosis
patients, ATL1102 demonstrated similar activity to that drug by
increasing CD34+ levels in the blood.
Dr Jason Lickliter, Medical
Director of Nucleus Network and Principal Investigator for the
trial said "This human Phase I trial of ATL1102 is designed to
evaluate whether ATL1102 can improve mobilization of CD34+ stem
cells when used in combination with standard mobilisation therapy
to levels that would make it clinically beneficial for use in the
collection of stem cells for transplantation. There is an
acknowledged clinical need for increasing mobilisation levels
beyond those achieved by the current therapeutic approach, and so I
am very pleased to be working with Antisense Therapeutics to assess
the merits of ATL1102 in this important clinical setting."
Antisense Therapeutics Limited CEO and Managing Director
Mark Diamond said "The stem cell
mobilisation opportunity for ATL1102 while commercially attractive
with, by our estimation, a market potential of several hundred
million dollars per annum, also presents as an excellent return on
investment proposition given costs are expected to be relatively
low for developing the drug in this indication. We believe
that positive outcomes from this trial will strongly enhance our
drug's potential for this application and naturally we relish the
opportunity to further develop a drug that can potentially provide
better outcomes for cancer patients. We look forward to
successfully conducting the study and to reporting results from
this SCM trial which are anticipated mid-year."
Protocol Synopsis
|
Title
|
A Phase I,
Randomised, Open Label Study to Assess the Safety, Tolerability,
Pharmacokinetics and Pharmacodynamics of Subcutaneous Doses of
ATL1102 Alone and in Combination with G-CSF in Healthy
Volunteers
|
|
Study
Number
|
1102SCM-CT01
|
|
Study
Design
|
Single-centre,
open-label, randomised, parallel group study
|
|
Objectives
|
- To assess the safety and tolerability
of subcutaneous doses of ATL1102 alone, and in combination with
G-CSF in healthy volunteers
- To assess the pharmacodynamics of
ATL1102 alone, and in combination with G-CSF in healthy
volunteers
- To assess the pharmacokinetics of
ATL1102 alone, and in combination with G-CSF in healthy
volunteers
|
|
Endpoints
|
- Safety and tolerability of ATL1102 in
combination with G-CSF
- Pharmacokinetic profiles of
ATL1102
- Pharmacodynamic measures including
release of CD34+ haematopoietic stem cells and progenitor
cells
|
|
Number of
patients
|
It is planned that 10
patients will be randomised to one of 3 dosing groups for the
study.
|
|
Key Patient
Criteria
|
Healthy male
volunteers between the ages of 18 and 50 years of age. BMI
between 19 and 32 kg/m2
|
|
Dosing
|
ATL1102 and G-CSF
will be delivered as subcutaneous (s.c.) injections according to
the following schedule:
- Group A (n = 3) will receive
Granulocyte-Colony Stimulating Factor (G-CSF; 10µg/kg/day) via s.c.
administration on days 1, 2, 3, 4 and 5
- Group B (n = 3) will receive ATL1102
(400 mg/day) via via s.c. administration on days 1, 3 and
5
- Group C (n = 4) will receive G-CSF
(10µg/kg/day) on days 1, 2, 3, 4 and 5 and ATL1102 (400 mg/day) on
days 1, 3 and 5.
|
|
Per Patient
Duration
|
Up to 28 days
screening, one week dosing, one week follow up
|
|
Trial
Location
|
Nucleus Network,
Melbourne, VIC.
|
|
Principal
Investigator
|
Dr Jason
Lickiter
|
|
Trial
Standard
|
GCP
|
About Stem Cell Mobilisation in Cancer treatment: stem
cell mobilization and transplantation is a medical procedure used
to improve clinical outcomes for patients undergoing chemotherapy
to treat cancer. Some chemotherapy has toxic effects on bone
marrow, so hematopoietic stem cells are collected from the blood of
the patient – or from a donor's blood – before the patient receives
chemotherapy. These collected stem cells are then stored and given
back later to replace those lost during chemotherapy (engraftment).
There are normally only a small number of stem cells in the blood,
so stem cell mobilization agents are used to increase this number
before stem cell collection from a donor or more typically from a
patient. Granulocyte colony-stimulating factor (G-CSF) is the main
agent used for hematopoietic stem cell mobilization. While G-CSF is
successful in mobilizing hematopoietic stem cells, there is often
the need for additional complimentary mobilizing therapies. The
major product used in combination with G-CSF is
Mozobil® however there is an opportunity to
improve on the level of stem cell release achieved with G-CSF alone
or in combination with Mozobil. At least 2 million CD34+
cells per kg are required for durable reconstitution of the immune
system, however greater than 5 million CD34+ cells per kg, sourced
in one or more collections, lead to improved engraftment and
patient outcomes.
ATL1102 is a second generation antisense inhibitor of
CD49d, a subunit of VLA-4 (Very Late Antigen-4). In inflammation,
white blood cells (leukocytes) move out of the bloodstream into the
inflamed tissue, for example, the Central Nervous System (CNS) in
MS, and the lung airways in asthma. The inhibition of VLA-4 may
prevent white blood cells from entering sites of inflammation,
thereby slowing progression of the disease. VLA-4 is a clinically
validated target in the treatment of MS. Antisense inhibition of
VLA-4 has demonstrated positive effects in a number of animal
models of inflammatory disease including MS with the MS animal data
having been published in a peer reviewed scientific journal.
ATL1102 was previously shown by Antisense Therapeutics to be highly
effective in reducing MS lesions in a Phase IIa clinical trial in
MS patients. The company has also lodged an International
patent application on ATL1102 based on preliminary data in mice and
humans supporting its' potential application as a stem cell
mobilization agent for use in combination with G-CSF to improve the
level of stem cell release achieved with G-CSF alone.
Antisense Therapeutics Limited (ASX: ANP) is an
Australian publicly listed biopharmaceutical drug discovery and
development company. Its mission is to create, develop and
commercialise second generation antisense pharmaceuticals for large
unmet markets. ANP has 4 products in its development pipeline that
it has in-licensed from Isis Pharmaceuticals Inc., world
leaders in antisense drug development and commercialisation -
ATL1102 (injection) which has successfully completed a Phase II
efficacy and safety trial, significantly reducing the number of
brain lesions in patients with multiple sclerosis (MS),
ATL1103 a second-generation antisense drug designed to block GHr
production and thereby lower blood IGF-I levels and is in
clinical development as a potential treatment for growth and other
GH-IGF-I disorders, ATL1102 (inhaled) which is at the
pre-clinical research stage as a potential treatment for asthma and
ATL1101 a second-generation antisense drug at the pre-clinical
stage being investigated as a potential treatment for cancer.
Contact Information:
Website: www.antisense.com.au
Managing Director: Mark Diamond +61
(3) 9827 8999
USA Investor/Media: Joshua Drumm +(1) 212 375 2664;
jdrumm@tiberend.com
Australia Investor/Media: Simon
Watkin +61 (0)413 153 272;
simon@marketconnect.com.au
SOURCE Antisense Therapeutics Limited