Trial Outcomes & Findings for Efficacy and Safety of RMC-035 in Subjects at High Risk for Acute Kidney Injury Following Open-Chest Cardiac Surgery (NCT NCT05126303)

NCT ID: NCT05126303

Last Updated: 2024-05-16

Results Overview

Percentage of subjects developing AKI based on Serum Creatinine and/or Urine Output per KDIGO definition

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

177 participants

Primary outcome timeframe

72 hours

Results posted on

2024-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	RMC-035 RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was based on renal function on 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	Placebo Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Overall Study STARTED	89	88
Overall Study COMPLETED	89	88
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of RMC-035 in Subjects at High Risk for Acute Kidney Injury Following Open-Chest Cardiac Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RMC-035 n=89 Participants 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	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion	Total n=177 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical >=65 years	70 Participants n=5 Participants	71 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	69 Participants n=7 Participants	139 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	82 Participants n=5 Participants	81 Participants n=7 Participants	163 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	86 Participants n=5 Participants	85 Participants n=7 Participants	171 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Canada	29 participants n=5 Participants	35 participants n=7 Participants	64 participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Czechia	12 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Germany	33 participants n=5 Participants	31 participants n=7 Participants	64 participants n=5 Participants
Region of Enrollment Spain	11 participants n=5 Participants	12 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: 72 hours

Population: All dosed

Percentage of subjects developing AKI based on Serum Creatinine and/or Urine Output per KDIGO definition

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria	50.6 percentage of subjects	39.8 percentage of subjects

SECONDARY outcome

Timeframe: 72 hours

Population: all dosed

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

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Area Under the Curve (AUC) of Serum Creatinine (SCr)	1.13 log(mg/dL)/day Interval 1.08 to 1.17	0.99 log(mg/dL)/day Interval 0.96 to 1.02

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

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

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Duration of AKI	1.5 Days Standard Deviation 2.6	1.1 Days Standard Deviation 3.04

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

SCr at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Change in SCr Values Over Time 12 hours	0.07 mg/dL Interval 0.04 to 0.11	-0.01 mg/dL Interval -0.05 to 0.02
Change in SCr Values Over Time 24 hours	0.11 mg/dL Interval 0.06 to 0.15	0.01 mg/dL Interval -0.04 to 0.05
Change in SCr Values Over Time 48 hours	0.08 mg/dL Interval 0.03 to 0.13	0.00 mg/dL Interval -0.04 to 0.05
Change in SCr Values Over Time 72 hours	0.05 mg/dL Interval 0.01 to 0.09	-0.03 mg/dL Interval -0.07 to 0.01
Change in SCr Values Over Time Day 7	0.04 mg/dL Interval 0.0 to 0.09	-0.02 mg/dL Interval -0.06 to 0.02
Change in SCr Values Over Time Day 30	-0.00 mg/dL Interval -0.04 to 0.04	0.01 mg/dL Interval -0.02 to 0.05
Change in SCr Values Over Time Day 90	-0.02 mg/dL Interval -0.06 to 0.02	0.03 mg/dL Interval -0.01 to 0.07

SECONDARY outcome

Timeframe: 7 days

Population: all dosed

Change from baseline of peak cystatin C from baseline to Day 7

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Peak Cystatin C Value	0.21 mg/L Interval 0.16 to 0.26	0.11 mg/L Interval 0.06 to 0.16

SECONDARY outcome

Timeframe: 72 hours

Population: all dosed

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

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
AUC of Cystatin C	1.21 log(mg/L)/day Standard Deviation 1.28	1.09 log(mg/L)/day Standard Deviation 1.31

SECONDARY outcome

Timeframe: 7 days

Population: all dosed

Renal replacement therapy (dialysis treatment) required by any participant for any reason

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Number of Participants Requiring Renal Replacement Therapy (Dialysis)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

Number of days that participants were not requiring dialysis

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Number of Days Without Need for Dialysis	90.0 Days Interval 90.0 to 90.0	90.0 Days Interval 90.0 to 90.0

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

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.

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Major Adverse Kidney Event (MAKE) - SCr Day 30	11.2 percentage of subjects	10.2 percentage of subjects
Major Adverse Kidney Event (MAKE) - SCr Day 90	6.7 percentage of subjects	15.9 percentage of subjects

SECONDARY outcome

Timeframe: 72 hours

Population: all dosed

AKI based on cystatin C and/or urine output (UO)

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
AKI Within 72 Hours Based on Cystatin C and UO	48.3 percentage of subjects	40.9 percentage of subjects

SECONDARY outcome

Timeframe: 7 days

Population: all dosed

AKI based on SCr and/or UO criteria, or cystatin C and/or UO criteria

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
AKI Within 7 Days	60.7 percentage of subjects	45.5 percentage of subjects

SECONDARY outcome

Timeframe: 7 days

Population: all dosed

AKI persistence, defined as an AKI (KDIGO definition) developing within 72 hours after first dose of IMP and with a duration of ≥72 hours

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Persistence of AKI	18.0 percentage of subjects	14.8 percentage of subjects

SECONDARY outcome

Timeframe: 7 days

Population: all dosed

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).

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Severity of AKI Stage 1	43.8 percentage of participants with AKI	53.8 percentage of participants with AKI
Severity of AKI Stage 2	50.0 percentage of participants with AKI	38.5 percentage of participants with AKI
Severity of AKI Stage 3	6.3 percentage of participants with AKI	7.7 percentage of participants with AKI

SECONDARY outcome

Timeframe: 90 days

Population: Data were not collected.

Post-baseline changes in UACR and UPCR at Day 4, Day 30, and Day 90

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 days

Population: all dosed

AUC(0-24) of RMC-035 concentrations in plasma (Day 3)

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Pharmacokinetics of RMC-035 (AUC)	14.63 h*ug/mL Standard Deviation 12.314	—

SECONDARY outcome

Timeframe: 7 days

Population: all dosed

Cmax of RMC-035 concentrations in plasma Day 3

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Pharmacokinetics of RMC-035 (Cmax) eGFR>=60	12.59 ug/mL Standard Deviation 25.046	—
Pharmacokinetics of RMC-035 (Cmax) eGFR<60	10.62 ug/mL Standard Deviation 3.989	—

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

Presence of ADA at Day 1 (pre-surgery), Day 30, and Day 90; positive samples

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Presence of Anti-drug Antibodies (ADA)	6 Participants	3 Participants

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

Characteristics of ADA developed at Day 30 and Day 90 with regards cross-reactivity with endogenous alpha-1-microglobulin (A1M)

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Characteristics of ADA (Cross-reactivity)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 7 days

Population: all dosed

Change from baseline of peak SCr from baseline to Day 7

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Peak SCr Value	0.27 mg/dL Interval 0.22 to 0.32	0.15 mg/dL Interval 0.1 to 0.2

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Major Adverse Kidney Event (MAKE) - Cystatin C Day 30	19.1 percentage of subjects	22.7 percentage of subjects
Major Adverse Kidney Event (MAKE) - Cystatin C Day 90	16.9 percentage of subjects	27.3 percentage of subjects

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Major Adverse Kidney Event (MAKE) - SCr and Cystatin C Day 30	14.6 percentage of subjects	13.6 percentage of subjects
Major Adverse Kidney Event (MAKE) - SCr and Cystatin C Day 90	11.2 percentage of subjects	22.7 percentage of subjects

SECONDARY outcome

Timeframe: 90 days

Population: all dosed

Cystatin C measurement in serum at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90

Outcome measures

Outcome measures
Measure	RMC-035 n=89 Participants RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 Participants Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Change in Serum Cystatin C Values Over Time 48 hours	0.04 mg/L Interval 0.0 to 0.09	-0.03 mg/L Interval -0.08 to 0.02
Change in Serum Cystatin C Values Over Time 12 hours	-0.15 mg/L Interval -0.19 to 0.11	-0.26 mg/L Interval -0.29 to -0.22
Change in Serum Cystatin C Values Over Time 24 hours	-0.04 mg/L Interval -0.09 to 0.0	-0.14 mg/L Interval -0.18 to -0.1
Change in Serum Cystatin C Values Over Time 72 hours	0.07 mg/L Interval 0.03 to 0.12	-0.00 mg/L Interval -0.05 to 0.04
Change in Serum Cystatin C Values Over Time Day 7	0.05 mg/L Interval -0.01 to 0.1	-0.01 mg/L Interval -0.06 to 0.04
Change in Serum Cystatin C Values Over Time Day 30	0.10 mg/L Interval 0.05 to 0.14	0.12 mg/L Interval 0.07 to 0.16
Change in Serum Cystatin C Values Over Time Day 90	0.10 mg/L Interval 0.05 to 0.16	0.14 mg/L Interval 0.08 to 0.19

Adverse Events

RMC-035

Serious events: 20 serious events

Other events: 75 other events

Deaths: 1 deaths

Placebo

Serious events: 15 serious events

Other events: 64 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Sara Thuresson, Head of Clinical Operations

Guard Therapeutics

Phone: +46733319438

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	RMC-035 n=89 participants at risk RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing was done per kg bodyweight and at Subjects with eGFR ≥60 mL/min/1.73m2 will receive 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 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours. RMC-035: Concentrate for Solution for Infusion	Placebo n=88 participants at risk Identical to RMC-035 arm except that the placebo contains no active ingredient. Placebo: Concentrate for Solution for Infusion
Cardiac disorders Atrial fibrillation	18.0% 16/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	28.4% 25/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Cardiac disorders Tachycardia	10.1% 9/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	0.00% 0/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Metabolism and nutrition disorders Hypervolaemia	10.1% 9/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	14.8% 13/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Metabolism and nutrition disorders Hyperglycaemia	6.7% 6/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	8.0% 7/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Metabolism and nutrition disorders Hypophosphataemia	5.6% 5/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	3.4% 3/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Metabolism and nutrition disorders Hypokalaemia	2.2% 2/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	5.7% 5/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
General disorders Chills	30.3% 27/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	2.3% 2/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
General disorders Oedema peripheral	9.0% 8/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	9.1% 8/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
General disorders Pyrexia	12.4% 11/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	2.3% 2/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Investigations Blood creatinine increased	6.7% 6/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	1.1% 1/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Investigations Haemoglobin decreased	5.6% 5/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	0.00% 0/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Blood and lymphatic system disorders Anaemia	19.1% 17/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	20.5% 18/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Blood and lymphatic system disorders Thrombocytopenia	14.6% 13/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	9.1% 8/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Blood and lymphatic system disorders Leukocytosis	7.9% 7/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	4.5% 4/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Respiratory, thoracic and mediastinal disorders Pleural effusion	10.1% 9/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	13.6% 12/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Respiratory, thoracic and mediastinal disorders Atelectasis	7.9% 7/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	8.0% 7/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Injury, poisoning and procedural complications Procedural pain	12.4% 11/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	10.2% 9/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Gastrointestinal disorders Nausea	21.3% 19/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	9.1% 8/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Gastrointestinal disorders Vomiting	6.7% 6/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	3.4% 3/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Vascular disorders Hypotension	11.2% 10/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	10.2% 9/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Vascular disorders Hypertension	9.0% 8/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	4.5% 4/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Renal and urinary disorders Acute kidney injury	12.4% 11/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	12.5% 11/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Psychiatric disorders Delirium	10.1% 9/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	4.5% 4/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.
Psychiatric disorders Confusional state	5.6% 5/89 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.	1.1% 1/88 • TEAEs (Treatment Emergent Adverse Events): 72 hours after last administration of study intervention, up to 90 days in total. For non-serious Adverse Events, TEAEs are presented, ie any AE that occurred after the initial IMP administration through 72 hours (inclusive) after the final IMP administration. For SAEs, all are presented as per standard definition.