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Heartland Unit for Neuroscience Trials

NeuroNext Network HUNT 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

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Central IRB

o o o o Reliance agreements between sites and CIRB Academic IRB (CCC at MGH) IRB of record One full committee protocol review 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 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

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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 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

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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 42 submitted to NEC 30 approved 30 Submitted to ESC 15 approved 1 Grant Funded SMA

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9 Final grants submitted 22 submitted for PWGs 10 currently active

First Grant Funded

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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

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(GAMES) study

  PPI: Barney Stern, MD, University of Maryland U01 grant submitted on April 2 nd , 2012 SEP review August 13 th , 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 8 th , 2012 SEP review August 13 th , 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 30 th , 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 10 th , 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 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

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-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 [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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