To Evaluate the Safety, Tolerability and Efficacy of R2R01 Combined With SOC as Compared to SOC Alone in Outpatients With Worsening Heart Failure (WHF)
NCT ID: NCT06264310
Last Updated: 2024-11-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
33 participants
INTERVENTIONAL
2024-03-01
2024-11-25
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
This study is a four-parallel-cohort study. All patients will be randomized to one of the following Cohorts:
1. Cohort 1 (N=8): Placebo once daily SC for 7 days.
2. Cohort 2 (N=8): 5.0 mg R2R01 once daily SC for 7 days.
3. Cohort 3 (N=8): 7.5 mg R2R01 once daily SC for 7 days.
4. 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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Placebo
8 study subjects will receive placebo once daily subcutaneous injection for 7 days.
Placebo
Matching placebo SC injection
5.0 mg R2R01
8 study subjects will receive 5.0 mg R2R01 once daily subcutaneous injection for 7 days.
R2R01
Pharmaceutical Form: sterile 2R vials containing 10 mg of R2R01 for SC injection.
7.5 mg R2R01
8 study subjects will receive 7.5 mg R2R01 once daily subcutaneous injection for 7 days.
R2R01
Pharmaceutical Form: sterile 2R vials containing 10 mg of R2R01 for SC injection.
10.0 mg R2R01
8 study subjects will receive 10.0 mg R2R01 once daily subcutaneous injection for 7 days.
R2R01
Pharmaceutical Form: sterile 2R vials containing 10 mg of R2R01 for SC injection.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Placebo
Matching placebo SC injection
R2R01
Pharmaceutical Form: sterile 2R vials containing 10 mg of R2R01 for SC injection.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. History of symptomatic HF (heart failure).
3. Male or female ≥ 18 years of age at screening.
4. Previous hospitalization for HF within the last 12 months prior to screening.
5. Patients on optimal background therapy as per local practice for at least 30 days prior to screening and tolerating this well.
6. Patients must present with at least 2 of the following signs / symptoms of
WHF congestion:
1. Dyspnea
2. Orthopnea
3. Fatigue
4. Jugular venous distension
5. Rales
6. Edema
7. 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.
8. Estimated Glomerular Filtration Rate (eGFR) between 20 and 75 mL/ min/1.73 m2 (calculated using the CKD-EPI equation) at screening.
9. NT-pro-BNP levels at screening:
1. ≥ 1000 pg/mL for patients with LVEF ≤ 40%
2. ≥ 700 pg/mL for patients with LVEF \> 40%
3. ≥ 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:
<!-- -->
1. ≥ 800 pg/mL for patients with LVEF ≤ 40%
2. ≥ 560 pg/mL for patients with LVEF \> 40%
3. ≥ 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.
10. Systolic Blood Pressure (SBP) ≥ 105 mmHg at screening.
11. Willing and able to stay in the clinic for observation/monitoring for 3 days.
12. Willing to self-administer all SC injections.
Exclusion Criteria
2. History of symptomatic hypotension.
3. History of orthostatic hypotension.
4. Temperature \> 38.5°C (oral or equivalent) or sepsis or active infection requiring antimicrobial treatment.
5. Clinical evidence of acute coronary syndrome (ACS) currently or within 30 days prior to Screening.
6. 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.
7. 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.
8. IV antimicrobial treatment for sepsis or active infection.
9. 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.
10. 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.
11. 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.
12. 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.
13. Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated.
14. Documented, prior to or at the time of screening, restrictive amyloid myocardiopathy, or acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy.
15. Any major solid organ transplant recipient or planned/ anticipated organ transplant within 1 year.
16. 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.
17. 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.
18. 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.
19. Use of other investigational drugs within 30 days prior to Screening.
20. History of known hypersensitivity/prior exposure to R2R01 or serelaxin.
21. 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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
International HealthCare, LLC
OTHER
River 2 Renal Corp.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Mayo Clinic
Phoenix, Arizona, United States
California Pacific Medical Center
San Francisco, California, United States
Mayo Clinic
Jacksonville, Florida, United States
Piedmont Hospital Transplant
Atlanta, Georgia, United States
Rush University Medical Center
Chicago, Illinois, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
University of Michigan Medical Center
Ann Arbor, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
VA North Texas Health Care
Dallas, Texas, United States
Baylor Scott and White All Saints Medical Center
Fort Worth, Texas, United States
University of Duisburg-Essen
Essen, North Rhine-Westphalia, Germany
University of Munster
Münster, North Rhine-Westphalia, Germany
University of Bologna
Bologna, , Italy
University-Hospital of Padova
Padua, , Italy
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
R2R01-WHF-201
Identifier Type: -
Identifier Source: org_study_id