HUNTHeartland 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 availableo Providing results that allow for Go/No-Go decisions for Phase III trials

Accelerate drug development through established clinical trials infrastructureo Responding flexibly to opportunitieso Sharing expertise between disease areas

Decrease time/cost between trial design and trial completiono Using a central IRB and standing master trial agreements

Coordinate public/private sector effortso Testing best therapeutics, from academic or industry investigatorso 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 CIRBo Academic IRB (CCC at MGH) IRB of recordo One full committee protocol reviewo Central adverse event management and reporting

Standardized Master Trial Agreemento Clinical trial costs calculated on a per-patient basis go from

CCC to siteso Recurring issues such as publications, data, and

indemnification pre-negotiatedo 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-

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

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,

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 infrastructureo NeuroNEXT CCC and DCCo NeuroNEXT Central Pharmacy and Laboratoryo 25 NeuroNEXT Clinical Study Sites

Efficient start upo Pre-existing master trial agreements for all 25 siteso 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.orgContact Elizabeth McNeil, MD at NINDS- informal discussion of proposal

o mcneilde@ninds.nih.gov or 301-496-9135 Submit the completed NeuroNext Clinical Study Concept Synopsis Form to Dr. McNeil at NINDSNINDS 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, MSDCC PI: Christopher Coffey, PhDNINDS 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 developmento 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

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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)

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First Grant Funded

Principal Investigator: Steven Kolb, MD, PhD and John 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 MSPPI: 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.HUNT

Grants SubmittedEPO 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 statementsRituximab in the management of refractory autoimmune myasthenia gravis: PPI: Jonathan Goldstein, MD Yale School of MedicineDr. 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 ScelorsisPPI: 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

EngageoCliniciansoCommunityoPatientsoAdvocacy groups

Leverage CTSA resources for NINDS fundingoDr. Barohn is Chairman of CTSA/ NeuroNext

committee

Support new investigators

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DirectorRichard Barohn, MD

Associate Director Jeffrey Burns, MD, MS

Program ManagerPat Laubinger, MPA, BSN

Regulatory Core

Molly Gunter, MSDirector, Regulatory

CoreProject Management

Peter Griffith, JDBudgets/Contracts

Outreach Core

Jo Denton, MSNDirector, Outreach

Core

Asst. CoordinatorLaura Herbelin, BSc

HUNT Organization Chart

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Website and Contact Information

National / Public Website: www.neuronext.org

KUMC website: http://www.kumc.edu/crc/heartland-unit-for-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 rbarohn@kumc.edu

Jeffrey Burns, MD, MS at 913.588.0682 or jburns2@kumc.edu

Pat Laubinger, MPA, BSN at 913.588.0685 or plaubinger@kumc.edu

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