Notice of Intent to Publish: Alcohol-associated Hepatitis Clinical Network – Late Phase Clinical Trials

Key Dates

None

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) intends to issue limited competition Requests for Application (RFA) to support the continuation of the clinical research sites (funded through RFA-AA-18-002, https://grants.nih.gov/grants/guide/rfa-files/RFA-AA-18-002.html) and Data Coordinating Center (DCC, funded through RFA-AA-18-004, https://grants.nih.gov/grants/guide/rfa-files/RFA-AA-18-004.html) for the Alcohol-associated Hepatitis Network (AlcHepNet). The purpose of AlcHepNet is to improve biomedical, psychosocial and quality of life outcomes for patients with advanced alcohol-associated liver disease. 

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. 

The intended RFA is expected to be published in late December2023/ early January 2024, with an expected application due date in late February 2023/early March 2024.

The upcoming clinical sites RFA will run in parallel with a companion RFA that will solicit applications for a DCC. When reissued, the RFAs will continue to utilize the U01 and U24 grant mechanisms to support the clinical sites and DCC respectively.

 The AlcHepNet cooperative program will include participating clinical sites and the Data Coordinating Center. It will require a high level of coordination and sharing between investigators. By involvement as a cooperative agreement mechanism, it is expected that AlcHepNet program awardees will cooperate and coordinate their activities after awards are made by participating in Steering Committee meetings and in other activities.

The main focus of the network will be the conduct of an integrated treatment clinical trial that incorporates active treatment of Alcohol Use Disorder (AUD) with treatment of liver disease. Thus, collaborative studies combining expertise in hepatology and addiction medicine will be required and these investigators should begin to establish collaborations and plan applications.

The targeted patient population will include severe alcohol-associated hepatitis (sAH) and decompensated alcohol-associated cirrhosis (deAC).

Important gaps in knowledge and hurdles to care in patients with advanced ALD that could be addressed include but are not limited to:

• Effect of integrated treatments targeting both AUD and ALD on ALD patients’ survival.
• Potential drug-related hepatotoxicity of current AUD medications in patients with ALD.
• Lack of practical approaches (treatment duration, endpoints, outcome measures, etc.) to conduct clinical trials that combine AUD and ALD

To achieve the goals of the program, the RFAs will require that AlcHepNet will:

Conduct multi-center multi-disciplinary clinical trials designed to study safety and efficacy of interventions targeting both AUD and liver disease.Interventions to be studied include, but are not limited to, pharmacologic agents, behavioral, cognitive, and device-based approaches, or a combination thereof.

• Pharmacological agents can include repurposed drugs approved by the FDA for different conditions or investigational compounds that that have completed safety, pharmacokinetics and efficacy studies and are under mid- and late-stage development.
• The clinical RFA is not intended to support first-in-human clinical trials or clinical studies where the objective is to elucidate the pathogenesis of the disease or identify potential therapeutic targets for future clinical trial.
• Utilization of adaptive/SMART trial design and elements of hybrid decentralized trial may be incorporated with appropriate justification.

Provide open access of its data for the outside researchers.

Clinical Sites

All clinical sites will recruit and treat a sufficient number of participants, implement the protocol according to the manual of operations, collect the outcome data specified in the protocol and provide study data to the DCC.

Specific requirements for clinical site U01 applications:

• The collaborative clinical U01s must share identical specific aims, a specific protocol across the sites and be organized as such to increase sample size, accelerate recruitment, and increase sample diversity and representation.
• Each U01 needs to have 2 principal investigators, one representing hepatology and one representing addiction medicine.
• The program should provide a mechanism for cross-site coordination, quality control, database management, statistical analysis, and reporting in conjunction with the DCC.
• Each individual clinical site U01 application should provide a demonstrated track record in clinical trial enrollment and capacity to achieve milestones.

Data Coordinating Center

The DCC will continue to provide expert assistance on the coordination, administration, and support of all clinical research activities, biospecimen collection, and administrative support for the Steering Committee and its subcommittees.

Responsibilities of the DCC include the following:

• Provide full statistical support of initial design, implementation, final analysis, and publication
• Provide full data management support, data quality control, data monitoring, preparation of reports for the Data and Safety Monitoring Board (DSMB) and IND
• Maintain and continue the development of AlcHepNet Data Commons to enable the outside investigators to query and interact with the rich dataset being developed by the network.

Funding Information

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization
Eligible Agencies of the Federal Government

Applications are not being solicited at this time. 

Inquiries

Please direct all inquiries to:

Zhigang (Peter) Gao, MD.
Program Director
Division of Metabolism and Health Effects
National Institute on Alcohol Abuse and Alcoholism, NIH
6700B Rockledge Dr. RM 1235
Bethesda MD, 20892-6902
Tel: 301-443-6106
Fax: 301-594-0673
Email: [email protected]