Heart FailurePhase 2NCT06264310
To Evaluate the Safety, Tolerability and Efficacy of R2R01 Combined With SOC as Compared to SOC Alone in Outpatients With Worsening Heart Failure (WHF)
A Phase 2 study testing R2R01 in people with Heart Failure and Worsening Heart Failure (WHF), run by River 2 Renal Corp. at 8 sites in United States.
Trial summary
This Study Aims to Evaluate the Safety, Tolerability and Efficacy of R2R01 Combined With SOC as Compared to SOC Alone in Outpatients With Worsening Heart Failure (WHF) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Worsening Heart Failure (WHF)
- What is being tested?
- R2R01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 8 sitesUnited States
- Study dates
- 1 Mar 2024to 25 Nov 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
- Able and willing to give written informed consent, and able to follow instructions and comply with follow-up procedures.
- History of symptomatic HF (heart failure).
- Male or female ≥ 18 years of age at screening.
- Previous hospitalization for HF within the last 12 months prior to screening.
- Patients on optimal background therapy as per local practice for at least 30 days prior to screening and tolerating this well.
- Patients must present with at least 2 of the following signs / symptoms of
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- WHF congestion:
- Dyspnea
- Orthopnea
- Fatigue
- Jugular venous distension
- Rales
- Edema
- Patient requires intensification (doubling the dose, adding another diuretic targeting another tubular segment) of oral diuretics, or IV diuresis for WHF as per Investigator at screening and treated as an outpatient patient.
- Estimated Glomerular Filtration Rate (eGFR) between 20 and 75 mL/ min/1.73 m2 (calculated using the CKD-EPI equation) at screening.
- NT-pro-BNP levels at screening:
- ≥ 1000 pg/mL for patients with LVEF ≤ 40%
- ≥ 700 pg/mL for patients with LVEF > 40%
- ≥ 1500 pg/mL for patients with current atrial fibrillation, regardless of LVEF. For patients with BMI ≥ 30 kg/m2 the NT-pro-BNP values are lowered by 20%. The values are as follows:
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- ≥ 800 pg/mL for patients with LVEF ≤ 40%
- ≥ 560 pg/mL for patients with LVEF > 40%
- ≥ 1200 pg/mL for patients with current atrial fibrillation, regardless of LVEF. The most recent LVEF value assessed in the 12 months prior to screening should be used.
- Systolic Blood Pressure (SBP) ≥ 105 mmHg at screening.
- Willing and able to stay in the clinic for observation/monitoring for 3 days.
- Willing to self-administer all SC injections.
Who cannot join
- Patients with blood pressure > 180 mmHg or persistent heart rate > 130 bpm at Screening.
- History of symptomatic hypotension.
- History of orthostatic hypotension.
- Temperature > 38.5°C (oral or equivalent) or sepsis or active infection requiring antimicrobial treatment.
- Clinical evidence of acute coronary syndrome (ACS) currently or within 30 days prior to Screening.
- Acute Heart Failure (AHF) due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate < 45 bpm or atrial fibrillation/flutter with sustained ventricular response of > 130 bpm.
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- The daily use of IV or oral steroids (including but not limited to the use of IV or oral steroids for respiratory disorders or COPD). Note, inhaled steroids are allowed.
- IV antimicrobial treatment for sepsis or active infection.
- Patients with severe renal impairment defined at Screening eGFR < 20 mL/min/1.73m2 (calculated using the CKD-EPI Equation), and/or those receiving current or planned dialysis or ultrafiltration.
- Patients with hemoglobin < 10 g/dL, or a history of blood transfusion within the 14 days prior to screening, or active life-threatening gastrointestinal bleeding.
- Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased ammonia levels, if performed) or history of cirrhosis with evidence of portal hypertension such as varices.
- Significant, uncorrected, left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area < 1.0 cm2 or mean gradient > 40 mmHg on echocardiogram), and/or severe mitral stenosis.
- Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated.
- Documented, prior to or at the time of screening, restrictive amyloid myocardiopathy, or acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy.
- Any major solid organ transplant recipient or planned/ anticipated organ transplant within 1 year.
- Major surgery, including implantable devices (e.g., implantable cardioverter defibrillator, cardiac resynchronization therapy), or major neurologic event including cerebrovascular events, within 30 days prior to screening.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past year with a current life expectancy less than 1 year due to the malignancy.
- Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestate, confirmed by a positive human chorionic gonadotropin laboratory test.
- Use of other investigational drugs within 30 days prior to Screening.
- History of known hypersensitivity/prior exposure to R2R01 or serelaxin.
- Any other medical condition(s) that might put the patient at risk or influence study results in the Investigator's opinion, or that the Investigator deems unsuitable for the study including drug or alcohol abuse or psychiatric, behavioral, or cognitive disorders sufficient to interfere with the patient's ability to understand and comply with the protocol instructions or follow-up procedures.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
J&S Studies
College Station, Texas, 77845
Lake Country
Eatonton, Georgia, 31024
Thomas Hospital
Fairhope, Alabama, 36532
C&R Research
Fort Meyers, Florida, 33919
C&R Research
Hialeah, Florida, 33013
Encore Clinical Research
Inverness, Florida, 34452
Encore Clinical Research
Jacksonville, Florida, 32216
Amavita Clinical Research
Miami, Florida, 33137
About this study
Official title: A Phase 2, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of the Relaxin Agonist R2R01 Combined With Standard of Care Versus Standard of Care Alone in Outpatients With Worsening Heart Failure (WHF)
This Study Aims to Evaluate the Safety, Tolerability and Efficacy of R2R01 Combined With SOC as Compared to SOC Alone in Outpatients With Worsening Heart Failure (WHF)
Read the detailed description
This is a Phase 2, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of the Relaxin Agonist R2R01 combined with Standard of Care versus Standard of Care Alone in Outpatients with Worsening Heart Failure (WHF). Each patient will undergo a screening period of up to 21 days, an active treatment period of 7 days, and a follow up period of 23 days after the last dose (30 days after the first dose), i.e., a total of up to 51 days total study duration.
This study is a four-parallel-cohort study. All patients will be randomized to one of the following Cohorts:
- Cohort 1 (N=8): Placebo once daily SC for 7 days.
- Cohort 2 (N=8): 5.0 mg R2R01 once daily SC for 7 days.
- Cohort 3 (N=8): 7.5 mg R2R01 once daily SC for 7 days.
- Cohort 4 (N=8): 10.0 mg R2R01 once daily SC for 7 days. All patients will present with worsening heart failure with congestion requiring SOC. The patient, in the opinion of the investigator, should be able to be treated for their symptoms without being admitted to the hospital. The planned 3-day hospitalization is to adequately manage any potential sign of hypotension and should not be required to treat the patient for the intensification of the diuretic therapy or same day IV loop diuretics. During the treatment period no new treatments for WHF should be initiated. This study will be conducted across approximately 8 centers in the US.
- Conditions
- Heart Failure, Worsening Heart Failure (WHF)
- Being tested
- Placebo, R2R01
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Matching placebo SC injection
R2R01Drug
Pharmaceutical Form: sterile 2R vials containing 10 mg of R2R01 for SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 8 study subjects will receive placebo once daily subcutaneous injection for 7 days. Receives: Drug: Placebo |
| 5.0 mg R2R01 | Experimental | 8 study subjects will receive 5.0 mg R2R01 once daily subcutaneous injection for 7 days. Receives: Drug: R2R01 |
| 7.5 mg R2R01 | Experimental | 8 study subjects will receive 7.5 mg R2R01 once daily subcutaneous injection for 7 days. Receives: Drug: R2R01 |
| 10.0 mg R2R01 | Experimental | 8 study subjects will receive 10.0 mg R2R01 once daily subcutaneous injection for 7 days. Receives: Drug: R2R01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and rate of patients with one or more TEAEs (treatment emergent AE's) and/or serious TEAEs as assessed by CTCAE v5.0.
To assess the safety and tolerability of various dose levels of R2R01 in WHF patients at Day 7 and Day 30.
Measured: Day 7, Day 30
Number and rate of patients with one or more TEAEs (treatment emergent AE's) and/or serious TEAEs as assessed by CTCAE v5.0.
To select the appropriate dose for Study R2R01-WHF-202
Measured: Day 30
Secondary outcomes (8)
Change from Baseline on NT-pro-BNP using descriptive and summary statistics by dose level at Day 7 and Day 30.
To evaluate the effect of R2R01 on NT-pro-BNP as a proxy for cardiac congestion at Day 7 and Day 30.
Measured: Day 7, Day 30
Change from baseline on Cystatin C and creatinine clearance using descriptive and summary statistics by dose level at Day 7 and Day 30.
To evaluate the effect of R2R01 on Cystatin C and creatinine clearance (eGFR using CKD-EPI Equation using both creatinine and cystatin C) at Day 7 and Day 30.
Measured: Day 7, Day 30
Number of patients requiring dose adjustment of oral diuretics during the 30-day follow-up.
To evaluate the effect of R2R01 on therapy with diuretics at Day 30.
Measured: Day 30
Number of patients with an event of: WHF-induced SDAC or other outpatient clinic visits requiring additional intensification of the therapy/IV loop diuretics using descriptive and summary statistics for change from baseline by dose level at Day 30.
To evaluate the effect of R2R01 at Day 30 on:
WHF-induced Same Day Access Clinic (SDAC)--or other outpatient clinic visits requiring, additional intensification of the therapy/IV loop diuretics.
Measured: Day 30
Number of cardiovascular hospitalizations among patients using descriptive and summary statistics for change from baseline by dose level at Day 30.
To evaluate the effect of R2R01 at Day 30 on: Cardiovascular (CV) hospitalizations.
Measured: Day 30
Number of all-cause hospitalizations among patients using descriptive and summary statistics for change from baseline by dose level at Day 30.
To evaluate the effect of R2R01 at Day 30 on: All-cause hospitalizations.
Measured: Day 30
Number of patients with CV mortality using descriptive and summary statistics for change from baseline by dose level at Day 30.
To evaluate the effect of R2R01 at Day 30 on: CV mortality.
Measured: Day 30
Number of patients with all-cause mortality using descriptive and summary statistics for change from baseline by dose level at Day 30.
To evaluate the effect of R2R01 at Day 30 on: All-cause mortality.
Measured: Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start1 Mar 2024
- Primary completion4 Nov 2024
- Study completion25 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Model description
- Patients will be randomly assigned to one of four cohorts. Three groups will receive R2R01, and one group will receive placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- River 2 Renal Corp.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- International HealthCare, LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06264310
- Sponsor's protocol ID
- R2R01-WHF-201
- Status last verified
- Jun 2026
- First submitted
- 31 Jan 2024
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of the Relaxin Agonist R2R01 Combined With Standard of Care Versus Standard of Care Alone in Outpatients With Worsening Heart Failure (WHF)
- ClinicalTrials.gov ID
- NCT06264310
- Acronym / sponsor ID
- R2R01-WHF-201
- Conditions
- Heart Failure, Worsening Heart Failure (WHF)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- River 2 Renal Corp.Industry (pharma, biotech, devices)
- Collaborators
- International HealthCare, LLC
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 4 Nov 2024 (actual)
- Study completion
- 25 Nov 2024 (actual)
- First posted
- 16 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Study Aims to Evaluate the Safety, Tolerability and Efficacy of R2R01 Combined With SOC as Compared to SOC Alone in Outpatients With Worsening Heart Failure (WHF)
Detailed description
This is a Phase 2, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of the Relaxin Agonist R2R01 combined with Standard of Care versus Standard of Care Alone in Outpatients with Worsening Heart Failure (WHF). Each patient will undergo a screening period of up to 21 days, an active treatment period of 7 days, and a follow up period of 23 days after the last dose (30 days after the first dose), i.e., a total of up to 51 days total study duration.
This study is a four-parallel-cohort study. All patients will be randomized to one of the following Cohorts:
- Cohort 1 (N=8): Placebo once daily SC for 7 days.
- Cohort 2 (N=8): 5.0 mg R2R01 once daily SC for 7 days.
- Cohort 3 (N=8): 7.5 mg R2R01 once daily SC for 7 days.
- Cohort 4 (N=8): 10.0 mg R2R01 once daily SC for 7 days. All patients will present with worsening heart failure with congestion requiring SOC. The patient, in the opinion of the investigator, should be able to be treated for their symptoms without being admitted to the hospital. The planned 3-day hospitalization is to adequately manage any potential sign of hypotension and should not be required to treat the patient for the intensification of the diuretic therapy or same day IV loop diuretics. During the treatment period no new treatments for WHF should be initiated. This study will be conducted across approximately 8 centers in the US.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Patients will be randomly assigned to one of four cohorts. Three groups will receive R2R01, and one group will receive placebo.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo8 study subjects will receive placebo once daily subcutaneous injection for 7 days. |
| 5.0 mg R2R01 | Experimental | Drug: R2R018 study subjects will receive 5.0 mg R2R01 once daily subcutaneous injection for 7 days. |
| 7.5 mg R2R01 | Experimental | Drug: R2R018 study subjects will receive 7.5 mg R2R01 once daily subcutaneous injection for 7 days. |
| 10.0 mg R2R01 | Experimental | Drug: R2R018 study subjects will receive 10.0 mg R2R01 once daily subcutaneous injection for 7 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Able and willing to give written informed consent, and able to follow instructions and comply with follow-up procedures.
- History of symptomatic HF (heart failure).
- Male or female ≥ 18 years of age at screening.
- Previous hospitalization for HF within the last 12 months prior to screening.
- Patients on optimal background therapy as per local practice for at least 30 days prior to screening and tolerating this well.
Key exclusion criteria (21 listed)
- Patients with blood pressure > 180 mmHg or persistent heart rate > 130 bpm at Screening.
- History of symptomatic hypotension.
- History of orthostatic hypotension.
- Temperature > 38.5°C (oral or equivalent) or sepsis or active infection requiring antimicrobial treatment.
- Clinical evidence of acute coronary syndrome (ACS) currently or within 30 days prior to Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboMatching placebo SC injection | Drug | Placebo |
| R2R01Pharmaceutical Form: sterile 2R vials containing 10 mg of R2R01 for SC injection. | Drug | 10.0 mg R2R01, 5.0 mg R2R01, 7.5 mg R2R01 |
Primary outcome
Number and rate of patients with one or more TEAEs (treatment emergent AE's) and/or serious TEAEs as assessed by CTCAE v5.0.
Time frame: Day 7, Day 30
To assess the safety and tolerability of various dose levels of R2R01 in WHF patients at Day 7 and Day 30.
Number and rate of patients with one or more TEAEs (treatment emergent AE's) and/or serious TEAEs as assessed by CTCAE v5.0.
Time frame: Day 30
To select the appropriate dose for Study R2R01-WHF-202
8 secondary outcomes
Change from Baseline on NT-pro-BNP using descriptive and summary statistics by dose level at Day 7 and Day 30.
Time frame: Day 7, Day 30
Change from baseline on Cystatin C and creatinine clearance using descriptive and summary statistics by dose level at Day 7 and Day 30.
Time frame: Day 7, Day 30
Number of patients requiring dose adjustment of oral diuretics during the 30-day follow-up.
Time frame: Day 30
Number of patients with an event of: WHF-induced SDAC or other outpatient clinic visits requiring additional intensification of the therapy/IV loop diuretics using descriptive and summary statistics for change from baseline by dose level at Day 30.
Time frame: Day 30
Number of cardiovascular hospitalizations among patients using descriptive and summary statistics for change from baseline by dose level at Day 30.
Time frame: Day 30
Number of all-cause hospitalizations among patients using descriptive and summary statistics for change from baseline by dose level at Day 30.
Time frame: Day 30
Number of patients with CV mortality using descriptive and summary statistics for change from baseline by dose level at Day 30.
Time frame: Day 30
Number of patients with all-cause mortality using descriptive and summary statistics for change from baseline by dose level at Day 30.
Time frame: Day 30
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing R2R01 in people with Heart Failure and Worsening Heart Failure (WHF), run by River 2 Renal Corp. at 8 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 26 inclusion and 21 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: finished, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and rate of patients with one or more TEAEs (treatment emergent AE's) and/or serious TEAEs as assessed by CTCAE v5.0. (time frame: Day 7, Day 30). The study lists 2 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 22 Jun 2026.