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Heartland Unit for Neuroscience Trials
NeuroNext Network
Richard Barohn, MD- PI
Grand Rounds
University of Kansas Medical Center
2/1/2013
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NeuroNEXT Goals
 Test promising therapeutics in Phase II clinical trials
o Using biomarkers when available
o Providing results that allow for Go/No-Go decisions for Phase III trials
 Accelerate drug development through established clinical trials
infrastructure
o Responding flexibly to opportunities
o Sharing expertise between disease areas
 Decrease time/cost between trial design and trial completion
o Using a central IRB and standing master trial agreements
 Coordinate public/private sector efforts
o Testing best therapeutics, from academic or industry investigators
o Leveraging NINDS’ existing relationships with academic investigators and
patient advocacy groups
o Engaging industry participation
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NeuroNEXT: Network Designed to Efficiently
Conduct Phase II Clinical Trials
 Central IRB
o Reliance agreements between sites and CIRB
o Academic IRB (CCC at MGH) IRB of record
o One full committee protocol review
o Central adverse event management and reporting
 Standardized Master Trial Agreement
o Clinical trial costs calculated on a per-patient basis go from
CCC to sites
o Recurring issues such as publications, data, and
indemnification pre-negotiated
o Use of appropriate technology transfer agreements to
maximize industry participation and support in development
of novel therapeutics
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NeuroNEXT: Network Designed to Efficiently
Conduct Phase II Clinical Trials
 25 experienced, well-trained sites throughout the United
States
 All studies expected to use the NeuroNEXT Clinical
Study Sites
 Experienced Clinical and Data Coordinating Centers to
help investigators bring new therapies forward
 Investigators must use the Clinical and Data
Coordinating Centers for all NeuroNEXT studies
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NeuroNEXT Coordinating Centers and Clinical Sites
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Clinical Study Sites
 Albert Einstein College of Medicine
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Yeshiva
Children’s of Boston
Children's National
Columbia-Cornell
Emory
Massachusetts General Hospital
Northwestern University
Ohio State University
Oregon Health and Science
University
Swedish Health Services (Seattle)
SUNY (Buffalo, Downstate,
Upstate, and Stony Brook)
University of Alabama, Birmingham
University of California, Davis
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UCLA
University of Cincinnati
University of Colorado, Denver
University of Kansas
University of Miami
University of Pittsburgh
University of Rochester
University of Utah
University of Virginia
University of Texas, Dallas
Vanderbilt
Washington University in St. Louis
NeuroNEXT Network Infrastructure
 NIH/ NINDS
 NeuroNEXT Scientific Program Director: Elizabeth McNeil, MD,
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MSc
NeuroNEXT Administrative Program Director: Claudia Moy, PhD
Director of the Office of Clinical Research: Petra Kaufmann, MD,
MSc
Clinical Research Project Manager: Janice Cordell
Data and Safety Monitoring: A. Louise Ritz, MBA
Clinical Trials Recruitment Specialist: Jamie Roberts, MA, CCRP
Health Program Specialist: Crina Frincu, PhD
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NeuroNEXT Network Infrastructure
 Clinical Coordinating Center (CCC)
o Massachusetts General Hospital
 PI Merit Cudkowicz, MD, MSc
 Data Coordinating Center (DCC)
o University of Iowa
 PI Christopher Coffey, PhD
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Why Apply to Use NeuroNEXT
 Allows access to NeuroNEXT infrastructure
o NeuroNEXT CCC and DCC
o NeuroNEXT Central Pharmacy and Laboratory
o 25 NeuroNEXT Clinical Study Sites
 Efficient start up
o Pre-existing master trial agreements for all 25 sites
o Central IRB review administered through NeuroNEXT CCC
 Assistance with protocol and grant development
 NINDS provides infrastructure/partner provides funding
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Applying to NeuroNEXT
 Three possible mechanisms:
o Academic investigators:
 NeuroNEXT Clinical Trials (U01) (PAR-11-343).
 Upcoming Due Dates- December 3, 2012
o Industry:
 NeuroNEXT Clinical Trials (U01) (PAR-11-343); OR
 Expedited access to NeuroNEXT expertise and infrastructure
through the NeuroNEXT Infrastructure Resource Access (X01)
(PAR-11-344)
o Small businesses:
 NeuroNEXT Clinical Trials (U01) (PAR-11-343); OR
 Small Business Program: NeuroNEXT Small Business
Innovation in Clinical Trials (U44) (PAR-11-345
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Who is Eligible to Apply?
 ANYONE may apply.
 You do not have to be based at a NeuroNexT site to apply.
 If your proposal is approved for grant funding, your site becomes an
ad hoc NeuroNext site for the duration of the study/trial.
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Resources on the public website
 Clinical Study Concept Form
 Overview of solicitation/review
of proposals
 Guidelines for rigorous
study design
 Links to primary clinical sites,
CCC, DCC, and NINDS
information
 Information for academic
and industry researchers
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What To Do First…
Initial determination of project suitability for
NeuroNext will be made by NINDS.
 Let Dr. Barohn/ Pat Laubinger know about idea and strongly advise
a meeting before submitting the NeuroNext Clinical Study Concept
Synopsis Form. The form is at www.neuronext.org
 Contact Elizabeth McNeil, MD at NINDS- informal discussion of
proposal
o [email protected] or 301-496-9135
 Submit the completed NeuroNext Clinical Study Concept Synopsis
Form to Dr. McNeil at NINDS
 NINDS program staff discusses the proposed study to determine if
proposal is aligned with the overall mission and priority of NINDS.
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The Process
Proposals with good NINDS program support are referred
to the NeuroNext Executive Committee (NEC).
Permanent Members:
 CCC PI: Merit Cudkowicz, MD, MS
 DCC PI: Christopher Coffey, PhD
 NINDS Scientific Program Director: Elizabeth McNeil,MD, MS
Rotating Members:
 Clinical site PI’s: Tracey Glauser, MD; E. Clarke Haley, MD;
Karen Mardor, MD, MPH
 PIs of all approved NeuroNext studies
NeuroNext Executive Committee (NEC)
The NEC performs feasibility assessments on proposals including
 availability of a sufficient number of NeuroNEXT sites with
interest in conducting a study in specific disease population;
 availability of patient population and feasibility of conducting trial at
NeuroNEXT sites;
 assessment of regulatory requirements;
 availability of drug/placebo for the proposed trial;
 biostatistical feasibility of study/trial
Based on a majority vote of NEC members, a recommendation will be
communicated to NINDS in the form of a brief written summary.
Extramural Science Committee (ESC)
The protocol synopsis and the projected study budget is
sent to the NINDS Extramural Science Committee (ESC).
 The focus of the NINDS ESC is to review the strength of
the scientific rational and estimated budget of the
proposal.
 If approved by the ESC, then full protocol development
begins.
NeuroNext Decisions
 Protocol PI works with CCC-DCC PWG (Protocol
Working Group) to develop protocol design
 Full protocol and grant development
o Includes: assistance with biostatistics, central
pharmacy and laboratory, budget, monitoring and
other vendors as needed
 Regulatory submission at least 31 days prior to grant
submission (as needed)
 Grant submission
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Grant Applications Must Include…
 Compelling scientific evidence for evaluating the
proposed investigational agent in the disease under
study
 Proposed methodology for testing whether the
investigational agent has the expected biological effect in
study patients
 Documentation of an active IND/IDE for the
investigational agent of IND exemption, if applicable
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NeuroNEXT Concept Proposal
Preclinical
Data
Mechanism
of Action
Clinical Data
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Additional Facts…
 PI institution becomes site for their trial if not
NeuroNEXT network site
 Budget for PI and their site
 PI becomes part of NEC and Publication/Data Sharing
Committee for duration of their study
 External Statistician possible as consultant
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NeuroNEXT Applications Year 1 (10/11-12/12)
77 Proposals
submitted to
NeuroNEXT
1 Grant
FundedSMA
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42 submitted
to NEC30 approved
30 Submitted
to ESC
15 approved
9 Final grants
submitted
22 submitted for
PWGs
10 currently
active
First Grant Funded
 Principal Investigator: Steven Kolb, MD, PhD and John
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Kissel, MD, Ohio State University
Disease: Spinal Muscular Atrophy
Preliminary Aims:
SMA Biomarkers in the Immediate Postnatal Period of
Development
Approval Date: 2/29/2012
Investigators Meeting- 9/2012
As of 1/17/2013, 11 of the 15 sites has been activated
with 6 participants enrolled.
Grants Submitted
Glyburide Advantage in Malignant Edema and Stroke
(GAMES) study
 PPI: Barney Stern, MD, University of Maryland
 U01 grant submitted on April 2nd, 2012
 SEP review August 13th, 2012
 Discussing resubmission
Ibudilast (MN-166) in Subjects with Progressive MS
 PPI: Robert Fox, MD, Mellen Center for MS, Cleveland Clinic
 U01 grant submitted June 8th, 2012
 SEP review August 13th, 2012
 Received score in potentially fundable range. Will go to
February Council meeting.
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Grants Submitted
EPO Neuroprotection for Infants with Acute Brain Injury
 PPI: Shenandoah Robinson, MD, Boston Children’s Hospital
 SEP reviewed 1/7/13-pending summary statements
Ofatumumab, a Human anti-CD20 Antibody for Treatment of
Anti-MAG Neuropathy
 PPI: Norman Latov, MD, PhD, Weill Cornell Medical College
New York Presbyterian Hospital
 SEP reviewed 1/7/13-pending summary statements
Normothermia after Aneurysmal Subarachnoid Hemorrhage
 PPI: Neeraj Badjatia, MD University of Maryland
 SEP reviewed 1/7/13-pending summary statements
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Grants Submitted
An investigator-initiated clinical trial of dalfampridine in
Primary Lateral Sclerosis:
 PPI: James Wymer, MD Albany Medical College
 SEP reviewed 1/7/13-pending summary statements
Rituximab in the management of refractory autoimmune
myasthenia gravis:
 PPI: Jonathan Goldstein, MD Yale School of Medicine
 Dr. Barohn and Dr. Dimachkie are co-investigators on this
study
 U01 grant submitted on Nov 30th, 2012
 SEP reviewed 1/7/13-pending summary statements
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Grants Submitted
INT131 as an Adjunctive Therapy in Patients Currently
Treated with the ABCR Therapies (Avonex, BetaSeron,
Copaxone, Rebif) for Relapsing Remitting Multiple Scelorsis
 PPI: David Weinstein, MD, PhD, InteKrin Therapeutics, Inc
and Patricia Coyle, MD SUNY Stony Brook
 Anticipate submission of X01 and U01 grants on Dec 10th,
2012
 SEP reviewed 1/7/13-pending summary statements
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Local Site’s Role in NeuroNext
 Engage
o Clinicians
o Community
o Patients
o Advocacy groups
 Leverage CTSA resources for NINDS funding
o Dr. Barohn is Chairman of CTSA/ NeuroNext
committee
 Support new investigators
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HUNT Organization Chart
Director
Richard Barohn, MD
Associate Director
Jeffrey Burns, MD, MS
Program Manager
Pat Laubinger, MPA, BSN
Regulatory Core
Molly Gunter, MS
Director, Regulatory
Core
Project Management
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Peter Griffith, JD
Budgets/Contracts
Outreach Core
Jo Denton, MSN
Director, Outreach
Core
Asst. Coordinator
Laura Herbelin, BSc
Website and Contact Information
 National / Public Website: www.neuronext.org
 KUMC website: http://www.kumc.edu/crc/heartland-unitfor-neuroscience-trials-(hunt).html
 Local CTSA-Frontiers Website:
www.frontiersresearch.org
 Local Clinical Research Center Website:
www.kumc.edu/crc.html
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Contact Information
 Richard Barohn, MD at 913.588.6094 or
[email protected]
 Jeffrey Burns, MD, MS at 913.588.0682 or
[email protected]
 Pat Laubinger, MPA, BSN at 913.588.0685 or
[email protected]
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HUNT - University of Kansas Medical Center