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

NCT05309200 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: OCE-205-201
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 23

Brief Summary

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.

Conditions

Cirrhosis; Ascites; Hepatorenal Syndrome; Acute Kidney Injury

Keywords

HRS-AKI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

Study Arms (5)

OCE-205 Cohort 1

PLACEBO COMPARATOR

Placebo, intravenous infusion

Drug: Placebo

OCE-205 Cohort 2

EXPERIMENTAL

OCE-205, 8 µg/hr, intravenous infusion

Drug: OCE-205

OCE-205 Cohort 3

EXPERIMENTAL

OCE-205, 15 µg/hr, intravenous infusion

Drug: OCE-205

OCE-205 Cohort 4

EXPERIMENTAL

OCE-205, 30 µg/hr, intravenous infusion

Drug: OCE-205

OCE-205 Cohort 5

EXPERIMENTAL

OCE-205, 50 µg/hr, intravenous infusion

Drug: OCE-205

Interventions

OCE-205 DRUG

The drug product, OCE-205, is a sterile solution to be used for intravenous infusion.

OCE-205 Cohort 2; OCE-205 Cohort 3; OCE-205 Cohort 4; OCE-205 Cohort 5

Placebo DRUG

Placebo to match OCE-205 is a sterile solution to be used for intravenous infusion.

OCE-205 Cohort 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ocelot Bio, Inc: lead

Study Sites (23)

Mayo Clinic - Phoenix

Phoenix, Arizona, 85054, United States

Location

Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

University of California, San Francisco Liver Clinic

San Francisco, California, 94143, United States

Location

Stanford Hospital

Stanford, California, 94305, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Tampa General Medical Group

Tampa, Florida, 33606, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Northwestern Medicine

Chicago, Illinois, 60611, United States

Location

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02144, United States

Location

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

New York-Presbyterian Hospital

New York, New York, 10065, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor University

Dallas, Texas, 75246, United States

Location

CHI St Luke's Health Baylor College of Medicine Medical Center

Houston, Texas, 77030, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Virginia Commonwealth University Health System

Richmond, Virginia, 23298, United States

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (11)

• 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.

  PMID: 25638527 BACKGROUND

• 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.

  PMID: 26896734 BACKGROUND

• 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.

  PMID: 25644760 BACKGROUND

• 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.

  PMID: 30213943 BACKGROUND

• 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.

  PMID: 18471512 BACKGROUND

• 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.

  PMID: 31700640 BACKGROUND

• 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.

  PMID: 24687396 BACKGROUND

• 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.

  PMID: 19201943 BACKGROUND

• 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.

  PMID: 18471513 BACKGROUND

• 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.

  PMID: 33657294 BACKGROUND

• 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.

  PMID: 26524479 BACKGROUND

MeSH Terms

Conditions

Fibrosis; Ascites; Hepatorenal Syndrome; Acute Kidney Injury

Interventions

OCE-205

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency

Study Officials

• Chief Medical Officer

  Ocelot Bio

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2022
• First Posted: April 4, 2022
• Study Start: April 28, 2022
• Primary Completion: September 12, 2023
• Study Completion: October 13, 2023
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (22)