Alcoholic Hepatitis Workshop FDA, NIAAA, AASLD Clinical Trial Endpoints for AH

March 26-27, 2018 

Food and Drug Administration
Great Room – White Oak Campus

10903 New Hampshire Ave., Silver Spring, MD


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Clinical Trial Design and Endpoints for Alcoholic Hepatitis (AH)
and other Alcohol-Associated Liver Diseases (AALD)

Link for watching the workshop remotely:

Lara Dimick-Santos
Svetlana Radaeva
Gyongyi Szabo 
Scientific Advisory Committee: 
Arun Sanyal
Mack Mitchell
Ramon Bataller
Craig McClain
Timothy Morgan
Michael Lucey
Donna Griebel
Dragos Roman
Lisa Soule
Stephanie O. Omokaro
Irene Tebbs
Bridget Williams-Simmons


Day 1  —  March 26th, 2018


 8:00 - 8:20 AM – Welcome and Opening Remarks

8:00 – 8:10 AM - Dragos Roman, Deputy Director Division of Gastroenterology and Inborn Errors Products, FDA

8:10 – 8:20 AM - Kathy Jung, Director, Division of Metabolism and Health Effects, NIAAA

Session 1: Overview of AALD and AH: What do we know? Where are the gaps?
Moderators: George Koob (NIAAA), Gyongyi Szabo
8:20 – 8:40 AM - Challenges in the field and recent developments from the EASL-AASLD AH conference – Gyongyi Szabo
8:40 – 9:00 AM - Patient perspective and how patient advocacy groups can work to support clinical trials –  Brian Bourgault, American Liver Foundation (ALF)
9:00 – 9:20 AM - How to address addiction and relapse? Medical treatment options for addiction and psychiatric care – Raye Litten, NIAAA
9:20 – 9:40 AM - Evaluation and management of alcohol use disorder in patients with AALD – Andrea DiMartini 
9:40 – 10:00 AM - The NIAAA alcohol treatment navigator – Lori Ducharme (NIAAA)
10:00 – 10:20 AM - Panel Discussion – Moderators (George Koob, Gyongyi Szabo) Raye Litten, Andrea DiMartini, Lori Ducharme (NIAAA), Brian Bourgault (American Liver Foundation [ALF]), Stephanie O. Omokaro (FDA),  Jonathan Martin (American Liver Foundation [ALF])
10:20 - 10:40 AM – BREAK
Session 2: Disease Definitions and Patient Populations of Interest for Potential Drug Development in AALD and AH
Moderators: Philippe Mathurin, Craig McClain
10:40 – 11:00 AM - AALD as a chronic and progressive disease that is stigmatized: AALD is a new name! – Mack Mitchell
11:00 – 11:20 AM - Standard definitions and common data elements for clinical trials in patients with AH: Recommendation from the NIAAA alcoholic hepatitis consortia – Suthat Liangpunsakul
11:20 – 11:40 AM - What is moderate AALD/AH and should we study it? How to define this population and would biomarkers be useful in defining the population for clinical trials? – Juan G-Abraldes
11:40 – 12:00 AM - What inclusion/exclusion criteria will define the different groups of patients (e.g., moderated acute AH, chronic cirrhosis, etc.)  in AALD; how do these criteria relate to disease definition? – Tim Morgan
12:00 – 12:20 AM  - What is the role of alcohol in acute on chronic liver disease? How to approach this in clinical trials? Should these subsets be stratified?  What other precipitating events result in acute on chronic liver failure? – Rajiv Jalan
12:20 AM – 12:45 PM - Panel Discussion – Moderators (Phillippe Mathurin, Craig McClain), Mack Mitchell,  Juan G-Abraldes, Suthat Liangpunsakul, Tim Morgan, Rajiv Jalan, Lara Dimick-Santos (FDA), Bin Gao (NIAAA), Kathy Jung (NIH), Shelia L Rieders (ALF)

12:45 - 1:45 PM – LUNCH


Session 3: Role of Liver Histopathology and Biomarkers in AALD and AH
Moderators: Suthat Liangpunsakul, David Kleiner (NIH) 
1:45 – 2:05 PM - What do we learn from liver biopsy? Correlation between clinical and histologic findings – Nitzan Roth
2:05 – 2:25 PM - Why is the practice different in different countries (logistics in US); addressing coagulopathy and obtaining results in adequate time. – Mack Mitchell
2:25 – 2:45 PM - Need for biopsy in clinical trials, UK viewpoint – Ewan Forrest (UK) 
2:45 – 3:05 PM - Need for biopsy in clinical trials, EU viewpoint – Alexandre Louvet
3:05 – 3:25 AM - Potential biomarkers that can be used to assess mechanisms of disease, disease severity, prognosis, and response to therapy through the course of alcoholic liver disease (liquid biopsy) -- Craig McClain
3:25 – 3:50 PM - Panel Discussion – Moderators (Naga Chalasani, David Kleiner), Nitzan Roth, Ewan Forrest, Alexandre Louvet, Craig McClain, Ruby Mehta (FDA), Chris Leptak (FDA), Shashi Amur (FDA), Svetlana Radaeva (NIAAA), Michael John Posivak (ALF) 

3:50 - 4:05 PM – BREAK


Session 4A: Clinical Trial Design and Endpoints in AALD and AH
Moderators: Lara Dimick-Santos, Arun Sanyal
4:05 – 4:25 PM – Possible regulatory pathways for clinical trials in different stages of AALD – Y. Veronica Pei
4:25 – 4:45 PM - How the investigational product’s mechanism of action can help optimize therapeutic development in severe AH: Lessons Learned from published AH trials – Philippe Mathurin
4:45 – 5:05 PM - Use of validated questionnaires and other instruments to monitor alcohol use in clinical trials – Daniel Falk, NIAAA 
5:05 – 5:30 PM - Panel Discussion – Moderators (Lara Dimick-Santos, Arun Sanyal), Y. Veronica Pei (FDA), Philippe Mathurin, Ashwani Singal, Daniel Falk (NIAAA), Jonathan Martin (ALF)


DAY 2 – March 27th, 2018

Session 4B: Clinical Trial Design and Endpoints in AALD and AH
Moderators: Anna Mae Diehl, Michael Lucey
8:00 – 8:20 AM - Designing clinical trials and endpoints for different stages of chronic and progressive AALD; PROs? – Arun Sanyal 
8:20 – 8:40 AM - How to select an adequate control (standard of care with corticosteroids or placebo?) – Ashwani Singal
8:40 – 9:00 AM - What can be leveraged from the existing experience in NASH drug development to inform biomarker and/or endpoints selection and adaptation – Dasarathy Srinivasan
9:00 – 9:25 AM - Panel Discussion – Moderators (Anna Mae Diehl, Michael Lucey), Philippe Mathurin, Arun Sanyal, Ashwani Singal, Dasarathy Srinivasan, Nikunj Patel (FDA), Daniel Falk (NIAAA), Michelle Campbell (FDA), Brian Bourgault (ALF)
9:25 - 9:45 AM – BREAK
Session 5: Approach to Safety and Supportive Care
Moderator: Patrick Kamath, Mack Mitchell
9:45 – 10:05 AM - Challenges to standardization of clinical management in relation to clinical trials (nutrition, renal function, general) – Michael Lucey
10:05 – 10:25 AM - How to define DILI in the setting of AALD and AH? Stopping rules. – Naga Chalasani
10:25 – 10:45 AM - DSMB talk, safety and challenges with patient management? – Anne Mae Diehl
10:45 – 11:05 AM - Causality attribution of other adverse events of special interests observed during clinical trials (drug vs. disease) – Vijay Shah 
11:05 AM – 11:25 AM - SIRS and mulitisystem organ failure in AH: Goals of treatment/outcomes and milestones – is it always survival in AH?  What are alternate outcomes? (e.g. avoidance of complications, transplantation, etc.,  improvement in QOL) – Patrick Kamath 
11:25 – 11:40 AM - Panel Discussion – Moderators (Patrick Kamath, Mack Mitchell), Michael Lucey, Naga Chalasani, Vijay Shah, Andrea DiMartini, Mark Avigan (FDA), Lorenzo Leggio (NIAAA), Mary Lee (NIAAA), Bridget Williams-Simmons (NIAAA), Shelia L Rieders (ALF)
11:40 AM - 12.30 PM – LUNCH
Session 6: Novel Therapies, Opportunities and Remaining Challenges
Moderator: Naga Chalasani, Vijay Shah
12:30 – 12:45 PM - Industry perspective, challenges with recruitment, evaluating serious adverse events and efficacy – Rob Myers (Gilead)
12:45 – 1:00 PM - Clinical trials of extracorporeal cell therapy in AH, lessons learned in recruitment and retention – Robert Ashley (Vital Therapies)
1:00 – 1:15 - DASH Consortium challenges with recruitment; lessons learned – Bruce Barton
1:15 – 1:30 PM - TREAT Consortium challenges with recruitment; lessons learned – Samer Gawrieh 
1:30 – 1:50 PM - Role of liver transplantation in clinical trials? How does transplant impact interpretation of data. Patient selection/exclusion criteria – Norah Terrault
1:50 – 2:10 PM - Data sharing and the Liver Forum experience – Veronica Miller
2:10 – 2:30 PM - What have we learned and next steps? – Gyongyi Szabo
2:30 – 3:00 PM - Panel Discussion – Moderators (Suthat Liangpunsakul, Vijay Shah),  Rob Myers, Robert Ashley, Veronica Miller, Samer Gawrieh, Bruce Barton, Norah Terrault, Gyongyi Szabo, Dragos Roman (FDA), Bin Gao (NIAAA), Kathy Jung (NIH), Tom Nealon (ALF)


Logistics Contact: Bridgette Green --