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Hepatorenal SyndromePhase 2NCT05875948

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

A Phase 2 study testing R2R01 and Terlipressin in people with Hepatorenal Syndrome and Acute Kidney Injury, run by River 2 Renal Corp. at 7 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study aims to evaluate the safety, tolerability and efficacy of R2R01 combined with terlipressin as compared to terlipressin alone in the treatment of patients with HRS-AKI Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatorenal Syndrome, Acute Kidney Injury
What is being tested?
R2R01 and Terlipressin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
95 participants
Where
7 sitesUnited States
Study dates
30 Jun 2023to Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient is able to communicate well with the Investigator, understands and is willing to comply with all requirements of the study, and understands and signs the written informed consent form (ICF).
  • At least 18 years of age.
  • Cirrhosis and ascites.
  • AKI stage 2 or 3. AKI defined by any of the following: 1) increase in SCr (SCr) ≥ 0.3 mg/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.
  • QLY SCr ≥ to 1.5 mg/dl.
  • 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 volume expansion with albumin.
  • Female patients as well as female partners of male patients must be willing to avoid pregnancy for the duration of the study (>90 days).

Who cannot join

  • Significant co-morbidities that in the opinion of the Investigator would preclude study participation.
  • QLY SCr level > 5 mg/dL.
  • AKI stage 1.
  • ACLF stage 3.
  • Model for End-Stage Liver Disease (MELD) score >35.
  • At least one event of large volume paracentesis (LVP) > 4 Liters in the last 4 days before enrollment.
Show all 25Show fewer
  • 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 or multiple injections of iodinated contrast media).
  • Shock (hypovolemic-, cardiogenic-, or vasodilatory/distributive shock) with mean arterial blood pressure (MAP) ≤70 mmHg or systolic blood pressure ≤90 mmHg along with hypoperfusion.
  • Sepsis or uncontrolled bacterial infection (e.g., persisting bacteremia, persisting ascitic fluid leucocytosis, fever, increasing leucocytosis with vasomotor instability) as measured with the quick sepsis-related organ dysfunction assessment (qSOFA) score.
  • Fewer than two days of anti-infective therapy for documented or suspected infection.
  • Superimposed acute liver injury induced by drugs, herbal preparation or dietary supplements, with the exception of alcoholic hepatitis.
  • Estimated life expectancy less than 5 days.
  • Hypoxia (<90%) or worsening respiratory symptoms.
  • Proteinuria > 500 mg/day.
  • Tubular epithelial casts, heme granular casts.
  • Haematuria or microhaematuria (more than 50 red blood cells per high power field).
  • Abnormal renal ultra-sonography unless there is a known chronic structural disease (e.g., diabetic or hypertensive nephropathy).
  • Current or recent (within 4 weeks) renal replacement therapy (RRT).
  • Severe cardiovascular and pulmonary diseases including, but not limited to, unstable angina, pulmonary edema, congestive heart failure requiring increasing doses of drug therapy, persisting symptomatic peripheral vascular disease, or any other cardiovascular disease judged by the Investigator to be severe.
  • Transjugular intra-hepatic systemic shunt (TIPS) unless it is known to be non-functioning or occluded.
  • Ongoing use of vasopressors, unless used for only 48 h before screening; in this case a wash-out period of 8 h before enrollment will be necessary. Patients receiving midodrine and octreotide may be enrolled but treatment must be discontinued prior to enrollment.
  • Known allergy or hypersensitivity to terlipressin or other component of the study treatment.
  • Subject is not suitable to participate in the study for any reason (including, but not limited to co-morbidities, history of non-compliance with study visits, procedures, or drug administration) in the opinion of the Investigator.
  • Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study unless they agree to use highly effective contraception.
  • Males who have no sterilization history and whose female partners have child-bearing potential must agree to use a highly effective method of contraception during the period from the time of signing the informed consent form (ICF) through 90 days after the last dose of study drug. A male patient must agree to immediately inform the Investigator if his partner becomes pregnant during the study.

Trial locations and contacts

7 sites in 1 country.

Guido Magni, MD, PHD contact

+41 794563810

magniguido@yahoo.com

Kathie Gabriel, RN, MFT contact

610-937-1932

kgabriel@narrowrivermgmt.com

7 sites in 1 country

United States7 sites, 7 recruiting
  • Piedmont Healthcare, Inc

    Atlanta, Georgia, 30309

    Recruiting
  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

    Not yet recruiting
  • Baylor Scott and White All Saints Medical Center

    Fort Worth, Texas, 76104

    Recruiting
  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

    Recruiting
  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Recruiting
  • Mayo Clinic

    Rochester, Minnesota, 55905

    Recruiting
  • California Pacific Medical Center

    San Francisco, California, 94114

    Not yet recruiting

Other trials in United States

About this study

Official title: A Single-blind, Phase 2, Multi-center, Randomized Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of the R2R01 Plus Terlipressin Versus Terlipressin Alone in Patients With Hepatorenal Syndrome - Acute Kidney Injury

This study aims to evaluate the safety, tolerability and efficacy of R2R01 combined with terlipressin as compared to terlipressin alone in the treatment of patients with HRS-AKI

Read the detailed description

This is a phase 2 randomized, single-blind, placebo-controlled, two group, multicenter trial preceded by a safety run-in, in patients with Hepatorenal Syndrome (HRS) - Acute Kidney Injury (HRS-AKI).

The study consists of:

  1. an Open-Label Safety Run-In Part with 3 Cohorts of patients, followed by
  2. a Single-Blind Placebo-Controlled Randomized Part with two Cohorts of patients treated in parallel, and
  3. an Open-Label Terlipressin Non-Responder Cohort.

All patients in all Cohorts will be treated with terlipressin, administered as a slow intravenous (IV) bolus 1 mg over 2 minutes every 6 hours (h) to be increased if clinically appropriate to 2.0 mg every 6 h. Terlipressin dosing should continue up to 24 h after achievement of an HRS response (either Partial or Full) based on Serum Creatinine (SCr)/AKI stage or up to day 14.

For those Cohorts where terlipressin will be administered combined with R2R01 (i.e., Cohorts 1, 2, 3, 4, and 6), the first R2R01 administration will commence immediately following the first terlipressin administration. Like terlipressin treatment, R2R01 dosing should continue up to 24 h after achievement of an HRS response (either Partial or Full) based on SCr/AKI stage or up to day 14.

All patients in all Cohorts will be followed for up to 90 days after the first dose of study drug.

This study will be conducted across approximately 25 centers in EU, UK, US, and Canada.

The screening period will occur within 14 days prior to the first dose administration.

The treatment duration is up to 14 days with a follow-up period of approximately 76 days.

The expected total duration of study participation is up to 15 weeks for each subject.

Being tested
R2R01, Terlipressin
Keywords
HRS-AKI, HRS, Renal Failure, Kidney Failure, Single-blind, Open-Label, Phase 2, R2R01
Medical subject headings
Hepatorenal Syndrome, Acute Kidney Injury, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • R2R01Drug

    Pharmaceutical form: sterile 2R vials containing 10 mg of R2R01.

  • TerlipressinDrug

    In the US, terlipressin is supplied as a sterile, preservative-free, lyophilized, white-to- off-white powder for intravenous (IV) administration. Each vial contains 0.85 mg Terlivaz, equivalent to 1 mg terlipressin acetate, and 10.0 mg mannitol. Terlivaz requires reconstituting in saline (5mL).

    In the EU, terlipressin is supplied in a clear glass vial with 5 ml of injection solution, containing 1 mg terlipressin acetate corresponding to 0.85 mg terlipressin.

Study groups in NCT05875948
Study groupRoleWhat they receive
An Open-Label Safety Run-In PartExperimentalThree 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.
Receives: Drug: R2R01; Drug: Terlipressin
Single-blind Placebo-controlled Randomized periodPlacebo comparatorAfter 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.
Receives: Drug: R2R01; Drug: Terlipressin
An Open-Label Terlipressin Non-Responder CohortExperimentalIn 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.
Receives: Drug: R2R01; Drug: Terlipressin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety Evaluation Criteria - Treatment Emergent Adverse Events (TEAEs)

    Safety and tolerability will be assessed by occurrence of TEAEs. Outcome will be reported as the count of participant experiencing TEAEs.

    Measured: From first dose of study drug to 30 days post last dose

  2. Safety Evaluation Criteria - Change in Weight

    Safety and tolerability will be assessed by change in body weight

    Measured: Change from screening through Day 30

  3. Safety Evaluation Criteria - Vital Signs - Respiration Rate

    Safety and tolerability will be assessed by change in respiration rate

    Measured: Change from screening through Day 30

  4. Safety Evaluation Criteria - Vital Signs - Body Temperature

    Safety and tolerability will be assessed by change in body temperature

    Measured: Change from screening through Day 30

  5. Safety Evaluation Criteria - Vital Signs - Continuous pulse oximetry (SpO2)

    Safety and tolerability will be assessed by change in SpO2

    Measured: Change from baseline through Day 30

  6. Safety Evaluation Criteria - Vital Signs - Systolic Blood Pressure (SBP)

    Safety and tolerability will be assessed by change in SBP

    Measured: Change from screening through Day 30

  7. Safety Evaluation Criteria - Vital Signs - Diastolic Blood pressure (DBP)

    Safety and tolerability will be assessed by change in DBP

    Measured: Change from screening through Day 30

  8. Safety Evaluation Criteria - Vital Signs - Heart Rate (HR)

    Safety and tolerability will be assessed by change in Heart Rate (HR)

    Measured: Change from screening through Day 30

  9. Safety Evaluation Criteria - ECGs - PR interval

    Safety and tolerability will be assessed by occurrence of ECGs

    Measured: Change from screening to Day 14 or hospital discharge

  10. Safety Evaluation Criteria - ECGs - RR interval

    Safety and tolerability will be assessed by occurrence of ECGs

    Measured: Change from screening to Day 14 or hospital discharge

  11. Safety Evaluation Criteria - ECGs - QRS duration

    Safety and tolerability will be assessed by occurrence of ECGs

    Measured: Change from screening to Day 14 or hospital discharge

  12. Safety Evaluation Criteria - ECGs - QT interval

    Safety and tolerability will be assessed by occurrence of ECGs

    Measured: Change from screening to Day 14 or hospital discharge

  13. Safety Evaluation Criteria - ECGs - QTcF interval

    Safety and tolerability will be assessed by occurrence of ECGs

    Measured: Change from screening to Day 14 or hospital discharge

  14. Safety Evaluation Criteria - ECGs - QTcB interval

    Safety and tolerability will be assessed by occurrence of ECGs

    Measured: Change from screening to Day 14 or hospital discharge

  15. The incidence of Responders

    The incidence of Responders (Established HRS reversal defined as patients with a Full or Partial HRS response (based on SCr/AKI stage) AND are alive without Renal Replacement Therapy (RRT) for at least 30 days after the first dose of study medication), evaluated separately as two different outcome groups and combined. In case of recurrence and retreatment during the first 30 days, the second treatment period will be evaluated for response

    Measured: 90 days

Secondary outcomes (2)
  1. Mortality Rate

    Number of patients who died at day 30, 60, and 90.

    Measured: 30, 60, 90 days

  2. Liver Transplant Rates

    Number of patients undergoing a liver transplant at day 30, 60, and 90.

    Measured: 30, 60, 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 May 2023
  2. Study start30 Jun 2023
  3. Primary completionDec 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
A. An Open-Label Safety Run-In Part with 3 Cohorts of patients, followed by B. A Single-Blind Placebo-Controlled Randomized Part with two Cohorts of patients treated in parallel, and C. An Open-Label Terlipressin Non-Responder Cohort.
Masking
Single blind
Who is masked
Participant
Enrolment
95 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05875948
Sponsor's protocol ID
R2R01-HRS-201
Status last verified
May 2023
First submitted
1 May 2023
Last updated
3 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing R2R01 and Terlipressin in people with Hepatorenal Syndrome and Acute Kidney Injury, run by River 2 Renal Corp. at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Guido Magni, MD, PHD (+41 794563810, magniguido@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Evaluation Criteria - Treatment Emergent Adverse Events (TEAEs) (time frame: From first dose of study drug to 30 days post last dose). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.

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