Efficacy and Safety of AXA1665 in Cirrhotic Subjects With Prior Overt Hepatic Encephalopathy (EMMPOWER)

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of AXA1665 in Subjects With Liver Cirrhosis and Prior Overt Hepatic Encephalopathy (EMMPOWER)

This is a global study to compare the effects of AXA1665, an orally active mixture of amino acids, compared to placebo, on cognitive and physical function, as well as the safety and tolerability of AXA1665.

Study Overview

• Status: Terminated
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: AXA1665; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ottawa, Canada
    • The Ottawa Hospital
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • Ontario
    • London, Ontario, Canada, N6A 2C2
      • LMC Diabetes & Endocrinology Ltd. - London
• Hungary
  • Debrecen, Hungary
    • Debreceni Egyetem Klinikai Kozpont
  • Székesfehérvár, Hungary
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
• Italy
  • Naples, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)
• Poland
  • Lublin, Poland
    • KO - MED Centra Kliniczne Lublin II
  • Mysłowice, Poland
    • ID Clinic
  • Szczecin, Poland
    • Sonomed Sp. z o.o.
  • Warszawa, Poland
    • Prywatna Specjalistyczna Praktyka Lekarska Jan Gietka
  • Wrocław, Poland
    • Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.
• Spain
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain
    • Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro
  • Santander, Spain
    • Hospital Universitario Marqués de Valdecilla
  • Santiago De Compostela, Spain
    • Hospital Clinico Universitario de Santiago
  • Sevilla, Spain
    • Hospital Universitario Virgen Del Rocio
• United Kingdom
  • Edinburgh, United Kingdom
    • The Royal Infirmary of Edinburgh
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco (UCSF)
  • Florida
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants
    • Gainesville, Florida, United States, 32610
      • UF Hepatology Research at CTRB
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33032
      • Homestead Associates in Research
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
    • New York, New York, United States, 10016
      • New York University (NYU) School of Medicine
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Cumberland Research Associates
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
  • Texas
    • Edinburg, Texas, United States, 78359
      • Optimed Research
    • Fort Worth, Texas, United States, 75246
      • Baylor Scott & White Research Institute
    • Houston, Texas, United States, 77030
      • Advanced Liver Therapies at St. Luke's Episcopal Hospital
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia School of Medicine
    • Newport News, Virginia, United States, 23602
      • Bon Secours Liver Institute
    • Richmond, Virginia, United States, 23114
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23249
      • McGuire Research Institute, Inc., McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing to participate in the study and provide written informed consent.
• Male and female adults aged ≥18 years.
• History of cirrhosis and at least 1 prior episode of overt hepatic encephalopathy (OHE) prior to Screening.
• A PHES of ≤ -4 during Screening.
• MELD score of ≤ 22 at Screening.
• Support of a primary caregiver who is able and willing to give written informed consent.

Exclusion Criteria:

• Hospitalization or serious medical condition.
• Presence of Child's-Pugh score ≥12, hepato-renal syndrome(s), refractory ascites, or spontaneous bacterial peritonitis (SBP).
• History of a surgical portosystemic or a transjugular intrahepatic portosystemic shunt (TIPS) placement.
• Expectation of a liver transplant during the study.
• Use of marijuana or tetrahydrocannabinol (THC) within 1 week prior to Screening and during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AXA1665 53.8 g per day; AXA1665 administered orally TID	Drug: AXA1665; AXA1665 administered TID with food
Placebo Comparator: Matching placebo; Placebo administered orally TID	Drug: Placebo; Matching placebo administered TID with food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in neurocognitive function by Psychometric Hepatic Encephalopathy Score (PHES)	Baseline to week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to and frequency of recurrent overt hepatic encephalopathy	Baseline to week 24
Impact on physical function assessed by Liver Frailty Index (a composite measure of hand grip strength, balance and ability to stand up from a chair)	Baseline to week 24
Incidence of study product emergent adverse events (AEs) and serious adverse events (SAEs)	Baseline to week 24

Collaborators and Investigators

• Sponsor: Axcella Health, Inc
• Investigators: Principal Investigator: Andres Duarte-Rojo, M.D., University of Pittsburgh

Publications and helpful links

Helpful Links

• EMMPOWER Phase 2 Clinical Trial Homepage

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: sarcopenia; liver cirrhosis; amino acids; end stage liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: AXA1665-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No