Reducing the Impact of Chronic Kidney Disease (CKD): Opportunities for Randomized Clinical Trials

Event Details

Meeting Goals

1. Discuss critical elements of the study design to optimize the conduct and impact of Phase III clinical trials in CKD.
2. Identify interventions and therapies for CKD that are currently in clinical trials or are ready to be evaluated in clinical trials.
3. Discuss mechanisms for pathways of cooperation among industry, academia, government, and patient advocacy groups for CKD trials.

Agenda

July 19, 2011

7:00 a.m. - 8:00 a.m.

Registration

8:00 a.m. - 8:15 a.m.

Opening Remarks and Objectives
Dr. Robert Star and Dr. Michael Flessner

State-of-the-Art Lectures

Moderator: Dr. Glenn Chertow

8:15 a.m. - 9:45 a.m.

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 a.m. - 10:00 a.m.

Break

Challenges in Clinical Trial Design (I) � Planning Studies for CKD

Moderator: Dr. Laura Dember

10:00 a.m. - 12:30 p.m.

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 p.m. - 1:15 p.m.

Lunch (Pre-Purchased Box Lunches in Breakout Rooms)

Therapies in Phase II/Pilot Studies

Moderator: Dr. Flessner

1:15 p.m. - 3:40 p.m.

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

Breakout Sessions

Purpose: To discuss the critical design elements that are required to bring a medication or maneuver to a Phase III trial.

3:45 p.m. - 5:15 p.m.

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:

1. Define Trial Question: Preliminary Data?
2. Renal Endpoints for Phase III CKD Trial
   1. Proteinuria as an endpoint? Are there other surrogate endpoints?
   2. Creatinine (or cystatin C)-based endpoints: Doubling? Slope?
   3. Are CKD staging tools feasible endpoints?
   4. What are the obstacles that have prevented the design and execution of outcome studies for renal-specific endpoints?
3. Non-Renal Endpoints for Phase III CKD Trials
   1. Non-renal endpoints (CVD, mortality, hospitalization)
   2. Which should be used in either Phase II or Phase III studies?
   3. Should these be primary or secondary endpoints in Phase III studies?
4. Patient Selection and Recruitment
   1. Inclusion/exclusion criteria (Early disease vs. late disease)
   2. Impact of patient selection on design of study
   3. 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?
   4. Is the recruitment strategy feasible?
   5. Biomarkers for risk stratification
   6. Incorporation of Protocolized Adjunctive Care (Will this agent be added to ACEI or ARB or be substituted for the current standard of care?)
5. Adverse Events/Pilot and Feasibility Issues: Dose Selection
6. Sample Size and Power

5:15 p.m. - 6:00 p.m.

Preliminary Reports From the Breakout Sessions and General Discussion

6:00 p.m.

Adjournment

July 20, 2011

7:00 a.m. - 8:00 a.m.

Registration

Government-Academic-Industry Partnerships

Moderator: Dr. Michael Flessner

8:00 a.m. - 9:00 a.m.

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 a.m. - 9:30 a.m.

Break

Ongoing Industry Trials/Research and Development

Moderator: Dr. David Warnock

9:30 a.m. - 12:00 p.m.

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

Breakout Sessions (Working Lunch) Continued from Day One

Noon - 3:00 p.m.

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 p.m. - 5:00 p.m.

Reports From the Breakout Sessions: Discussion and Next Steps

5:00 p.m. - 5:15 p.m.

Summary
Dr. Robert Star and Dr. Michael Flessner

5:15 p.m.

Adjournment