R2R01 + Terlipressin for Hepatorenal Syndrome

Recruiting at 7 trial locations

Overseen By Kathie Gabriel, RN, MFT

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: River 2 Renal Corp.

Must not be taking: Nephrotoxic drugs, NSAIDs

Disqualifiers: AKI stage 1, ACLF stage 3, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

95 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that patients stop taking certain medications, such as nephrotoxic drugs and vasopressors, before enrollment. If you are on midodrine or octreotide, you must discontinue them prior to joining the study.

What data supports the effectiveness of the drug R2R01 + Terlipressin for treating hepatorenal syndrome?

Research shows that terlipressin, when used with albumin, can improve kidney function in patients with hepatorenal syndrome, although its long-term survival benefits are unclear. Studies indicate that terlipressin is effective in reversing hepatorenal syndrome, especially when combined with liver transplantation, which significantly improves survival rates. ^{1 2 3 4 5}

Is the treatment with R2R01 + Terlipressin safe for humans?

Terlipressin has been used for many years to treat hepatorenal syndrome, but it can cause serious breathing problems in some people. It's important to monitor patients closely and choose those who are less likely to have these issues. ^{3 6 7 8 9}

How is the drug R2R01 + Terlipressin different from other treatments for hepatorenal syndrome?

The combination of R2R01 with Terlipressin is unique because Terlipressin is a vasoconstrictor (a drug that narrows blood vessels) commonly used to treat hepatorenal syndrome, but it is often expensive and not available everywhere. The addition of R2R01 may offer a novel approach, potentially enhancing the effectiveness or availability of treatment for this condition. ^{3 7 8 10 11}

What is the purpose of this trial?

This trial is testing a new drug called R2R01 combined with an existing drug, terlipressin, to treat patients with severe kidney problems related to liver disease (HRS-AKI). The goal is to see if this combination works better than using terlipressin alone. Terlipressin helps improve blood flow to the kidneys, and R2R01 might make this treatment even more effective. Terlipressin has been used for many years in Europe and has shown to be effective in improving kidney function.

Eligibility Criteria

Adults with cirrhosis, ascites, and severe kidney injury related to liver disease (HRS-AKI) can join this trial. They must understand the study and agree to its rules, including avoiding pregnancy. People with allergies to terlipressin or other serious health issues, recent infections without proper treatment, high MELD scores (>35), or those on certain medications are excluded.

Inclusion Criteria

I have cirrhosis and fluid buildup in my abdomen.

Your blood test shows a creatinine level higher than 1.5 mg/dl.

My kidney function hasn't improved despite treatment.

Exclusion Criteria

Doctors think you will live for less than 5 days.

You have more than 500 milligrams of protein in your urine every day.

You have blood in your urine or a high amount of red blood cells seen under a microscope.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Open-Label Safety Run-In

Three initial cohorts treated with an open-label combination of terlipressin and R2R01 to ascertain safety

14 days

Multiple visits as needed for safety assessment

Single-Blind Placebo-Controlled Randomized

Patients receive terlipressin and are randomized to either R2R01 or placebo

Up to 14 days

Regular visits for treatment administration and monitoring

Open-Label Terlipressin Non-Responder

Non-responders to terlipressin enter this cohort to receive R2R01

Up to 14 days

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

76 days

Periodic visits for safety and efficacy assessments

Treatment Details

Interventions

• R2R01
• Terlipressin

Trial Overview The trial is testing a combination of R2R01 and terlipressin against using just terlipressin for treating HRS-AKI. The goal is to see if adding R2R01 improves safety, tolerability, and effectiveness in patients compared to the standard treatment alone.

Participant Groups

Group I: An Open-Label Terlipressin Non-Responder Cohort Experimental Treatment 2 Interventions

In Cohort 5, if patients do not respond to terlipressin, they must discontinue Cohort 5. After discontinuation, they will be allowed to enter Cohort 6 (Terlipressin Non-Responder Part) to receive R2R01 with the same dosing and schedule as that for Cohort 4. No patient from any Cohort other than Cohort 5 will be allowed to enter Cohort 6.

Group II: An Open-Label Safety Run-In Part Experimental Treatment 2 Interventions

Three initial cohorts (Cohort 1, N=3 patients, Cohorts 2 and 3, N=6 patients, each) will be treated with an open-label combination of terlipressin and R2R01 to ascertain the safety of the combination therapy. A Safety Review Committee (SRC) will review the safety of Cohort 1 patients based on the adverse events and laboratory abnormalities up until Day 14, prior to the start of recruitment of Cohort 2 patients, as well as the safety of Cohorts 1 and 2 patients up until Day 14 prior to the start of recruitment of Cohort 3 patients. Data from all Cohorts 1, 2, and 3 patients up until Day 14 will be reviewed by the SRC before starting the randomized part of the study (Cohorts 4 and 5), so that the SRC can decide and confirm the most appropriate R2R01 dose schedule for patients in Cohorts 4 and 5. Patients enrolled in Cohorts 1, 2, or 3 will remain in their Cohort until study completion (Day 90) or study discontinuation.

Group III: Single-blind Placebo-controlled Randomized period Placebo Group 2 Interventions

After conclusion of the open-label safety run-in part, and after the SRC has determined the appropriate R2R01 dose schedule, approximately 80 patients will receive terlipressin and be randomized 1:1 to either R2R01 (Cohort 4) or placebo (Cohort 5). At randomization, patients will be stratified by the presence of systemic inflammatory response syndrome (SIRS), since patients with SIRS have shown a better response to terlipressin than patients without SIRS.

Who Is Running the Clinical Trial?

River 2 Renal Corp.

Lead Sponsor

Trials

2

Recruited

130+

References

1. China pubmed.ncbi.nlm.nih.gov

[A comparative study of high-or low-dose terlipressin therapy in patients with cirrhosis and type 1 hepatorenal syndrome]. [2018]

2. Pakistan pubmed.ncbi.nlm.nih.gov

Hepatorenal syndrome:Response to terlipressin and albumin and its determinants. [2020]

3. China pubmed.ncbi.nlm.nih.gov

[Meta-analysis of terlipressin in treatment of hepatorenal syndrome: an update]. [2018]

4. India pubmed.ncbi.nlm.nih.gov

Survival benefits of terlipressin and non-responder state in hepatorenal syndrome: a meta-analysis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Impact of liver transplantation on the survival of patients treated for hepatorenal syndrome type 1. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Respiratory events with terlipressin and albumin in hepatorenal syndrome: A review and clinical guidance. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Terlipressin in hepatorenal syndrome. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Noradrenaline vs terlipressin in the treatment of type 2 hepatorenal syndrome: a randomized pilot study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Terlipressin in the treatment of hepatorenal syndrome: A systematic review and meta-analysis. [2021]

10. Australia pubmed.ncbi.nlm.nih.gov

Terlipressin therapy for reversal of type 1 hepatorenal syndrome: a meta-analysis of randomized controlled trials. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. [2022]