Transcript Clinical Trial Protocol: ASBI 603 A Multicenter, Randomized, DoubleBlind, Placebo-Controlled, ParallelGroup Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of SUN13837 Injection in.

Clinical Trial Protocol: ASBI 603
A Multicenter, Randomized, DoubleBlind, Placebo-Controlled, ParallelGroup Study to Evaluate the Efficacy,
Safety, and Pharmacokinetics of
SUN13837 Injection in Adult Subjects
with Acute Spinal Cord Injury
Primary Objective:
Evaluate the efficacy of SUN13837
injection versus placebo in acute
spinal cord injury (ASCI) subjects by
a comparison of the proportion of
SUN13837-treated subjects and
placebo-treated subjects who are
defined as responders.
Responder definition
A subject who has reached the
following outcome at Day 112,
either :
For cervical AIS A subjects at
baseline – an improvement of 2 or
more motor levels from baseline on
either the right or left side.
For cervical AIS B or C subjects at
baseline – a total Lower Extremity
Motor Score (LEMS) of 40 or more
points.
Study information
• Phase 2
• About 60 sites.
• Initially at an acute care hospital, and can
continue at an inpatient rehabilitation facility or
an outpatient rehabilitation therapy clinic.
• Some facilities had participated in both the
trauma and rehabilitation phases, but most, such
as Genesis, were involved in only one phase.
• Other renowned rehabilitation facilities were
Craig, Kessler, and Rusk/University of Missouri.
SUN13837
A novel small molecule under development that
exerts neuroprotective and neuroregenerative
properties similar to basic fibroblast growth
factor (bFGF) through modulation of the signal
transduction pathway of the fibroblast growth
factor receptor.
However, SUN13837 does not possess the same
proliferative effects as bFGF.
SUN13837
• A smaller, lipid soluble, molecule that makes it
more likely to cross the blood-brain barrier.
• Two phase 1 studies were conducted in the US
with the first having 48/64 subjects, and the
second having 24/32 subjects. IV infusions given
were safely tolerated. Various strength doses
were given.
• SUN13837, 2-([5-Amino-4, 6-dimethylpyrimidin2-yl] oxy)-N-(1-benzylpiperidin-4-yl)-Nmethylacetamide
Study Design
• Administration of the first dose of the study
must occur within 12 hours of injury after
informed consent obtained.
• In order to standardize dosing time, at least 5
hours but no more than 24 hours should
elapse between the first and second doses of
the study drug, including missed doses.
Study Design
• Daily dosing with the study drug was
standardized to 9 AM (1 hour) for each subject
after he/she received 1-2 doses of the study
drug initially.
• For each subject, daily IV injections were given
by a peripheral IV catheter (eventually PICC
lines were allowed).
• The study drug administration period was 2728 days with 28 total doses of the study drug
to be given IV push.
Study Design
• 22 weeks of post-dose follow-up were
planned.
• Pharmacokinetics, EKG, and motor/sensory
testing were done, along with a standard
history taking and physical examination.
• Looked at ISNCSCI levels A (C4-7) through B
and C (C3-8).
• Ages 16-80.
Study Design
• Placebo was an isotonic solution containing
sterile water for IV push injection matching in
appearance to SUN13837.
• SUN13837 treatment was 1.0 mg per kg daily
for 28 doses.
Our experience
• Worked with the University of Iowa Department
of Neurosurgery, which was the primary acute
care trauma facility and enrolled each patient. Dr.
Patrick Hitchon, MD, was the principal
investigator there.
• Patients were planned to come to GMC anywhere
from 5 to 20 days post-ASCI.
• Involved extensive interaction with the Genesis
IRB, Genesis clinical research coordinators,
pharmacists, rehabilitation nurses, rehabilitation
therapists, and physical medicine & rehabilitation
physicians.
Our experience
• Had turnover in staff that did not interfere with the
study implementation.
• Company that initially started the study of SUN13837
(Asubio) was merged to another company (DaiichiSankyo).
• Study closed with 62 subjects enrolled from five
different countries: USA, United Kingdom, Czech
Republic, France, and Spain. Canada and Norway did
not enroll any subjects.
• Genesis Medical Center was one of two community
hospitals that participated in this study.
My Thanks
• Dr. Blaine Washington, MD, who was my
associate.
• Dr. Ben Levinson, MD, who is the lead physician
investigator.
• Maite Gomez-Lopez at DP Clinical, who educated
and trained us for their study, and helped us stay
in compliance.
• Dr. Patrick Hitchon, MD, who chose Genesis
Medical Center as his inpatient rehabilitation
facility of choice to continue patients with the
study after UIHC was finished with them.
My Thanks
• Genesis IRB to allow us to participate in this study
with UIHC.
• Genesis Inpatient Rehabilitation unit and the
Genesis Day Rehabilitation clinic for their staffs
providing the time and energies, as well as their
excellent patient care.
• Genesis Clinical Research team with Desyree
Weakley, Molly Frazier, Yvonne Bonick, Sarah
Castro, and their previous colleagues for their
tireless efforts, extreme patience and
understanding, and words of encouragement.