A Study of OCE-205 in Participants With Cirrhosis With Ascites Who Developed Hepatorenal Syndrome-Acute Kidney Injury

A Multi-Center, Randomized, Placebo-Controlled, Double-Blind, Adaptive Dose-Ranging Study to Assess Safety and Efficacy of Intravenous OCE-205 in Adults Diagnosed With Cirrhosis With Ascites Who Have Developed Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI)

OCE-205 is being tested to treat participants who have developed Hepatorenal Syndrome-Acute Kidney Injury as a complication of cirrhosis with ascites.

The study aims are to evaluate the safety and efficacy of OCE-205 at various doses.

Participants will receive treatment by intravenous infusion. Participants will continue with this treatment until participants meets primary endpoint or any discontinuation criteria.

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Ascites; Acute Kidney Injury; Hepatorenal Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: OCE-205

Detailed Description

The study will include 5 treatment arms including 1 Placebo Arm and 4 active drug arms. Participants will be randomly selected to 1 of 5 arms.

• Placebo
• OCE-205 at 8 micrograms per hour (µg/hr)
• OCE-205 at 15 micrograms per hour (µg/hr)
• OCE-205 at 30 micrograms per hour (µg/hr)
• OCE-205 at 50 micrograms per hour (µg/hr)

This multi-center trial will be conducted in the United States and Canada. If selected for the study, participants will be randomly assigned to 1 of the 5 treatment arms.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: 858-247-2267; Email: clinicaltrials@ocelotbio.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Phoenix
  • California
    • Los Angeles, California, United States, 90033
      • Keck Medical Center of USC
    • San Francisco, California, United States, 94143
      • University of California, San Francisco Liver Clinic
    • Stanford, California, United States, 94305
      • Stanford hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview University of Minnesota Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • New York
    • New York, New York, United States, 10065
      • New York-Presbyterian Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University
    • Houston, Texas, United States, 77030
      • CHI St Luke's Health Baylor College of Medicine Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent form (ICF) by participant or their legal/authorized representatives.
• Diagnosed with decompensated cirrhosis with ascites.
• Receiving albumin and has had appropriate diuretic withdrawal for at least 2 days prior to randomization into the study.
• Beta-blockers should be discontinued 48 hours prior to randomization, unless doctor deems necessary for appropriate medical treatment.
• No sustained improvement in renal function after both diuretic withdrawal and plasma volume expansion with albumin.
• Female participants must have a negative pregnancy test prior to randomization and agree to avoid becoming pregnant during the study and for 30 days after the end of treatment. Male participants must agree to use 2 effective contraceptive methods during the study and up to 30 days after the end of treatment.

Exclusion Criteria:

• Serum Creatinine >3.8 mg/dL.
• Large volume paracentesis (LVP ≥6L) within 4 days of randomization.
• Pulse oximeter reading of <90% on 2L or less.
• Sepsis and/or uncontrolled bacterial infection.
• Experienced shock within 72 hrs prior to screening.
• Model for End-Stage Liver Disease (MELD) score >35.
• Hypertension with a Systolic BP > 140 mmHg and/ or a Diastolic BP >100 mmHg.
• Treated with or exposed to nephrotoxic agents or has had exposure to radiographic contrast agents within 72 hrs prior to screening.
• Has superimposed acute liver injury due to drugs, or toxins except for acute alcoholic hepatitis.
• Proteinuria greater than 500 mg/dL.
• Impaired cardiac function as evidenced by symptoms consistent with New York Heart Association Classification Class 2 or worse.
• Received Renal Replacement Therapy (RRT) within 4 weeks of randomization.
• Has had a Trans Jugular Intrahepatic Porto-systemic shunt (TIPS).
• Pregnant or breastfeeding.
• Diagnosed with a malignancy within the past 5 years.
• History or current evidence of any condition (COVID-19 positive with respiratory/cardiac complications), therapy or laboratory abnormality that might confound the results of the study, interfere with the participation for the full duration of the study, or is not in the best interest to participate in the opinion of the investigator.
• Participated in a study of an investigational medical product or device within the last 8 weeks preceding screening.
• Experienced a major blood loss (≥500 mL) within the last 4 weeks prior to screening.
• Is stuporous or comatose at screening (West Haven scores III and IV). exhibiting bradycardia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: OCE-205 Cohort 1; Placebo, intravenous infusion	Drug: Placebo; Placebo to match OCE-205 is a sterile solution to be used for intravenous infusion.
Experimental: OCE-205 Cohort 2; OCE-205, 8 µg/hr, intravenous infusion	Drug: OCE-205; The drug product, OCE-205, is a sterile solution to be used for intravenous infusion.
Experimental: OCE-205 Cohort 3; OCE-205, 15 µg/hr, intravenous infusion	Drug: OCE-205; The drug product, OCE-205, is a sterile solution to be used for intravenous infusion.
Experimental: OCE-205 Cohort 4; OCE-205, 30 µg/hr, intravenous infusion	Drug: OCE-205; The drug product, OCE-205, is a sterile solution to be used for intravenous infusion.
Experimental: OCE-205 Cohort 5; OCE-205, 50 µg/hr, intravenous infusion	Drug: OCE-205; The drug product, OCE-205, is a sterile solution to be used for intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to measurement of concentration serum creatinine (sCr) value of less than 1.5 mg/dL on 2 consecutive days	From Day 1 infusion start to Last Day of infusion end

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Concentration of OCE-205 at Steady State Concentration (Css)	From Day 1 infusion start to Last Day of infusion end
Rate of Total Body Clearance (CL) of OCE-205	From Day 1 infusion start to Last Day of infusion end
Time to Elimination Half-Life (t1/2) of OCE-205	From Day 1 infusion start to Last Day of infusion end
Volume of Steady-State Volume of Distribution (Vss) of OCE-205	From Day 1 infusion start to Last Day of infusion end
Change in Mean Arterial Pressure (MAP) rate	From Day 1 infusion start to Last Day of infusion end
Percentage Change in rate of Mean Arterial Pressure (MAP)	From Day 1 infusion start to Last Day of infusion end
Change in Pulse Rate	From Day 1 infusion start to Last Day of infusion end
Percentage Change in Pulse Rate	From Day 1 infusion start to Last Day of infusion end
Change in concentration of Serum Creatinine (sCr)	From Day 1 infusion start to Last Day of infusion end

Collaborators and Investigators

• Sponsor: Ocelot Bio, Inc
• Investigators: Study Chair: Chief Medical Officer, Ocelot Bio

Publications and helpful links

General Publications

• Sanyal AJ, Boyer T, Garcia-Tsao G, Regenstein F, Rossaro L, Appenrodt B, Blei A, Gulberg V, Sigal S, Teuber P; Terlipressin Study Group. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008 May;134(5):1360-8. doi: 10.1053/j.gastro.2008.02.014. Epub 2008 Feb 13.
• Martin-Llahi M, Pepin MN, Guevara M, Diaz F, Torre A, Monescillo A, Soriano G, Terra C, Fabrega E, Arroyo V, Rodes J, Gines P; TAHRS Investigators. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008 May;134(5):1352-9. doi: 10.1053/j.gastro.2008.02.024. Epub 2008 Feb 14.
• Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, Moreau R, Jalan R, Sarin SK, Piano S, Moore K, Lee SS, Durand F, Salerno F, Caraceni P, Kim WR, Arroyo V, Garcia-Tsao G. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015 Apr;62(4):968-74. doi: 10.1016/j.jhep.2014.12.029. Epub 2015 Jan 28. No abstract available. Erratum In: J Hepatol. 2015 Jul;63(1):290.
• Boyer TD, Sanyal AJ, Wong F, Frederick RT, Lake JR, O'Leary JG, Ganger D, Jamil K, Pappas SC; REVERSE Study Investigators. Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1. Gastroenterology. 2016 Jun;150(7):1579-1589.e2. doi: 10.1053/j.gastro.2016.02.026. Epub 2016 Feb 16.
• Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P, Salerno F, Bernardi M, Romanelli RG, Colletta C, Salinas F, Di Giacomo A, Ridola L, Fornasiere E, Caraceni P, Morando F, Piano S, Gatta A, Angeli P; Italian Association for the Study of the Liver Study Group on Hepatorenal Syndrome. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology. 2015 Aug;62(2):567-74. doi: 10.1002/hep.27709. Epub 2015 Feb 13.
• Gines P, Sola E, Angeli P, Wong F, Nadim MK, Kamath PS. Hepatorenal syndrome. Nat Rev Dis Primers. 2018 Sep 13;4(1):23. doi: 10.1038/s41572-018-0022-7. Erratum In: Nat Rev Dis Primers. 2018 Oct 15;4(1):33.
• McClure T, Chapman B, Hey P, Testro A, Gow P. Long-term continuous terlipressin infusion in cirrhotic patients with hepatorenal syndrome or refractory ascites awaiting liver transplantation is associated with an increase in plasma sodium. United European Gastroenterol J. 2019 Nov;7(9):1271-1273. doi: 10.1177/2050640619878996. Epub 2019 Sep 19. No abstract available.
• Robertson M, Majumdar A, Garrett K, Rumler G, Gow P, Testro A. Continuous outpatient terlipressin infusion for hepatorenal syndrome as a bridge to successful liver transplantation. Hepatology. 2014 Dec;60(6):2125-6. doi: 10.1002/hep.27154. Epub 2014 May 19. No abstract available.
• Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Postgrad Med J. 2008 Dec;84(998):662-70. doi: 10.1136/gut.2006.107789.
• Wong F, Pappas SC, Curry MP, Reddy KR, Rubin RA, Porayko MK, Gonzalez SA, Mumtaz K, Lim N, Simonetto DA, Sharma P, Sanyal AJ, Mayo MJ, Frederick RT, Escalante S, Jamil K; CONFIRM Study Investigators. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med. 2021 Mar 4;384(9):818-828. doi: 10.1056/NEJMoa2008290.
• Vasudevan A, Ardalan Z, Gow P, Angus P, Testro A. Efficacy of outpatient continuous terlipressin infusions for hepatorenal syndrome. Hepatology. 2016 Jul;64(1):316-8. doi: 10.1002/hep.28325. Epub 2015 Dec 22. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): September 12, 2023
• Study Completion (Actual): October 13, 2023

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: HRS-AKI
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Liver Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Fibrosis; Syndrome; Wounds and Injuries; Liver Cirrhosis; Ascites; Acute Kidney Injury; Hepatorenal Syndrome
• Other Study ID Numbers: OCE-205-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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