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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Hepatorenal Syndrome, Acute Kidney Injury, Cirrhosis, Ascites

Intervention / Treatment
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* Drug: OCE-205
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HRS-AKI