Acute Kidney Injury
Conditions
Brief summary
This study evaluates RMC-035 compared to placebo for the prevention of acute kidney injury (AKI) in subjects who are at high risk for AKI following cardiac surgery. Half of the subjects will receive RMC-035 and the other half will receive placebo.
Detailed description
This is a Phase 2, randomized, double-blind, adaptive, parallel group clinical study that will evaluate RMC-035 compared to placebo in subjects at high risk for acute kidney injury (AKI) following cardiac surgery. Subjects are randomized in a 1:1 ratio.
Interventions
DRUGRMC-035
Concentrate for Solution for Infusion
DRUGPlacebo
Concentrate for Solution for Infusion
Sponsors
Guard Therapeutics AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-blind, adaptive, parallel group
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
1. Institutional Review Board/ International Ethics Committee approved Informed Consent obtained 2. Ability to understand and comply with the study requirements and able to provide written informed consent 3. Age ≥18 and \<85 years 4. Estimated glomerular filtration rate (eGFR) is ≥30 mL/min/1.73 m2 5. Subject is scheduled for non-emergent coronary artery bypass grafting (CABG) surgery and/or valve surgery and/or ascending aorta aneurysm surgery with use of cardiopulmonary bypass (CPB), and AKI risk factors are present at screening 6. Female subject is not of child-bearing potential, or agreeing not to become pregnant 7. Female subject must not be breastfeeding 8. Female subject must not donate ova 9. Male subject and their female spouse/partner(s) who are of childbearing potential must be using a highly effective form of birth control 10. Male subjects must not donate sperm 11. Subject agrees not to participate in another interventional study
Exclusion criteria
1. Medical condition that makes the subject unsuitable for study participation 2. Scheduled for emergent surgeries (eg, aortic dissection) 3. Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries (eg, congenital heart defects) 4. Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR), or off-pump surgeries or left ventricular assist device (LVAD) implantation 5. Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices within 24 hours prior to surgery 6. Requirement for defibrillator or permanent pacemaker, mechanical ventilation, intraaortic balloon pumping (IABP), LVAD, or other forms of mechanical circulatory support (MCS) 7. Diagnosed with AKI (as defined by KDIGO criteria) within 3 months prior to surgery 8. Required cardiopulmonary resuscitation within 14 days prior to cardiac surgery 9. Ongoing sepsis or an untreated diagnosed clinically significant infection (viral or bacterial) 10. Total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal (ULN) 11. History of solid organ transplantation 12. History of renal replacement therapy (RRT) 13. Medical condition which requires active immunosuppressive treatment 14. Severe allergic asthma 15. Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function 16. Received an investigational medicinal product within the last 90 days (or within 5 half-lives of the investigational drug, whichever is longer) 17. Subject has a known allergy to RMC-035 or one of its constituents, or has previously received RMC-035
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria | 72 hours | Percentage of subjects developing AKI based on Serum Creatinine and/or Urine Output per KDIGO definition |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of AKI | 90 days | Duration of AKI defined as the number of days meeting the definition of AKI (KDIGO definition) starting within 72 hours after first dose of IMP until resolution |
| Change in SCr Values Over Time | 90 days | SCr at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90 |
| Peak Cystatin C Value | 7 days | Change from baseline of peak cystatin C from baseline to Day 7 |
| AUC of Cystatin C | 72 hours | Time-corrected AUC of cystatin C for Day 1 to Day 4 (72 hours after first dose of IMP) calculated as follows: The area under the cystatin C concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed cystatin C values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x cystatin C(12h) + 0.5 x cystatin C(24h) + 1 x cystatin C(48h) + 1 x cystatin C(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3 |
| Number of Participants Requiring Renal Replacement Therapy (Dialysis) | 7 days | Renal replacement therapy (dialysis treatment) required by any participant for any reason |
| Number of Days Without Need for Dialysis | 90 days | Number of days that participants were not requiring dialysis |
| Major Adverse Kidney Event (MAKE) - SCr | 90 days | MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline. eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr. |
| AKI Within 72 Hours Based on Cystatin C and UO | 72 hours | AKI based on cystatin C and/or urine output (UO) |
| AKI Within 7 Days | 7 days | AKI based on SCr and/or UO criteria, or cystatin C and/or UO criteria |
| Persistence of AKI | 7 days | AKI persistence, defined as an AKI (KDIGO definition) developing within 72 hours after first dose of IMP and with a duration of ≥72 hours |
| Area Under the Curve (AUC) of Serum Creatinine (SCr) | 72 hours | Time-corrected area under the curve (AUC) of serum creatinine calculated as follows: The area under the SCr concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed SCr values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x SCr(12h) + 0.5 x SCr(24h) + 1 x SCr(48h) + 1 x SCr(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3 |
| Change in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) | 90 days | Post-baseline changes in UACR and UPCR at Day 4, Day 30, and Day 90 |
| Pharmacokinetics of RMC-035 (AUC) | 4 days | AUC(0-24) of RMC-035 concentrations in plasma (Day 3) |
| Pharmacokinetics of RMC-035 (Cmax) | 7 days | Cmax of RMC-035 concentrations in plasma Day 3 |
| Presence of Anti-drug Antibodies (ADA) | 90 days | Presence of ADA at Day 1 (pre-surgery), Day 30, and Day 90; positive samples |
| Characteristics of ADA (Cross-reactivity) | 90 days | Characteristics of ADA developed at Day 30 and Day 90 with regards cross-reactivity with endogenous alpha-1-microglobulin (A1M) |
| Peak SCr Value | 7 days | Change from baseline of peak SCr from baseline to Day 7 |
| Major Adverse Kidney Event (MAKE) - Cystatin C | 90 days | MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline. eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using Cystatin C. |
| Major Adverse Kidney Event (MAKE) - SCr and Cystatin C | 90 days | MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline. eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr and Cystatin C. |
| Change in Serum Cystatin C Values Over Time | 90 days | Cystatin C measurement in serum at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90 |
| Severity of AKI | 7 days | AKI severity stage 1, 2 or 3 per KDIGO criteria, with 1 being mildest stage and 3 being most severe stage. Reference: KDIGO (2012). Clinical Practice Guideline for Acute Kidney Injury. JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY 2(1). |
Countries
Canada, Czechia, Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RMC-035 RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration.
Dosing was based on renal function at Day -1: Subjects with eGFR ≥60 mL/min/1.73m2 received 1.3 mg/kg (per dose) for the first and second dose, followed by 0.65 mg/kg (per dose) for the third, fourth and fifth dose, while subjects with eGFR \>30 and \<60 mL/min/1.73m2 received 0.65 mg/kg (per dose) for all five doses Dosing occurred at time 0 and then after 6, 12, 24 and 48 hours.
RMC-035: Concentrate for Solution for Infusion | 89 |
| Placebo Identical to RMC-035 arm except that the placebo contains no active ingredient.
Placebo: Concentrate for Solution for Infusion | 88 |
| Total | 177 |
Baseline characteristics
| Characteristic | RMC-035 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 70 Participants | 71 Participants | 141 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 17 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 81 Participants | 163 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 86 Participants | 85 Participants | 171 Participants |
| Region of Enrollment Canada | 29 participants | 35 participants | 64 participants |
| Region of Enrollment Czechia | 12 participants | 8 participants | 20 participants |
| Region of Enrollment Germany | 33 participants | 31 participants | 64 participants |
| Region of Enrollment Spain | 11 participants | 12 participants | 23 participants |
| Region of Enrollment United States | 4 participants | 2 participants | 6 participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants | 38 Participants |
| Sex: Female, Male Male | 70 Participants | 69 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 89 | 2 / 88 |
| other Total, other adverse events | 75 / 89 | 64 / 88 |
| serious Total, serious adverse events | 20 / 89 | 15 / 88 |
Outcome results
Primary
Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria
Percentage of subjects developing AKI based on Serum Creatinine and/or Urine Output per KDIGO definition
Time frame: 72 hours
Population: All dosed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RMC-035 | Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria | 50.6 percentage of subjects |
| Placebo | Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria | 39.8 percentage of subjects |
Secondary
AKI Within 72 Hours Based on Cystatin C and UO
AKI based on cystatin C and/or urine output (UO)
Time frame: 72 hours
Population: all dosed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RMC-035 | AKI Within 72 Hours Based on Cystatin C and UO | 48.3 percentage of subjects |
| Placebo | AKI Within 72 Hours Based on Cystatin C and UO | 40.9 percentage of subjects |
Secondary
AKI Within 7 Days
AKI based on SCr and/or UO criteria, or cystatin C and/or UO criteria
Time frame: 7 days
Population: all dosed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RMC-035 | AKI Within 7 Days | 60.7 percentage of subjects |
| Placebo | AKI Within 7 Days | 45.5 percentage of subjects |
Secondary
Area Under the Curve (AUC) of Serum Creatinine (SCr)
Time-corrected area under the curve (AUC) of serum creatinine calculated as follows: The area under the SCr concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed SCr values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x SCr(12h) + 0.5 x SCr(24h) + 1 x SCr(48h) + 1 x SCr(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3
Time frame: 72 hours
Population: all dosed
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| RMC-035 | Area Under the Curve (AUC) of Serum Creatinine (SCr) | 1.13 log(mg/dL)/day |
| Placebo | Area Under the Curve (AUC) of Serum Creatinine (SCr) | 0.99 log(mg/dL)/day |
Secondary
AUC of Cystatin C
Time-corrected AUC of cystatin C for Day 1 to Day 4 (72 hours after first dose of IMP) calculated as follows: The area under the cystatin C concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed cystatin C values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x cystatin C(12h) + 0.5 x cystatin C(24h) + 1 x cystatin C(48h) + 1 x cystatin C(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3
Time frame: 72 hours
Population: all dosed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| RMC-035 | AUC of Cystatin C | 1.21 log(mg/L)/day | Standard Deviation 1.28 |
| Placebo | AUC of Cystatin C | 1.09 log(mg/L)/day | Standard Deviation 1.31 |
Secondary
Change in SCr Values Over Time
SCr at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90
Time frame: 90 days
Population: all dosed
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| RMC-035 | Change in SCr Values Over Time | 48 hours | 0.08 mg/dL |
| RMC-035 | Change in SCr Values Over Time | Day 7 | 0.04 mg/dL |
| RMC-035 | Change in SCr Values Over Time | 24 hours | 0.11 mg/dL |
| RMC-035 | Change in SCr Values Over Time | Day 30 | -0.00 mg/dL |
| RMC-035 | Change in SCr Values Over Time | 72 hours | 0.05 mg/dL |
| RMC-035 | Change in SCr Values Over Time | Day 90 | -0.02 mg/dL |
| RMC-035 | Change in SCr Values Over Time | 12 hours | 0.07 mg/dL |
| Placebo | Change in SCr Values Over Time | Day 90 | 0.03 mg/dL |
| Placebo | Change in SCr Values Over Time | 12 hours | -0.01 mg/dL |
| Placebo | Change in SCr Values Over Time | 24 hours | 0.01 mg/dL |
| Placebo | Change in SCr Values Over Time | 48 hours | 0.00 mg/dL |
| Placebo | Change in SCr Values Over Time | 72 hours | -0.03 mg/dL |
| Placebo | Change in SCr Values Over Time | Day 7 | -0.02 mg/dL |
| Placebo | Change in SCr Values Over Time | Day 30 | 0.01 mg/dL |
Secondary
Change in Serum Cystatin C Values Over Time
Cystatin C measurement in serum at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90
Time frame: 90 days
Population: all dosed
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| RMC-035 | Change in Serum Cystatin C Values Over Time | 24 hours | -0.04 mg/L |
| RMC-035 | Change in Serum Cystatin C Values Over Time | Day 7 | 0.05 mg/L |
| RMC-035 | Change in Serum Cystatin C Values Over Time | 48 hours | 0.04 mg/L |
| RMC-035 | Change in Serum Cystatin C Values Over Time | Day 30 | 0.10 mg/L |
| RMC-035 | Change in Serum Cystatin C Values Over Time | 12 hours | -0.15 mg/L |
| RMC-035 | Change in Serum Cystatin C Values Over Time | Day 90 | 0.10 mg/L |
| RMC-035 | Change in Serum Cystatin C Values Over Time | 72 hours | 0.07 mg/L |
| Placebo | Change in Serum Cystatin C Values Over Time | Day 90 | 0.14 mg/L |
| Placebo | Change in Serum Cystatin C Values Over Time | 24 hours | -0.14 mg/L |
| Placebo | Change in Serum Cystatin C Values Over Time | 48 hours | -0.03 mg/L |
| Placebo | Change in Serum Cystatin C Values Over Time | 72 hours | -0.00 mg/L |
| Placebo | Change in Serum Cystatin C Values Over Time | Day 7 | -0.01 mg/L |
| Placebo | Change in Serum Cystatin C Values Over Time | Day 30 | 0.12 mg/L |
| Placebo | Change in Serum Cystatin C Values Over Time | 12 hours | -0.26 mg/L |
Secondary
Change in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR)
Post-baseline changes in UACR and UPCR at Day 4, Day 30, and Day 90
Time frame: 90 days
Population: Data were not collected.
Secondary
Characteristics of ADA (Cross-reactivity)
Characteristics of ADA developed at Day 30 and Day 90 with regards cross-reactivity with endogenous alpha-1-microglobulin (A1M)
Time frame: 90 days
Population: all dosed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RMC-035 | Characteristics of ADA (Cross-reactivity) | 0 Participants |
| Placebo | Characteristics of ADA (Cross-reactivity) | 0 Participants |
Secondary
Duration of AKI
Duration of AKI defined as the number of days meeting the definition of AKI (KDIGO definition) starting within 72 hours after first dose of IMP until resolution
Time frame: 90 days
Population: all dosed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RMC-035 | Duration of AKI | 1.5 Days | Standard Deviation 2.6 |
| Placebo | Duration of AKI | 1.1 Days | Standard Deviation 3.04 |
Secondary
Major Adverse Kidney Event (MAKE) - Cystatin C
MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline. eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using Cystatin C.
Time frame: 90 days
Population: all dosed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RMC-035 | Major Adverse Kidney Event (MAKE) - Cystatin C | Day 30 | 19.1 percentage of subjects |
| RMC-035 | Major Adverse Kidney Event (MAKE) - Cystatin C | Day 90 | 16.9 percentage of subjects |
| Placebo | Major Adverse Kidney Event (MAKE) - Cystatin C | Day 30 | 22.7 percentage of subjects |
| Placebo | Major Adverse Kidney Event (MAKE) - Cystatin C | Day 90 | 27.3 percentage of subjects |
Secondary
Major Adverse Kidney Event (MAKE) - SCr
MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline. eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr.
Time frame: 90 days
Population: all dosed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RMC-035 | Major Adverse Kidney Event (MAKE) - SCr | Day 30 | 11.2 percentage of subjects |
| RMC-035 | Major Adverse Kidney Event (MAKE) - SCr | Day 90 | 6.7 percentage of subjects |
| Placebo | Major Adverse Kidney Event (MAKE) - SCr | Day 30 | 10.2 percentage of subjects |
| Placebo | Major Adverse Kidney Event (MAKE) - SCr | Day 90 | 15.9 percentage of subjects |
Secondary
Major Adverse Kidney Event (MAKE) - SCr and Cystatin C
MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline. eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr and Cystatin C.
Time frame: 90 days
Population: all dosed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RMC-035 | Major Adverse Kidney Event (MAKE) - SCr and Cystatin C | Day 30 | 14.6 percentage of subjects |
| RMC-035 | Major Adverse Kidney Event (MAKE) - SCr and Cystatin C | Day 90 | 11.2 percentage of subjects |
| Placebo | Major Adverse Kidney Event (MAKE) - SCr and Cystatin C | Day 30 | 13.6 percentage of subjects |
| Placebo | Major Adverse Kidney Event (MAKE) - SCr and Cystatin C | Day 90 | 22.7 percentage of subjects |
Secondary
Number of Days Without Need for Dialysis
Number of days that participants were not requiring dialysis
Time frame: 90 days
Population: all dosed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RMC-035 | Number of Days Without Need for Dialysis | 90.0 Days |
| Placebo | Number of Days Without Need for Dialysis | 90.0 Days |
Secondary
Number of Participants Requiring Renal Replacement Therapy (Dialysis)
Renal replacement therapy (dialysis treatment) required by any participant for any reason
Time frame: 7 days
Population: all dosed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RMC-035 | Number of Participants Requiring Renal Replacement Therapy (Dialysis) | 1 Participants |
| Placebo | Number of Participants Requiring Renal Replacement Therapy (Dialysis) | 1 Participants |
Secondary
Peak Cystatin C Value
Change from baseline of peak cystatin C from baseline to Day 7
Time frame: 7 days
Population: all dosed
| Arm | Measure | Value (MEAN) |
|---|---|---|
| RMC-035 | Peak Cystatin C Value | 0.21 mg/L |
| Placebo | Peak Cystatin C Value | 0.11 mg/L |
Secondary
Peak SCr Value
Change from baseline of peak SCr from baseline to Day 7
Time frame: 7 days
Population: all dosed
| Arm | Measure | Value (MEAN) |
|---|---|---|
| RMC-035 | Peak SCr Value | 0.27 mg/dL |
| Placebo | Peak SCr Value | 0.15 mg/dL |
Secondary
Persistence of AKI
AKI persistence, defined as an AKI (KDIGO definition) developing within 72 hours after first dose of IMP and with a duration of ≥72 hours
Time frame: 7 days
Population: all dosed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RMC-035 | Persistence of AKI | 18.0 percentage of subjects |
| Placebo | Persistence of AKI | 14.8 percentage of subjects |
Secondary
Pharmacokinetics of RMC-035 (AUC)
AUC(0-24) of RMC-035 concentrations in plasma (Day 3)
Time frame: 4 days
Population: all dosed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RMC-035 | Pharmacokinetics of RMC-035 (AUC) | 14.63 h*ug/mL | Standard Deviation 12.314 |
Secondary
Pharmacokinetics of RMC-035 (Cmax)
Cmax of RMC-035 concentrations in plasma Day 3
Time frame: 7 days
Population: all dosed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RMC-035 | Pharmacokinetics of RMC-035 (Cmax) | eGFR>=60 | 12.59 ug/mL | Standard Deviation 25.046 |
| RMC-035 | Pharmacokinetics of RMC-035 (Cmax) | eGFR<60 | 10.62 ug/mL | Standard Deviation 3.989 |
Secondary
Presence of Anti-drug Antibodies (ADA)
Presence of ADA at Day 1 (pre-surgery), Day 30, and Day 90; positive samples
Time frame: 90 days
Population: all dosed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RMC-035 | Presence of Anti-drug Antibodies (ADA) | 6 Participants |
| Placebo | Presence of Anti-drug Antibodies (ADA) | 3 Participants |
Secondary
Severity of AKI
AKI severity stage 1, 2 or 3 per KDIGO criteria, with 1 being mildest stage and 3 being most severe stage. Reference: KDIGO (2012). Clinical Practice Guideline for Acute Kidney Injury. JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY 2(1).
Time frame: 7 days
Population: all dosed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RMC-035 | Severity of AKI | Stage 1 | 43.8 percentage of participants with AKI |
| RMC-035 | Severity of AKI | Stage 2 | 50.0 percentage of participants with AKI |
| RMC-035 | Severity of AKI | Stage 3 | 6.3 percentage of participants with AKI |
| Placebo | Severity of AKI | Stage 1 | 53.8 percentage of participants with AKI |
| Placebo | Severity of AKI | Stage 2 | 38.5 percentage of participants with AKI |
| Placebo | Severity of AKI | Stage 3 | 7.7 percentage of participants with AKI |