Reducing The Impact Of Chronic Kidney Disease (CKD): Opportunities For Randomized Clinical Trials

AGENDA

DAY 1: Tuesday, July 19, 2011

7:00 – 8:00 a.m.	Registration

8:00 – 8:15 a.m.	Opening Remarks and Objectives Dr. Robert Star and Dr. Michael Flessner

8:15 – 9:45 a.m.	State-of-the-Art Lectures Moderator: Dr. Glenn Chertow Lessons from CRIC and CKid: Defining Risk Factors Relevant to CKD Trials Dr. Harold Feldman and Dr. Susan Furth Lessons from CKD Trials (TREAT, AASK, RENALL) Dr. Robert Toto Why Good Trials Go Bad Dr. Tom Greene

9:45 – 10:00 a.m.	BREAK

10:00 – 12:30 p.m.	Challenges in Clinical Trial Design (I) – Planning Studies for CKD Moderator: Dr. Laura Dember Selection of Study Populations: Prevention or Interventions to Slow Progression? Dr. Julie Lewis Renal Outcomes for Phase III Trials Dr. Lawrence Appel Biomarkers for CKD Progression or Risk of Progression Dr. Patrick Murray Effect Size and Sample Size Calculations Dr. Glenn Chertow Adaptive Designs to Increase Efficiency for Phase II/III Trials Dr. Michael Rosenblum SPRINT: High Risk CKD Subgroup Within a Larger Clinical Trial Dr. Alfred Cheung and Dr. David Reboussin

12:30 – 1:15 p.m.	Lunch (Pre-Purchased Box Lunches in Breakout Rooms)

1:15 – 3:40 p.m.	Therapies in Phase II/Pilot Studies Moderator: Dr. Flessner Allopurinol Dr. Allesandro Doria Antioxidants Dr. Jonathan Himmelfarb Bicarbonate Dr. Michal Melamed Mineralocorticoid Receptor Blockers Dr. Robert Toto Non-Pharmacologic Therapies: Glucose Control, Weight Loss, and Sodium Restriction Dr. William Mitch Pentoxifylline Dr. Robert Perkins Pirfenidone Dr. Kumar Sharma Vitamin D/Phosphate Binding/Dietary Intervention Dr. Geoff Block

3:45 – 5:15 p.m.	Breakout Sessions Purpose: To discuss the critical design elements that are required to bring a medication or maneuver to a Phase III trial. Topics for Individual Breakout Sessions: Group 1 Trial in Children: Agent To Prevent Progression Moderators: Dr. Susan Furth, Dr. Russell Chesney, Dr. James Chan, Dr. Frederick Kaskel, Dr. Lynne Yao, and Dr. David Reboussin Group 2 Trial in Adults with Bicarbonate Moderators: Dr. Michal Melamed, Dr. Donald Wesson, and Dr. Tom Greene Group 3 Trial in Adults with Pentoxifylline Moderators: Dr. Robert Perkins and Dr. Linda Fried, NIH Biostatistician Group 4 Trial in Adults with Mineralocorticoid Receptor Blocker Moderators: Dr. Robert Toto, Dr. Tom Hostetter, and Dr. Michael Rosenblum Group 5 Trial in Adults with Phosphate Control/Vitamin D: Moderators: Dr. Myles Wolf, Dr. Rajnish Mehrota, Dr. Ravi Thadani, and Dr. Glenn Chertow, NIH Biostatistician Each Group Will Consider the Following Issues: Define Trial Question: Preliminary Data? Renal Endpoints for Phase III CKD Trial Proteinuria as an endpoint? Are there other surrogate endpoints? Creatinine (or cystatin C)-based endpoints: Doubling? Slope? Are CKD staging tools feasible endpoints? What are the obstacles that have prevented the design and execution of outcome studies for renal-specific endpoints? Non-Renal Endpoints for Phase III CKD Trials Non-renal endpoints (CVD, mortality, hospitalization) Which should be used in either Phase II or Phase III studies? Should these be primary or secondary endpoints in Phase III studies? Patient Selection and Recruitment Inclusion/exclusion criteria (Early disease vs. late disease) Impact of patient selection on design of study Should a trial be restricted to proteinuric disease or have a stratum with a target proportion with proteinuria? If yes, how would proteinuria be defined? Is the recruitment strategy feasible? Biomarkers for risk stratification Incorporation of Protocolized Adjunctive Care (Will this agent be added to ACEI or ARB or be substituted for the current standard of care?) Adverse Events/Pilot and Feasibility Issues: Dose Selection Sample Size and Power

5:15 – 6:00 p.m.	Preliminary Reports From the Breakout Sessions and General Discussion

6:00 p.m.	Adjournment

DAY 2: Wednesday, July 20, 2011

7:00 – 8:00 a.m.	Registration

8:00 – 9:00 a.m.	Government-Academic-Industry Partnerships Moderator: Dr. Michael Flessner Regulatory Issues: FDA Viewpoint Dr. Aliza Thompson Public – Private Partnerships/Collaborative Opportunities/An NIH View Dr. Barbara Mittleman Intellectual Property – An NIDDK View Ms. Anna Amar

9:00 – 9:30 a.m.	Break

9:30 – 12:00 p.m.	Ongoing Industry Trials/Research and Development Moderator: Dr. David Warnock Bardoxolone: BEACON Trial: Dr. Paul Audhya and Dr. Colin Meyer, Reatta Pharmaceuticals CTP-499, a First-in-Class Clinical Development Candidate for Diabetic Nephropathy Dr. James Shipley, CoNCERT Pharmaceuticals TBD Dr. Thomas Daniel, Celgene Corporation Atrasentan Dr. Dennis Andress, Abbott AST-120/EPPIC Program Dr. Alan Glicklich, Mitsubishi Tanabe Pharma America ALTITUDE Trial Dr. Marc Pfeffer Development of Acthar for Treatment of Diabetic Nephropathy Dr. David Young, Questcor Pharmaceuticals Industry Panel Discussion: Speaker Panel and Moderator

Noon – 3:00 p.m.	Breakout Sessions (Working Lunch) Continued from Day One Topics for Individual Breakout Sessions: Group 1 Trial in Children: Agent To Prevent Progression Moderators: Dr. Susan Furth, Dr. Russell Chesney, Dr. James Chan, Dr. Frederick Kaskel, Dr. Lynne Yao, and Dr. David Reboussin Group 2 Trial in Adults with Bicarbonate Moderators: Dr. Michal Melamed, Dr. Donald Wesson, and Dr. Tom Greene Group 3 Trial in Adults with Pentoxifylline Moderators: Dr. Robert Perkins and Dr. Linda Fried, NIH Biostatistician Group 4 Trial in Adults with Mineralocorticoid Receptor Blocker Moderators: Dr. Robert Toto, Dr. Tom Hostetter, and Dr. Michael Rosenblum Group 5 Trial in Adults with Phosphate Control/Vitamin D Moderators: Dr. Myles Wolf, Dr. Rajnish Mehrota, Dr. Ravi Thadani, and Dr. Glenn Chertow, NIH Biostatistician

3:00 – 5:00 p.m.	Reports From the Breakout Sessions: Discussion and Next Steps

5:00 – 5:15 p.m.	Summary Dr. Robert Star and Dr. Michael Flessner

5:15 p.m.	Adjournment