To Evaluate the Safety, Tolerability and Efficacy of R2R01 Combined With SOC as Compared to SOC Alone in Outpatients With Worsening Heart Failure (WHF)

NCT06264310 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: R2R01-WHF-201
• Study Type: interventional
• Target: 33
• Locations: 3 countries
• Sites: 18

Brief 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)

Conditions

Heart Failure; Worsening Heart Failure (WHF)

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  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.

  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.

  Day 7, Day 30

• Number of patients requiring dose adjustment of oral diuretics during the 30-day follow-up.

  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.

  Day 30

• Number of cardiovascular hospitalizations among patients using descriptive and summary statistics for change from baseline by dose level at Day 30.

  Day 30

Study Arms (4)

Placebo

PLACEBO COMPARATOR

8 study subjects will receive placebo once daily subcutaneous injection for 7 days.

Drug: Placebo

5.0 mg R2R01

EXPERIMENTAL

8 study subjects will receive 5.0 mg R2R01 once daily subcutaneous injection for 7 days.

Drug: R2R01

7.5 mg R2R01

EXPERIMENTAL

8 study subjects will receive 7.5 mg R2R01 once daily subcutaneous injection for 7 days.

Drug: R2R01

10.0 mg R2R01

EXPERIMENTAL

8 study subjects will receive 10.0 mg R2R01 once daily subcutaneous injection for 7 days.

Drug: R2R01

Interventions

Placebo DRUG

Matching placebo SC injection

Placebo

R2R01 DRUG

Pharmaceutical Form: sterile 2R vials containing 10 mg of R2R01 for SC injection.

10.0 mg R2R01; 5.0 mg R2R01; 7.5 mg R2R01

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• River 2 Renal Corp.: lead
• International HealthCare, LLC: collaborator

Study Sites (18)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

California Pacific Medical Center

San Francisco, California, 94109, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Piedmont Hospital Transplant

Atlanta, Georgia, 30309, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

VA North Texas Health Care

Dallas, Texas, 75246, United States

Location

Baylor Scott and White All Saints Medical Center

Fort Worth, Texas, 76104, United States

Location

University of Duisburg-Essen

Essen, North Rhine-Westphalia, Germany

Location

University of Munster

Münster, North Rhine-Westphalia, Germany

Location

University of Bologna

Bologna, Italy

Location

University-Hospital of Padova

Padua, Italy

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Treatment of all cohorts will be double-blind (all patients, study staff, investigators and Sponsor). Site pharmacist is unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be randomly assigned to one of four cohorts. Three groups will receive R2R01, and one group will receive placebo.

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 16, 2024
• Study Start: March 1, 2024
• Primary Completion: November 4, 2024
• Study Completion: November 25, 2024
• Last Updated: November 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); DE (2); IT (2)