A Phase 2, Multi-center, Randomized, Dose-Ranging, Placebo-Controlled, Double-blind Study of the Relaxin Agonist R2R01 in Patients at High Risk for Cardiac Surgery Associated - Acute Kidney Injury.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

River 2 Renal Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

10 Mar 2026 → ongoing

Decision date (initial)

2026-03-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

R2R

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the safety and efficacy of R2R01 for prevention of AKI (KDIGO definition) after cardiac surgery (CABG, valve surgery, aortic surgery, or a combination of the above) involving CPB, in subjects with additional risk factors for developing CSA-AKI.

Secondary objectives 6

1. To evaluate R2R01 for the reduction of postoperative AKI severity (KDIGO definition, see above)
2. To evaluate R2R01 for the reduction of postoperative AKI duration
3. To evaluate the efficacy of R2R01 on renal function
4. To evaluate R2R01 for the reduction of major adverse kidney events (MAKE) defined as all-cause mortality, RRT and/or ≥25% sustained reduction of kidney function compared to baseline, at postoperative Day 7, and at postoperative Day 30
5. To evaluate R2R01 for the length of postoperative stay in Intensive Care Unit (ICU) and overall hospitalization time
6. To evaluate R2R01 for the reduction of hospital readmissions at postoperative Day 30

Conditions and MedDRA coding

Patients at high risk for Cardiac Surgery Associated – Acute Kidney Injury (CSA-AKI) following coronary artery bypass graft (CABG), valve surgery, aortic surgery, or a combination of the above, involving cardiopulmonary bypass (CPB).

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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)
2. At least 18 years of age
3. Subject is scheduled for non-emergent CABG (single or multiple vessels), valve surgery (single or multiple valves), surgery of the ascending part of the aorta, or a combination of the above, involving cardiopulmonary bypass (CPB), AND risk factors for acute kidney injury (AKI) are present (at screening) as specified below: a. If only one type of surgery is scheduled, at least two AKI risk factors should be present b. If any combined surgery is scheduled, at least one AKI risk factor should be present. Risk factors for AKI: • Diabetes mellitus on pharmacological treatment • Confirmed diagnosis of hypertension • Documented history of Chronic Heart Failure with New York Heart Association (NYHA) class III or higher (see section 11.5 in Appendix) • Left ventricular ejection fraction (LVEF) ≤40% • Peripheral vascular disease defined as one or more of the following: claudication, carotid occlusion or >50% stenosis, amputation for arterial disease, previous or planned intervention on the abdominal aorta, limb arteries or carotids • Stroke/transient ischemic attack (TIA) defined as sudden onset of focal or global brain, spinal cord, or retinal vascular damage, resulting in symptoms and signs of acute nervous system defects, associated with cerebral circulation disorders • Documented atrial fibrillation (AF) on the ECG performed at the screening visit • Anemia with hemoglobin ≤11 g/dL at any time during the 3-month period before or at the time of screening • Body Mass Index (BMI) ≥ 30 kg/m2 • Age ≥70 years at the time of screening
4. Have stable renal function per Investigator assessment
5. Subject agrees not to participate in another interventional study after signing the ICF and until the end of study (EoS) visit has been completed

Exclusion criteria 22

1. Patient currently enrolled into another interventional clinical trial
2. Subject is scheduled for emergent surgery
3. Cardiac surgery planned to be performed "off-pump" without CPB
4. Expected CPB duration < 60 minutes
5. Body weight <50 kg; >120 kg
6. Presence of AKI (KDIGO criteria) at the time of randomization
7. Current, recent (within 4 weeks), or scheduled renal replacement therapy
8. Patients who are post-nephrectomy
9. Patients with CKD of equal or more than stage IV (GFR≤30 ml/min/1.73 m2)
10. Patient with a kidney transplant
11. Subject has a known or suspected glomerulonephritis at the time of randomization
12. Cardiogenic shock, hemodynamic instability, mechanical ventilation, intra-aortic balloon pump (IABP), left ventricular assist device (LVAD) or other forms of mechanical circulatory support (MCS), within 7 days prior to surgery
13. Patient received inotropes or vasopressors within 48 hours prior to the day of surgery
14. Known or suspected sepsis
15. Confirmed or suspected endocarditis
16. Other current active infection requiring antibiotic treatment
17. Patient has severe liver disease (Child-Pugh score >7 points)
18. Recently received (within the last 4 weeks) or is anticipated to receive before the end of the study chemotherapy which can interfere with kidney function (e.g. Platinum agents)
19. Patient previously enrolled and randomized into this study
20. 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
21. Known hypersensitivity to the study drug or any of its excipients
22. Any medical or social condition deemed by the investigator to be likely to interfere with a patient’s ability to give informed consent, cooperate, and participate in the study or to be likely to interfere with the interpretation of the results

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of subjects developing AKI within 7 days after start of on-pump cardiac surgery based on SCr (AKI of any stage according to KDIGO criteria, see above)
2. Nature, frequency and severity of treatment-emergent adverse events (TEAEs).

Secondary endpoints 8

1. Severity grade of AKI within 7 days after start of cardiac surgery based on SCr (according to KDIGO criteria, see above).
2. Duration of AKI defined as the number of days meeting the definition of AKI (according to KDIGO criteria, see above).
3. Change in SCr and cystatin C (and corresponding eGFR values) at postoperative hours 12, 24, 48, 72, and postoperative Days 7 and 30, versus baseline
4. Proportion of subjects with a major adverse kidney event (MAKE) defined as all-cause mortality, RRT and/or ≥ 25% sustained reduction of kidney function (i.e., a reduction of eGFR of 25% or more compared to the baseline pre-surgery sample, using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations (with either SCr, CyC, or both) at postoperative Day 7 and at postoperative Day 30
5. Length of ICU stay (in hours) defined as the duration of stay in the ICU immediately following surgery (or recovery room post-surgery) until ICU discharge
6. Length of Hospital stay (in days) defined as the duration of stay in the hospital from the day of surgery to hospital discharge
7. ICU free days and hospital free days
8. Proportion of subjects readmitted to the hospital at postoperative Day 30

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

River 2 Renal Corp.

Sponsor organisation

River 2 Renal Corp.

Address

7550 Purple Sage

City

Park City

Postcode

84098-5557

Country

United States

Scientific contact point

Organisation

River 2 Renal Corp.

Contact name

Chief Medical Officer

Public contact point

Organisation

River 2 Renal Corp.

Contact name

Chief Medical Officer

Third parties 1

Locations

2 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications