Trial Outcomes & Findings for Vascular Endothelial Growth Factor-B (VEGF-B) Blockade With the Monoclonal Antibody CSL346 in Subjects With Diabetic Kidney Disease (NCT NCT04419467)

Results Overview

Data are presented as the geometric mean (GM) of percent change, which is calculated as the geometric mean of the Week 16 ACR to baseline, expressed as percent change from baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Baseline up to Week 16

Results posted on

2023-12-06

Participant Flow

Participants were enrolled at study centers in Australia, Canada, Israel, New Zealand, Puerto Rico and the United States.

A total of 327 participants were screened, of which 114 participants met the eligibility criteria, completed the Lead-in Period and were randomized to receive CSL346 (low dose), CSL346 (high dose), or Placebo.

Participant milestones

Participant milestones
Measure	CSL346 (Low Dose) Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline
Overall Study STARTED	29	29	56
Overall Study COMPLETED	27	26	47
Overall Study NOT COMPLETED	2	3	9

Reasons for withdrawal

Reasons for withdrawal
Measure	CSL346 (Low Dose) Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline
Overall Study Not treated with IP	0	0	2
Overall Study Adverse Event	0	2	0
Overall Study Death	1	0	0
Overall Study Lost to Follow-up	0	1	2
Overall Study Withdrawal by Subject	0	0	4
Overall Study Pandemic related	0	0	1
Overall Study Reason not known	1	0	0

Baseline Characteristics

Vascular Endothelial Growth Factor-B (VEGF-B) Blockade With the Monoclonal Antibody CSL346 in Subjects With Diabetic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=56 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	Total n=114 Participants Total of all reporting groups
Age, Continuous	62.0 Years n=5 Participants	61.0 Years n=7 Participants	63.0 Years n=5 Participants	62.0 Years n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	28 Participants n=4 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants	86 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants	36 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	20 Participants n=7 Participants	37 Participants n=5 Participants	78 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants	19 Participants n=7 Participants	35 Participants n=5 Participants	72 Participants n=4 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment New Zealand	8 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants	23 participants n=4 Participants
Region of Enrollment Canada	0 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants
Region of Enrollment Puerto Rico	3 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment United States	14 participants n=5 Participants	18 participants n=7 Participants	32 participants n=5 Participants	64 participants n=4 Participants
Region of Enrollment Israel	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Australia	3 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	13 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 16

Population: Intent to Treat Analysis Set

Data are presented as the geometric mean (GM) of percent change, which is calculated as the geometric mean of the Week 16 ACR to baseline, expressed as percent change from baseline.

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=28 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=27 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=48 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR)	3.2 Geometric Mean of Percent Change Interval -9.79 to 18.05	17.7 Geometric Mean of Percent Change Interval 2.54 to 35.18	5.4 Geometric Mean of Percent Change Interval -3.24 to 14.91	—	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=54 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	22 Participants	23 Participants	32 Participants	—	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=54 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Percentage of Subjects With TEAEs	75.9 Percentage of participants	79.3 Percentage of participants	59.3 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety Analysis Set

Data are presented for treatment-emergent AESIs.

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=54 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Number of Subjects With Adverse Events of Special Interest (AESIs)	10 Participants	6 Participants	13 Participants	—	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety Analysis Set

Data are presented for treatment-emergent AESIs.

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=54 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Percentage of Subjects With AESIs	34.5 Percentage of participants	20.7 Percentage of participants	24.1 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Baseline up to 24 weeks

Population: Intent-to-Treat Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=29 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Observed Value and Mean Change From Baseline in Serum Creatinine Baseline	1.273 mg/dL Standard Deviation 0.5502	—	1.321 mg/dL Standard Deviation 0.5592	—	1.207 mg/dL Standard Deviation 0.5184	—
Observed Value and Mean Change From Baseline in Serum Creatinine Day 8	1.306 mg/dL Standard Deviation 0.5374	0.032 mg/dL Standard Deviation 0.1900	1.269 mg/dL Standard Deviation 0.5049	-0.052 mg/dL Standard Deviation 0.1687	1.203 mg/dL Standard Deviation 0.5163	-0.012 mg/dL Standard Deviation 0.1057
Observed Value and Mean Change From Baseline in Serum Creatinine Day 15	1.306 mg/dL Standard Deviation 0.5229	0.032 mg/dL Standard Deviation 0.1634	1.218 mg/dL Standard Deviation 0.4838	-0.079 mg/dL Standard Deviation 0.1838	1.234 mg/dL Standard Deviation 0.5318	0.013 mg/dL Standard Deviation 0.1080
Observed Value and Mean Change From Baseline in Serum Creatinine Day 29	1.316 mg/dL Standard Deviation 0.6564	0.043 mg/dL Standard Deviation 0.3106	1.290 mg/dL Standard Deviation 0.5247	-0.030 mg/dL Standard Deviation 0.1956	1.229 mg/dL Standard Deviation 0.5427	0.014 mg/dL Standard Deviation 0.1060
Observed Value and Mean Change From Baseline in Serum Creatinine Day 57	1.292 mg/dL Standard Deviation 0.6252	0.034 mg/dL Standard Deviation 0.1377	1.265 mg/dL Standard Deviation 0.5514	-0.056 mg/dL Standard Deviation 0.1096	1.200 mg/dL Standard Deviation 0.4977	0.017 mg/dL Standard Deviation 0.1516
Observed Value and Mean Change From Baseline in Serum Creatinine Day 85	1.285 mg/dL Standard Deviation 0.5621	0.025 mg/dL Standard Deviation 0.1725	1.226 mg/dL Standard Deviation 0.4711	-0.050 mg/dL Standard Deviation 0.2002	1.251 mg/dL Standard Deviation 0.5409	0.030 mg/dL Standard Deviation 0.1371
Observed Value and Mean Change From Baseline in Serum Creatinine Day 113	1.243 mg/dL Standard Deviation 0.5404	-0.017 mg/dL Standard Deviation 0.1859	1.226 mg/dL Standard Deviation 0.5367	-0.051 mg/dL Standard Deviation 0.0985	1.243 mg/dL Standard Deviation 0.5169	0.019 mg/dL Standard Deviation 0.1361
Observed Value and Mean Change From Baseline in Serum Creatinine Day 169, End of Study	1.295 mg/dL Standard Deviation 0.6468	0.043 mg/dL Standard Deviation 0.2242	1.284 mg/dL Standard Deviation 0.5878	-0.032 mg/dL Standard Deviation 0.1839	1.280 mg/dL Standard Deviation 0.5169	0.026 mg/dL Standard Deviation 0.1370

SECONDARY outcome

Timeframe: Baseline up to 24 weeks

Population: Intent-to-Treat Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=29 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Day 169, End of Study	66.05 mL/min/1.73 m^2 Standard Deviation 28.012	-0.56 mL/min/1.73 m^2 Standard Deviation 11.079	67.89 mL/min/1.73 m^2 Standard Deviation 28.783	2.19 mL/min/1.73 m^2 Standard Deviation 6.456	67.70 mL/min/1.73 m^2 Standard Deviation 28.158	-1.67 mL/min/1.73 m^2 Standard Deviation 6.474
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Day 113	66.80 mL/min/1.73 m^2 Standard Deviation 26.168	0.72 mL/min/1.73 m^2 Standard Deviation 10.277	69.77 mL/min/1.73 m^2 Standard Deviation 27.114	2.34 mL/min/1.73 m^2 Standard Deviation 6.130	69.91 mL/min/1.73 m^2 Standard Deviation 28.493	-0.32 mL/min/1.73 m^2 Standard Deviation 6.673
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Baseline	65.38 mL/min/1.73 m^2 Standard Deviation 25.691	—	64.94 mL/min/1.73 m^2 Standard Deviation 27.960	—	71.95 mL/min/1.73 m^2 Standard Deviation 28.186	—
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Day 8	63.62 mL/min/1.73 m^2 Standard Deviation 26.433	-1.77 mL/min/1.73 m^2 Standard Deviation 9.218	66.31 mL/min/1.73 m^2 Standard Deviation 27.442	1.37 mL/min/1.73 m^2 Standard Deviation 7.400	72.57 mL/min/1.73 m^2 Standard Deviation 28.443	1.13 mL/min/1.73 m^2 Standard Deviation 5.947
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Day 15	63.02 mL/min/1.73 m^2 Standard Deviation 25.313	-2.36 mL/min/1.73 m^2 Standard Deviation 8.119	69.15 mL/min/1.73 m^2 Standard Deviation 28.175	3.09 mL/min/1.73 m^2 Standard Deviation 9.005	70.47 mL/min/1.73 m^2 Standard Deviation 28.419	-0.68 mL/min/1.73 m^2 Standard Deviation 7.230
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Day 29	65.74 mL/min/1.73 m^2 Standard Deviation 27.747	0.35 mL/min/1.73 m^2 Standard Deviation 10.433	66.12 mL/min/1.73 m^2 Standard Deviation 28.001	1.18 mL/min/1.73 m^2 Standard Deviation 7.296	71.19 mL/min/1.73 m^2 Standard Deviation 28.935	-0.26 mL/min/1.73 m^2 Standard Deviation 5.992
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Day 57	66.57 mL/min/1.73 m^2 Standard Deviation 27.555	-0.26 mL/min/1.73 m^2 Standard Deviation 7.962	67.55 mL/min/1.73 m^2 Standard Deviation 28.026	2.61 mL/min/1.73 m^2 Standard Deviation 5.496	71.98 mL/min/1.73 m^2 Standard Deviation 28.075	-0.56 mL/min/1.73 m^2 Standard Deviation 7.175
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Day 85	64.33 mL/min/1.73 m^2 Standard Deviation 24.940	-1.75 mL/min/1.73 m^2 Standard Deviation 9.425	68.44 mL/min/1.73 m^2 Standard Deviation 25.535	1.00 mL/min/1.73 m^2 Standard Deviation 7.818	69.87 mL/min/1.73 m^2 Standard Deviation 29.764	-0.87 mL/min/1.73 m^2 Standard Deviation 6.522

SECONDARY outcome

Timeframe: Baseline up to 24 weeks

Population: Intent-to-Treat Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=29 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Day 15	134.4 mmHg Standard Deviation 16.25	1.0 mmHg Standard Deviation 11.53	136.5 mmHg Standard Deviation 9.10	4.4 mmHg Standard Deviation 8.41	135.3 mmHg Standard Deviation 12.60	1.0 mmHg Standard Deviation 12.82
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Day 29	135.7 mmHg Standard Deviation 11.16	2.2 mmHg Standard Deviation 9.02	137.7 mmHg Standard Deviation 10.99	6.3 mmHg Standard Deviation 11.55	133.8 mmHg Standard Deviation 12.04	-0.2 mmHg Standard Deviation 12.58
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Baseline	133.4 mmHg Standard Deviation 10.61	—	131.4 mmHg Standard Deviation 8.63	—	133.9 mmHg Standard Deviation 11.32	—
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Day 8	135.1 mmHg Standard Deviation 14.21	1.7 mmHg Standard Deviation 12.58	133.9 mmHg Standard Deviation 9.17	2.6 mmHg Standard Deviation 7.37	135.7 mmHg Standard Deviation 11.31	1.6 mmHg Standard Deviation 12.03
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Day 57	135.1 mmHg Standard Deviation 12.75	1.0 mmHg Standard Deviation 12.00	134.7 mmHg Standard Deviation 13.93	3.3 mmHg Standard Deviation 12.44	133.1 mmHg Standard Deviation 13.98	-0.8 mmHg Standard Deviation 12.60
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Day 85	131.5 mmHg Standard Deviation 13.88	-2.6 mmHg Standard Deviation 12.93	134.9 mmHg Standard Deviation 10.69	2.3 mmHg Standard Deviation 10.93	135.7 mmHg Standard Deviation 14.99	1.9 mmHg Standard Deviation 13.15
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Day 113	136.2 mmHg Standard Deviation 15.13	2.3 mmHg Standard Deviation 12.23	136.9 mmHg Standard Deviation 8.45	4.3 mmHg Standard Deviation 10.17	133.5 mmHg Standard Deviation 12.93	0.4 mmHg Standard Deviation 12.09
Observed Value and Mean Change From Baseline in Systolic Blood Pressure Day 169, End of Study	141.0 mmHg Standard Deviation 12.00	6.4 mmHg Standard Deviation 10.55	132.7 mmHg Standard Deviation 13.24	1.0 mmHg Standard Deviation 12.20	134.6 mmHg Standard Deviation 15.17	1.1 mmHg Standard Deviation 16.51

SECONDARY outcome

Timeframe: Baseline up to 24 weeks

Population: Intent-to-Treat Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=29 Participants Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change n=56 Participants Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Baseline	75.5 mmHg Standard Deviation 8.55	—	73.4 mmHg Standard Deviation 11.22	—	75.5 mmHg Standard Deviation 8.88	—
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Day 8	76.1 mmHg Standard Deviation 8.22	0.6 mmHg Standard Deviation 8.95	75.4 mmHg Standard Deviation 11.00	2.0 mmHg Standard Deviation 5.75	75.3 mmHg Standard Deviation 9.73	-0.3 mmHg Standard Deviation 7.94
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Day 15	74.7 mmHg Standard Deviation 7.34	-0.9 mmHg Standard Deviation 7.36	77.2 mmHg Standard Deviation 10.75	3.5 mmHg Standard Deviation 6.52	74.4 mmHg Standard Deviation 8.99	-1.0 mmHg Standard Deviation 6.84
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Day 29	77.2 mmHg Standard Deviation 6.49	1.7 mmHg Standard Deviation 5.84	78.0 mmHg Standard Deviation 8.58	4.5 mmHg Standard Deviation 8.36	75.0 mmHg Standard Deviation 9.01	-0.6 mmHg Standard Deviation 8.17
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Day 57	76.1 mmHg Standard Deviation 7.07	0.2 mmHg Standard Deviation 6.90	76.8 mmHg Standard Deviation 9.74	3.3 mmHg Standard Deviation 9.36	72.6 mmHg Standard Deviation 9.96	-2.5 mmHg Standard Deviation 7.58
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Day 85	74.2 mmHg Standard Deviation 6.57	-1.7 mmHg Standard Deviation 7.56	77.3 mmHg Standard Deviation 11.00	3.1 mmHg Standard Deviation 7.67	73.3 mmHg Standard Deviation 10.19	-1.5 mmHg Standard Deviation 7.88
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Day 113	75.7 mmHg Standard Deviation 7.20	-0.2 mmHg Standard Deviation 6.40	77.8 mmHg Standard Deviation 9.94	3.6 mmHg Standard Deviation 7.01	73.3 mmHg Standard Deviation 9.75	-1.4 mmHg Standard Deviation 7.33
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure Day 169, End of Study	77.0 mmHg Standard Deviation 8.06	0.8 mmHg Standard Deviation 7.83	76.0 mmHg Standard Deviation 11.00	2.1 mmHg Standard Deviation 8.78	73.7 mmHg Standard Deviation 10.88	-1.0 mmHg Standard Deviation 8.19

SECONDARY outcome

Timeframe: Up to 120 minutes after the IV loading dose for CSL346

Population: Pharmacokinetic (PK) Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples	234.26 ug/mL Standard Deviation 671.392	182.32 ug/mL Standard Deviation 140.886	—	—	—	—

SECONDARY outcome

Timeframe: Up to 120 minutes after the IV loading dose for CSL346

Population: PK Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Time to Reach Cmax in Serum (Tmax) After IV Loading Dose of CSL346 in Serum Samples	0.52 Hours Interval 0.0 to 2.0	0.55 Hours Interval 0.0 to 2.0	—	—	—	—

SECONDARY outcome

Timeframe: From Day 1 to Day 29

Population: PK Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Cmax After First Subcutaneous (SC) Dose of CSL346 in Serum Samples	34.70 ug/mL Standard Deviation 11.405	67.88 ug/mL Standard Deviation 29.565	—	—	—	—

SECONDARY outcome

Timeframe: From Day 1 to Day 29

Population: PK Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Tmax After First SC Dose of CSL346 in Serum Samples	168.05 Hours Interval 119.1 to 671.0	167.58 Hours Interval 118.1 to 336.2	—	—	—	—

SECONDARY outcome

Timeframe: From Day 1 to Day 29

Population: PK Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Area Under the Concentration-time Curve in First Dosing Interval	19374.474 Hours*ug/mL Standard Deviation 5560.5651	37225.571 Hours*ug/mL Standard Deviation 13026.7980	—	—	—	—

SECONDARY outcome

Timeframe: 29 days after each dose

Population: PK Analysis Set

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Trough Concentration After Each Dose After first SC dose	15.306 ug/mL Standard Deviation 5.9479	28.215 ug/mL Standard Deviation 9.6135	—	—	—	—
Trough Concentration After Each Dose After second SC dose	16.686 ug/mL Standard Deviation 7.0049	31.541 ug/mL Standard Deviation 9.3408	—	—	—	—
Trough Concentration After Each Dose After third SC dose	15.959 ug/mL Standard Deviation 8.1791	31.522 ug/mL Standard Deviation 10.1988	—	—	—	—
Trough Concentration After Each Dose After fourth SC dose	16.225 ug/mL Standard Deviation 6.2157	30.544 ug/mL Standard Deviation 10.6822	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 4, 8, and 16

Population: Safety Analysis Set

Data are presented for participants who received treatment with CSL346. Any anti-drug antibodies detected in participants who received treatment with Placebo were considered not specific to CSL346 and of no clinical relevance.

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Number of Subjects Positive for Anti-drug Antibodies Week 4	4 Participants	0 Participants	—	—	—	—
Number of Subjects Positive for Anti-drug Antibodies Week 8	4 Participants	0 Participants	—	—	—	—
Number of Subjects Positive for Anti-drug Antibodies Week 16	5 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 4, 8, and 16

Population: Safety Analysis Set

Data are presented for participants who received treatment with CSL346. Any anti-drug antibodies detected in participants who received treatment with Placebo were considered not specific to CSL346 and of no clinical relevance.

Outcome measures

Outcome measures
Measure	CSL346 (Low Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 Participants Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline	CSL346 (High Dose) - Change Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions. CSL346: VEGF-B antagonist monoclonal antibody. Change from Baseline.	Placebo - Observed Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Observed value.	Placebo - Change Administered as a single IV loading dose followed by SC infusions. Placebo: Normal saline. Change from Baseline.
Percentage of Subjects Positive for Anti-drug Antibodies Week 16	17.9 Percentage of participants	0 Percentage of participants	—	—	—	—
Percentage of Subjects Positive for Anti-drug Antibodies Week 4	13.8 Percentage of participants	0 Percentage of participants	—	—	—	—
Percentage of Subjects Positive for Anti-drug Antibodies Week 8	14.3 Percentage of participants	0 Percentage of participants	—	—	—	—

Adverse Events

CSL346 (Low Dose)

Serious events: 3 serious events

Other events: 17 other events

Deaths: 1 deaths

CSL346 (High Dose)

Serious events: 6 serious events

Other events: 11 other events

Deaths: 1 deaths

Placebo

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

CSL Behring

Phone: 610-878-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	CSL346 (Low Dose) n=29 participants at risk Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 participants at risk Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=54 participants at risk Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline
Infections and infestations Campylobacter gastroenteritis	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Infections and infestations Subdural abscess	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Infections and infestations Urinary tract infection	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Infections and infestations Urosepsis	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Injury, poisoning and procedural complications Fall	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Injury, poisoning and procedural complications Head injury	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Injury, poisoning and procedural complications Traumatic fracture	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Cardiac disorders Acute myocardial infarction	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Cardiac disorders Paroxysmal atrioventricular block	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Ear and labyrinth disorders Ear pain	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Gastrointestinal disorders Vomiting	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
General disorders Non-cardiac chest pain	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Investigations Brain natriuretic peptide increased	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Investigations Glomerular filtration rate decreased	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Musculoskeletal and connective tissue disorders Arthralgia	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Nervous system disorders Amnesia	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Renal and urinary disorders Albuminuria	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.

Measure	CSL346 (Low Dose) n=29 participants at risk Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	CSL346 (High Dose) n=29 participants at risk Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions CSL346: VEGF-B antagonist monoclonal antibody	Placebo n=54 participants at risk Administered as a single IV loading dose followed by SC infusions Placebo: Normal saline
Infections and infestations COVID-19	17.2% 5/29 • Number of events 5 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	10.3% 3/29 • Number of events 3 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.7% 2/54 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Infections and infestations Upper respiratory tract infection	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Infections and infestations Tooth infection	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Investigations Blood creatinine increased	10.3% 3/29 • Number of events 4 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	5.6% 3/54 • Number of events 4 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Investigations C-reactive protein increased	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
General disorders Oedema peripheral	10.3% 3/29 • Number of events 3 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
General disorders Injection site pain	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
General disorders Injection site swelling	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	5.6% 3/54 • Number of events 5 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Musculoskeletal and connective tissue disorders Arthralgia	10.3% 3/29 • Number of events 3 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	6.9% 2/29 • Number of events 3 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Musculoskeletal and connective tissue disorders Back pain	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.4% 1/29 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	7.4% 4/54 • Number of events 4 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Renal and urinary disorders Albuminuria	10.3% 3/29 • Number of events 5 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	6.9% 2/29 • Number of events 3 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	3.7% 2/54 • Number of events 3 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Renal and urinary disorders Acute kidney injury	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Metabolism and nutrition disorders Hyperkalaemia	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	1.9% 1/54 • Number of events 1 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Gastrointestinal disorders Constipation	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.
Nervous system disorders Dizziness	6.9% 2/29 • Number of events 2 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/29 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.	0.00% 0/54 • Adverse Event data are presented for the Treatment Period (12 weeks) and the Follow-up Period (up to 12 weeks after the participant's last dose of Investigational Product in the Treatment Period). Adverse Event data are presented for the Safety Analysis Set.