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

Acute Kidney Injury Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05309200
• Other study ID #: OCE-205-201
• Status: Completed
• Phase: Phase 2
• Start date: April 28, 2022
• Est. completion date: October 13, 2023

Study information

• Verified date: December 2023
• Source: Ocelot Bio, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: October 13, 2023
• Est. primary completion date: September 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Ascites
• Cirrhosis
• Fibrosis
• Hepatorenal Syndrome
• Liver Cirrhosis
• Syndrome
• Wounds and Injuries

Intervention

Drug:
• OCE-205
The drug product, OCE-205, is a sterile solution to be used for intravenous infusion.
• Placebo
Placebo to match OCE-205 is a sterile solution to be used for intravenous infusion.

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Medicine	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University of Missouri	Columbia	Missouri
United States	Baylor University	Dallas	Texas
United States	CHI St Luke's Health Baylor College of Medicine Medical Center	Houston	Texas
United States	Indiana University Hospital	Indianapolis	Indiana
United States	Keck Medical Center of USC	Los Angeles	California
United States	M Health Fairview University of Minnesota Medical Center	Minneapolis	Minnesota
United States	New York-Presbyterian Hospital	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Mayo Clinic - Phoenix	Phoenix	Arizona
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Virginia Commonwealth University Health System	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, San Francisco Liver Clinic	San Francisco	California
United States	Stanford Hospital	Stanford	California
United States	Tampa General Medical Group	Tampa	Florida
United States	MedStar Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Ocelot Bio, Inc

Countries where clinical trial is conducted

United States,  Canada, 

References & 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. Erratum In: J Hepatol. 2015 Jul;63(1):290. — View 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. — View 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. — View 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. Erratum In: Nat Rev Dis Primers. 2018 Oct 15;4(1):33. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

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