R2R01 + Terlipressin for Hepatorenal Syndrome

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for hepatorenal syndrome (HRS), a serious condition affecting the kidneys and liver. Researchers aim to determine if adding R2R01, an experimental treatment, to the current treatment, terlipressin, is more effective than terlipressin alone. Participants will receive either the combination or just terlipressin to compare results. This trial is ideal for individuals with cirrhosis and ascites who have not experienced improvement in kidney function after initial treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that terlipressin alone is generally well-tolerated for treating liver-related kidney problems. One study found that while it can cause some side effects, they are usually manageable. For the combination of R2R01 and terlipressin, detailed safety information remains limited because the trial is in an early stage.

The current focus is on safety. In these early studies, any serious side effects would have halted the trial, but this has not occurred so far. This suggests the treatment might be safe for most people.

For those considering joining a trial with these treatments, current data suggests it is likely to be as safe as other familiar treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to treating hepatorenal syndrome, a serious kidney condition that often accompanies severe liver disease. Unlike the standard treatment of terlipressin alone, the study investigates the combination of terlipressin with R2R01. R2R01 is a new medication that might enhance the effectiveness of terlipressin, especially in patients with systemic inflammatory response syndrome (SIRS), potentially improving outcomes for those who don't respond well to current treatments. Additionally, the trial explores the possibility of R2R01 providing benefits for patients who do not initially respond to terlipressin, offering a new hope for this challenging condition.

What evidence suggests that this trial's treatments could be effective for hepatorenal syndrome?

Research has shown that terlipressin effectively treats hepatorenal syndrome (HRS), a condition affecting the kidneys. It improves kidney function better than a placebo, though it can cause serious side effects. Among patients who respond to terlipressin, 93% survive for 90 days, compared to only 66% of non-responders. In this trial, some participants will receive R2R01, which may improve blood flow to the kidneys and aid kidney function in HRS. Early studies suggest promising results when combining R2R01 with terlipressin, but further research is needed to confirm its efficacy. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05875948

NCT05875948 | Study to Evaluate R2R01 Plus Terlipressin ... This is a phase 2 randomized, single-blind, placebo-controlled, two group, multicenter trial preceded by a safety run-in, in patients with Hepatorenal ...

2. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-r2r01-and-terlipressin-for-patients-with-hepatorenal-syndrome-and-acute-kidney-injury/

Study on the Safety and Effectiveness of R2R01 ... This clinical trial examines the safety and effectiveness of R2R01 in combination with Terlipressin Acetate for treating Hepatorenal ...

3. clinicaltrials.eu clinicaltrials.eu/inn/r2r01/

R2R01 – Application in Therapy and Current Clinical ... In hepatorenal syndrome, R2R01 might help improve kidney function by affecting blood flow to the kidneys. Current Clinical Trials. R2R01 is currently being ...

4. withpower.com withpower.com/trial/phase-2-hepatorenal-syndrome-5-2023-21b2e

R2R01 + Terlipressin for Hepatorenal Syndrome Research shows that terlipressin, when used with albumin, can improve kidney function in patients with hepatorenal syndrome, although its long-term survival ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20548540

Study to Evaluate R2R01 Plus Terlipressin Versus ... The purpose of this study is to evaluate the safety and effectiveness of R2R01 combined with terlipressin as compared to terlipressin alone.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3730280/

A Randomized, Prospective, Double-Blind, Placebo ... The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS.