Study to Evaluate R2R01 Plus Terlipressin Versus Terlipressin Alone in Patients With Hepatorenal Syndrome

Inclusion Criteria:

1. Patient is able to communicate well with the Investigator, understands and is willingto comply with all requirements of the study, and understands and signs the writteninformed consent form (ICF).
2. At least 18 years of age.
3. Cirrhosis and ascites.
4. AKI stage 2 or 3. AKI defined by any of the following: 1) increase in SCr (SCr) ≥ 0.3mg/dl (or ≥ 26.5 micromolar/L) within 48 h, or 2) increase ≥ 50% in baseline SCr,which is known or presumed to have occurred within the prior seven days.
5. QLY SCr ≥ to 1.5 mg/dl.
6. No sustained improvement in renal function (less than 20% decrease in SCr and SCr => 1.5 mg/dL) after 48 h of diuretic withdrawal and the beginning of plasma volumeexpansion with albumin.
7. Female patients as well as female partners of male patients must be willing to avoidpregnancy for the duration of the study (>90 days).

Exclusion Criteria:

1. Significant co-morbidities that in the opinion of the Investigator would precludestudy participation.
2. QLY SCr level > 5 mg/dL.
3. AKI stage 1.
4. ACLF stage 3.
5. Model for End-Stage Liver Disease (MELD) score >35.
6. At least one event of large volume paracentesis (LVP) > 4 Liters in the last 4 daysbefore enrollment.
7. Current or recent (within 4 weeks) treatment with nephrotoxic drugs (e.g.,aminoglycosides, amphotericin, cyclosporine, NSAIDS (e.g., ibuprofen, naproxen,celecoxib), significant exposure to radiographic contrast agents (large doses ormultiple injections of iodinated contrast media).
8. Shock (hypovolemic-, cardiogenic-, or vasodilatory/distributive shock) with meanarterial blood pressure (MAP) ≤70 mmHg or systolic blood pressure ≤90 mmHg along withhypoperfusion.
9. Sepsis or uncontrolled bacterial infection (e.g., persisting bacteremia, persistingascitic fluid leucocytosis, fever, increasing leucocytosis with vasomotor instability)as measured with the quick sepsis-related organ dysfunction assessment (qSOFA) score.
10. Fewer than two days of anti-infective therapy for documented or suspected infection.
11. Superimposed acute liver injury induced by drugs, herbal preparation or dietarysupplements, with the exception of alcoholic hepatitis.
12. Estimated life expectancy less than 5 days.
13. Hypoxia (<90%) or worsening respiratory symptoms.
14. Proteinuria > 500 mg/day.
15. Tubular epithelial casts, heme granular casts.
16. Haematuria or microhaematuria (more than 50 red blood cells per high power field).
17. Abnormal renal ultra-sonography unless there is a known chronic structural disease (e.g., diabetic or hypertensive nephropathy).
18. Current or recent (within 4 weeks) renal replacement therapy (RRT).
19. Severe cardiovascular and pulmonary diseases including, but not limited to, unstableangina, pulmonary edema, congestive heart failure requiring increasing doses of drugtherapy, persisting symptomatic peripheral vascular disease, or any othercardiovascular disease judged by the Investigator to be severe.
20. Transjugular intra-hepatic systemic shunt (TIPS) unless it is known to benon-functioning or occluded.
21. Ongoing use of vasopressors, unless used for only 48 h before screening; in this casea wash-out period of 8 h before enrollment will be necessary. Patients receivingmidodrine and octreotide may be enrolled but treatment must be discontinued prior toenrollment.
22. Known allergy or hypersensitivity to terlipressin or other component of the studytreatment.
23. Subject is not suitable to participate in the study for any reason (including, but notlimited to co-morbidities, history of non-compliance with study visits, procedures, ordrug administration) in the opinion of the Investigator.
24. Females of childbearing potential (those who are not surgically sterilized orpost-menopausal for at least 1 year) are excluded from participation in the studyunless they agree to use highly effective contraception.
25. Males who have no sterilization history and whose female partners have child-bearingpotential must agree to use a highly effective method of contraception during theperiod from the time of signing the informed consent form (ICF) through 90 days afterthe last dose of study drug. A male patient must agree to immediately inform theInvestigator if his partner becomes pregnant during the study.