Evaluation of RMC-035 Efficacy and Safety in Preventing Renal Dysfunction Post-Cardiac Surgery in High-Risk Patients: A Phase 2b Randomized, Placebo-Controlled Study
- Trial ID
- 2024-510658-28-00
- Protocol
- 24-ROS-07
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of RMC-035 compared to placebo on **renal function** at Day 90. This is clinically relevant as it aims to identify the optimal dose of RMC-035 for the protection of long-term renal function in patients undergoing cardiac surgery who are at high risk of kidney injury. The study addresses the critical need for effective interventions to prevent loss of renal function following cardiac surgery, which can significantly impact patient outcomes.
Secondary objectives include:
- Assessing the efficacy of RMC-035 (pooled low and high doses, and by each dose level) versus placebo on major adverse kidney events (MAKE) at Day 90.
- Evaluating the efficacy of each dose level of RMC-035 (low and high doses, respectively) versus placebo on renal function at Day 90.
Participants
The clinical trial involves a total of **56 participants** who are being evaluated for the efficacy of RMC-035 versus placebo on renal function at Day 90, specifically targeting individuals at high risk of kidney injury following cardiac surgery. The study population includes both **male and female subjects** aged between **18 and 85 years**. Participants were selected based on their scheduled non-emergent cardiac surgeries, such as CABG, valve, or ascending aorta aneurysm surgeries, and the presence of risk factors for acute kidney injury (AKI). These risk factors include a documented history of low left ventricular ejection fraction, previous cardiac surgeries, type 2 diabetes mellitus, age over 70, NYHA class II or higher, previous AKI, anemia, and albuminuria. The trial population is characterized by a diverse range of health statuses, with a focus on those with compromised renal function as indicated by an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m². Participants are required to adhere to specific lifestyle considerations, such as the use of effective contraception for women of childbearing potential and abstinence or condom use for male participants to prevent pregnancy during the study period. The trial does not include individuals who are pregnant, breastfeeding, or participating in another interventional study. The selection criteria ensure a focus on a vulnerable population at risk of renal complications post-cardiac surgery.
Plans and Procedures
The clinical trial is a **Phase 2b**, randomized, placebo-controlled, double-blind, parallel-group study designed to evaluate the efficacy and safety of **RMC-035** in participants at high risk for kidney injury following open-chest cardiac surgery. The primary objective is to assess the efficacy of RMC-035 compared to placebo on renal function at Day 90 and to determine the optimal dose for long-term renal protection. The trial is expected to commence recruitment on October 1, 2024, and conclude by November 30, 2025.
Participants will be randomly assigned to receive either RMC-035 or a placebo, with the intervention administered as an **infusion**. The study will include several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy, and a final end-of-study visit. The inclusion criteria require participants to be between 18 and 85 years old, with an estimated glomerular filtration rate (eGFR) of at least 30 ml/min/1.73m² at screening, and scheduled for specific types of non-emergent cardiac surgery. Participants must also present risk factors for kidney injury, such as a history of low left ventricular ejection fraction or type 2 diabetes mellitus.
The expected duration of participant involvement is approximately 90 days, with the primary endpoint being the change from baseline in eGFR based on serum creatinine at Day 90. Secondary endpoints include the occurrence of major adverse kidney events (MAKE) and changes in eGFR at Day 90. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The study is not classified as low intervention and is conducted under strict adherence to ethical guidelines and regulatory requirements.
Treatment
The clinical trial involves the administration of **RMC-035**, a biological entity developed by Guard Therapeutics International AB. RMC-035 is a recombinant protein, specifically a recombinant alpha-1-microglobulin, also known by its synonyms ROSgard and A1M-001. The pharmaceutical form of RMC-035 is an infusion, and it is administered as a concentrate for solution for infusion. The maximum daily dose is 120 mg, with a total maximum dose of 180 mg over a treatment period of up to 2 days. The administration route is intravenous infusion, and the dosing schedule is designed to optimize the protection of long-term renal function in patients undergoing cardiac surgery who are at high risk of kidney injury. Participant compliance with the dosing regimen will be monitored throughout the study to ensure adherence to the protocol.
The study also includes a **placebo** group to serve as a comparator for evaluating the efficacy and safety of RMC-035. The placebo is an aqueous clear, colorless to slightly yellow solution, which is administered in the same manner as the experimental treatment to maintain the double-blind nature of the trial. The placebo is designed to mimic the appearance and administration route of RMC-035, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This approach allows for an unbiased assessment of the treatment's effects on renal function at Day 90 post-surgery.
Efficacy
The efficacy of RMC-035 in the clinical trial will be assessed primarily by evaluating the **change from baseline in estimated Glomerular Filtration Rate (eGFR)** based on serum creatinine (SCr) at Day 90. This primary endpoint will be measured for pooled low and high dose levels. Secondary endpoints include the occurrence of Major Adverse Kidney Events (MAKE) and each MAKE component at Day 90, analyzed for pooled low and high doses, as well as by each dose level. Additionally, the change from baseline in eGFR based on SCr at Day 90 will be assessed separately for low and high doses.
The measurement and collection of these efficacy parameters will be conducted using validated laboratory tests to determine eGFR and SCr levels. The analysis will be performed at the specified timepoint of Day 90, ensuring a comprehensive evaluation of renal function over the course of the trial. The trial aims to identify the optimal dose of RMC-035 for the protection of long-term renal function in patients undergoing cardiac surgery who are at high risk of kidney injury.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age is ≥18 and <85 years at the time of signing the informed consent.
- eGFR is ≥30 ml/min/1.73m2 (at screening) using the CKD-EPI 2021 equation with SCr.
- Scheduled for non-emergent surgery of any or several of the following types with use of CPB: a. CABG surgery b. Valve surgery (single or multiple valves) c. Ascending aorta aneurysm surgery
- Risk factors for kidney injury are present (at screening) as specified below: a. eGFR is <60 mL/min/1.73m2 b. If eGFR is ≥60 mL/min/1.73m2 i. A combined surgery is scheduled AND at least one risk factor for kidney injury from list (1) to (8) below is present. ii. One type of surgery is scheduled AND at least two risk factors for kidney injury from list (1) to (8) below are present. Risk factors for AKI: (1) Documented history of LVEF <35% at any time during the 3-month period before or at the time of screening as assessed by either echocardiography, cardiac MRI or nuclear scan. (2) Repeat surgery/history of previous open chest cavity cardiac surgery with or without CPB. (3) Confirmed diagnosis of T2DM at least 3 months prior to screening AND ongoing treatment with an approved anti-diabetic drug. (4) Age ≥70 years at the time of screening. (5) Documented history of NYHA class II or higher at any time during the 3-month period before or at the time of screening (6) Documented history of AKI as per KDIGO criteria longer than 3 months before date of screening, independent of the etiology of AKI. (7) Documented history of anemia with hemoglobin ≤11 g/dL at any time during the 3-month period before or at the time of screening. (8) Documented history of albuminuria, defined as urine albumin-to-creatinine ratio (UACR) >100 mg/g in a spot urine sample or >100 mg/24 hour in a 24-hour urine collection at any time during the 3-month period before or at the time of screening.
- Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: - Is a WONCBP as defined in the protocol. - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency, as described in the protocol. A female participant is eligible to participate if she agrees not to donate ova during the study intervention period and for at least 7 days after the last dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (serum) within 48 hours before the first dose of study intervention. Additional requirements for pregnancy testing during and after study intervention are located in the protocol. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Male Participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 7 days after the last dose of study intervention: a. Refrain from donating fresh unwashed semen. b. And either (i) or (ii) below: i. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. ii. Must agree to use contraception/barrier as detailed below: - Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant. - Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.
- Capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Participant agrees not to participate in another interventional study from the time of signing the informed consent until the EOS visit.
Exclusion Criteria
- Any medical condition that in the opinion of the investigator makes the participant unsuitable for study participation. This includes participants unable to give their informed consent.
- Scheduled for emergent surgeries (eg, aortic dissection).
- Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries (eg, congenital heart defects). Scheduled additional left atrial appendage closure surgery or maze surgery is not an exclusion criterion.
- Scheduled to undergo TAVI or TAVR, or off-pump surgeries or LVAD implantation.
- Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices such as IABP within 24 hours prior to surgery.
- Requires any of the following within one week prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of MCS.
- Diagnosed with AKI (as defined by KDIGO criteria) within 3 months prior to surgery.
- Requires cardiopulmonary resuscitation within 14 days prior to cardiac surgery.
- Ongoing sepsis (as defined in the protocol) within the past 2 weeks or, in the opinion of the investigator, an untreated diagnosed clinically significant infection (viral or bacterial) prior to or at screening and before randomization.
- ALT or AST ≥3.0 x ULN.
- Total bilirubin ≥2.0 xULN (Participants with Gilbert’s syndrome can be included with total bilirubin ≥1.5 x ULN as long as direct bilirubin is < 1.5 x ULN).
- History of solid organ transplantation.
- History of Renal Replacement Therapy.
- Severe allergic asthma defined as confirmed diagnosis of asthma poorly controlled while receiving high-dose inhaled corticosteroid treatment, or with requirement of a high level of treatment to maintain control.
- Chronic immunosuppressive treatment that may have an impact on kidney function as assessed by the medical monitor.
- Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function as assessed by the medical monitor.
- Current enrolment or past participation within the last 90 days (or within 5 half-lives of an investigational study treatment, whichever is longer) before signing of consent in any other clinical study involving an investigational study treatment.
- Has previously received RMC-035.
- Hypersensitivity to any of the study interventions, or components thereof including excipients, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 01 Oct 2024 | 23 |
 Germany | Not Recruiting | 01 Oct 2024 | 53 |
 Spain | Not Recruiting | 01 Oct 2024 | 48 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
RMC-035 | Test | INFUSION | CONCENTRATE FOR SOLUTION FOR INFUSION | 120 | 2 | PRD11190007 |
An aqueous clear, colorless to slightly yellow solution. | Placebo | N/A | — | — | — | N/A |