Clinical trial NCT05309200: A Study of OCE-205 in Participants With Cirrhosis With Ascites Who Developed Hepatorenal Syndrome-Acute Kidney Injury
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cirrhosis
Ascites
Hepatorenal Syndrome
Acute Kidney Injury
Keywords: HRS-AKI
Lead sponsor: Ocelot Bio, Inc
Sponsor class: INDUSTRY
First posted: 2022-04-04
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to measurement of concentration serum creatinine (sCr) value of less than 1.5 mg/dL on 2 consecutive days
timeFrame: From Day 1 infusion start to Last Day of infusion end
Secondary outcomes:
measure: Mean Concentration of OCE-205 at Steady State Concentration (Css)
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Rate of Total Body Clearance (CL) of OCE-205
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Time to Elimination Half-Life (t1/2) of OCE-205
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Volume of Steady-State Volume of Distribution (Vss) of OCE-205
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Change in Mean Arterial Pressure (MAP) rate
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Percentage Change in rate of Mean Arterial Pressure (MAP)
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Change in Pulse Rate
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Percentage Change in Pulse Rate
timeFrame: From Day 1 infusion start to Last Day of infusion end
measure: Change in concentration of Serum Creatinine (sCr)
timeFrame: From Day 1 infusion start to Last Day of infusion end
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: Keck Medical Center of USC
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Liver Clinic
state: California
city: Stanford
country: United States
facility: Stanford Hospital
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: Tampa General Medical Group
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: New York-Presbyterian Hospital
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor University
state: Texas
city: Houston
country: United States
facility: CHI St Luke's Health Baylor College of Medicine Medical Center
state: Texas
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Ocelot Bio
name: Chief Medical Officer
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.