Diabetic Kidney Disease (DKD)
Conditions
Brief summary
This phase 2a, double-blind, randomized, placebo-controlled study will assess the efficacy, safety, tolerability, and pharmacokinetics (PK), of repeat doses of CSL346 in subjects with diabetic kidney disease (DKD) and albuminuria receiving standard of care treatment.
Interventions
BIOLOGICALCSL346
VEGF-B antagonist monoclonal antibody
DRUGPlacebo
Normal saline
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects ≥ 25 years of age with a diagnosis of type 2 diabetes mellitus (T2DM) * Urinary ACR ≥ 150 mg/g * eGFR \> 20 mL/min/1.73m2 * Glycosylated HbA1c \< 12%
Exclusion criteria
* Current diagnosis of type 1 diabetes mellitus * History of acute kidney injury or chronic dialysis/renal transplant * Uncontrolled hypertension or class III / IV heart failure * Left ventricular ejection fraction \< 50% by echocardiogram * Troponin-I \> the upper reference limit * b-type natriuretic peptide \> 200 pg/mL * ALT \> 2x the upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR) | Baseline up to Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With TEAEs | Up to 24 weeks | — |
| Number of Subjects With Adverse Events of Special Interest (AESIs) | Up to 24 weeks | Data are presented for treatment-emergent AESIs. |
| Percentage of Subjects With AESIs | Up to 24 weeks | Data are presented for treatment-emergent AESIs. |
| Observed Value and Mean Change From Baseline in Serum Creatinine | Baseline up to 24 weeks | — |
| Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Baseline up to 24 weeks | — |
| Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Baseline up to 24 weeks | — |
| Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Baseline up to 24 weeks | — |
| Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | Up to 24 weeks | — |
| Time to Reach Cmax in Serum (Tmax) After IV Loading Dose of CSL346 in Serum Samples | Up to 120 minutes after the IV loading dose for CSL346 | — |
| Cmax After First Subcutaneous (SC) Dose of CSL346 in Serum Samples | From Day 1 to Day 29 | — |
| Tmax After First SC Dose of CSL346 in Serum Samples | From Day 1 to Day 29 | — |
| Area Under the Concentration-time Curve in First Dosing Interval | From Day 1 to Day 29 | — |
| Trough Concentration After Each Dose | 29 days after each dose | — |
| Number of Subjects Positive for Anti-drug Antibodies | Weeks 4, 8, and 16 | 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. |
| Percentage of Subjects Positive for Anti-drug Antibodies | Weeks 4, 8, and 16 | 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. |
| Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples | Up to 120 minutes after the IV loading dose for CSL346 | — |
Countries
Australia, Canada, Israel, New Zealand, Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at study centers in Australia, Canada, Israel, New Zealand, Puerto Rico and the United States.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| CSL346 (Low Dose) Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
CSL346: VEGF-B antagonist monoclonal antibody | 29 |
| CSL346 (High Dose) Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
CSL346: VEGF-B antagonist monoclonal antibody | 29 |
| Placebo Administered as a single IV loading dose followed by SC infusions
Placebo: Normal saline | 56 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Not treated with IP | 0 | 0 | 2 |
| Overall Study | Pandemic related | 0 | 0 | 1 |
| Overall Study | Reason not known | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Total | Placebo | CSL346 (High Dose) | CSL346 (Low Dose) |
|---|---|---|---|---|
| Age, Continuous | 62.0 Years | 63.0 Years | 61.0 Years | 62.0 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 19 Participants | 9 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 37 Participants | 20 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 5 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 8 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 12 Participants | 8 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 72 Participants | 35 Participants | 19 Participants | 18 Participants |
| Region of Enrollment Australia | 13 participants | 6 participants | 4 participants | 3 participants |
| Region of Enrollment Canada | 4 participants | 3 participants | 1 participants | 0 participants |
| Region of Enrollment Israel | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment New Zealand | 23 participants | 10 participants | 5 participants | 8 participants |
| Region of Enrollment Puerto Rico | 9 participants | 5 participants | 1 participants | 3 participants |
| Region of Enrollment United States | 64 participants | 32 participants | 18 participants | 14 participants |
| Sex: Female, Male Female | 28 Participants | 11 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 86 Participants | 45 Participants | 22 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 29 | 1 / 29 | 0 / 54 |
| other Total, other adverse events | 17 / 29 | 11 / 29 | 18 / 54 |
| serious Total, serious adverse events | 3 / 29 | 6 / 29 | 5 / 54 |
Outcome results
Primary
Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR)
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.
Time frame: Baseline up to Week 16
Population: Intent to Treat Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CSL346 (Low Dose) | Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR) | 3.2 Geometric Mean of Percent Change |
| CSL346 (High Dose) | Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR) | 17.7 Geometric Mean of Percent Change |
| Placebo | Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR) | 5.4 Geometric Mean of Percent Change |
p-value: 0.48580% CI: [-14.8, 16.3]Mixed Models Repeated Measures Analysis
p-value: 0.7580% CI: [-7.2, 27.2]Mixed Models Repeated Measures Analysis
Secondary
Area Under the Concentration-time Curve in First Dosing Interval
Time frame: From Day 1 to Day 29
Population: PK Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSL346 (Low Dose) | Area Under the Concentration-time Curve in First Dosing Interval | 19374.474 Hours*ug/mL | Standard Deviation 5560.5651 |
| CSL346 (High Dose) | Area Under the Concentration-time Curve in First Dosing Interval | 37225.571 Hours*ug/mL | Standard Deviation 13026.798 |
Secondary
Cmax After First Subcutaneous (SC) Dose of CSL346 in Serum Samples
Time frame: From Day 1 to Day 29
Population: PK Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSL346 (Low Dose) | Cmax After First Subcutaneous (SC) Dose of CSL346 in Serum Samples | 34.70 ug/mL | Standard Deviation 11.405 |
| CSL346 (High Dose) | Cmax After First Subcutaneous (SC) Dose of CSL346 in Serum Samples | 67.88 ug/mL | Standard Deviation 29.565 |
Secondary
Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples
Time frame: Up to 120 minutes after the IV loading dose for CSL346
Population: Pharmacokinetic (PK) Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSL346 (Low Dose) | Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples | 234.26 ug/mL | Standard Deviation 671.392 |
| CSL346 (High Dose) | Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples | 182.32 ug/mL | Standard Deviation 140.886 |
Secondary
Number of Subjects Positive for Anti-drug Antibodies
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.
Time frame: Weeks 4, 8, and 16
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CSL346 (Low Dose) | Number of Subjects Positive for Anti-drug Antibodies | Week 4 | 4 Participants |
| CSL346 (Low Dose) | Number of Subjects Positive for Anti-drug Antibodies | Week 8 | 4 Participants |
| CSL346 (Low Dose) | Number of Subjects Positive for Anti-drug Antibodies | Week 16 | 5 Participants |
| CSL346 (High Dose) | Number of Subjects Positive for Anti-drug Antibodies | Week 4 | 0 Participants |
| CSL346 (High Dose) | Number of Subjects Positive for Anti-drug Antibodies | Week 8 | 0 Participants |
| CSL346 (High Dose) | Number of Subjects Positive for Anti-drug Antibodies | Week 16 | 0 Participants |
Secondary
Number of Subjects With Adverse Events of Special Interest (AESIs)
Data are presented for treatment-emergent AESIs.
Time frame: Up to 24 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSL346 (Low Dose) | Number of Subjects With Adverse Events of Special Interest (AESIs) | 10 Participants |
| CSL346 (High Dose) | Number of Subjects With Adverse Events of Special Interest (AESIs) | 6 Participants |
| Placebo | Number of Subjects With Adverse Events of Special Interest (AESIs) | 13 Participants |
Secondary
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 24 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSL346 (Low Dose) | Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 22 Participants |
| CSL346 (High Dose) | Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 23 Participants |
| Placebo | Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 32 Participants |
Secondary
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure
Time frame: Baseline up to 24 weeks
Population: Intent-to-Treat Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 15 | 74.7 mmHg | Standard Deviation 7.34 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Baseline | 75.5 mmHg | Standard Deviation 8.55 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 169, End of Study | 77.0 mmHg | Standard Deviation 8.06 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 113 | 75.7 mmHg | Standard Deviation 7.2 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 8 | 76.1 mmHg | Standard Deviation 8.22 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 85 | 74.2 mmHg | Standard Deviation 6.57 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 57 | 76.1 mmHg | Standard Deviation 7.07 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 29 | 77.2 mmHg | Standard Deviation 6.49 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 8 | 0.6 mmHg | Standard Deviation 8.95 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 15 | -0.9 mmHg | Standard Deviation 7.36 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 29 | 1.7 mmHg | Standard Deviation 5.84 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 57 | 0.2 mmHg | Standard Deviation 6.9 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 85 | -1.7 mmHg | Standard Deviation 7.56 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 113 | -0.2 mmHg | Standard Deviation 6.4 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 169, End of Study | 0.8 mmHg | Standard Deviation 7.83 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 169, End of Study | 76.0 mmHg | Standard Deviation 11 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 113 | 77.8 mmHg | Standard Deviation 9.94 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 8 | 75.4 mmHg | Standard Deviation 11 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Baseline | 73.4 mmHg | Standard Deviation 11.22 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 57 | 76.8 mmHg | Standard Deviation 9.74 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 29 | 78.0 mmHg | Standard Deviation 8.58 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 15 | 77.2 mmHg | Standard Deviation 10.75 |
| Placebo | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 85 | 77.3 mmHg | Standard Deviation 11 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 85 | 3.1 mmHg | Standard Deviation 7.67 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 29 | 4.5 mmHg | Standard Deviation 8.36 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 57 | 3.3 mmHg | Standard Deviation 9.36 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 8 | 2.0 mmHg | Standard Deviation 5.75 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 169, End of Study | 2.1 mmHg | Standard Deviation 8.78 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 15 | 3.5 mmHg | Standard Deviation 6.52 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 113 | 3.6 mmHg | Standard Deviation 7.01 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 15 | 74.4 mmHg | Standard Deviation 8.99 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 29 | 75.0 mmHg | Standard Deviation 9.01 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 169, End of Study | 73.7 mmHg | Standard Deviation 10.88 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 57 | 72.6 mmHg | Standard Deviation 9.96 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 85 | 73.3 mmHg | Standard Deviation 10.19 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Baseline | 75.5 mmHg | Standard Deviation 8.88 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 113 | 73.3 mmHg | Standard Deviation 9.75 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 8 | 75.3 mmHg | Standard Deviation 9.73 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 29 | -0.6 mmHg | Standard Deviation 8.17 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 8 | -0.3 mmHg | Standard Deviation 7.94 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 15 | -1.0 mmHg | Standard Deviation 6.84 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 113 | -1.4 mmHg | Standard Deviation 7.33 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 57 | -2.5 mmHg | Standard Deviation 7.58 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 85 | -1.5 mmHg | Standard Deviation 7.88 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Diastolic Blood Pressure | Day 169, End of Study | -1.0 mmHg | Standard Deviation 8.19 |
Secondary
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline up to 24 weeks
Population: Intent-to-Treat Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL346 (Low Dose) | 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 |
| CSL346 (Low Dose) | 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 |
| CSL346 (Low Dose) | 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 |
| CSL346 (Low Dose) | 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 |
| CSL346 (Low Dose) | 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 |
| CSL346 (Low Dose) | 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 |
| CSL346 (Low Dose) | 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 24.94 |
| CSL346 (Low Dose) | 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 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 113 | 0.72 mL/min/1.73 m^2 | Standard Deviation 10.277 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 8 | -1.77 mL/min/1.73 m^2 | Standard Deviation 9.218 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 15 | -2.36 mL/min/1.73 m^2 | Standard Deviation 8.119 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 29 | 0.35 mL/min/1.73 m^2 | Standard Deviation 10.433 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 57 | -0.26 mL/min/1.73 m^2 | Standard Deviation 7.962 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 85 | -1.75 mL/min/1.73 m^2 | Standard Deviation 9.425 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 169, End of Study | -0.56 mL/min/1.73 m^2 | Standard Deviation 11.079 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 57 | 67.55 mL/min/1.73 m^2 | Standard Deviation 28.026 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 113 | 69.77 mL/min/1.73 m^2 | Standard Deviation 27.114 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 15 | 69.15 mL/min/1.73 m^2 | Standard Deviation 28.175 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 29 | 66.12 mL/min/1.73 m^2 | Standard Deviation 28.001 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Baseline | 64.94 mL/min/1.73 m^2 | Standard Deviation 27.96 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 8 | 66.31 mL/min/1.73 m^2 | Standard Deviation 27.442 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 85 | 68.44 mL/min/1.73 m^2 | Standard Deviation 25.535 |
| Placebo | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 169, End of Study | 67.89 mL/min/1.73 m^2 | Standard Deviation 28.783 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 169, End of Study | 2.19 mL/min/1.73 m^2 | Standard Deviation 6.456 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 29 | 1.18 mL/min/1.73 m^2 | Standard Deviation 7.296 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 8 | 1.37 mL/min/1.73 m^2 | Standard Deviation 7.4 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 113 | 2.34 mL/min/1.73 m^2 | Standard Deviation 6.13 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 85 | 1.00 mL/min/1.73 m^2 | Standard Deviation 7.818 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 57 | 2.61 mL/min/1.73 m^2 | Standard Deviation 5.496 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 15 | 3.09 mL/min/1.73 m^2 | Standard Deviation 9.005 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 113 | 69.91 mL/min/1.73 m^2 | Standard Deviation 28.493 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 15 | 70.47 mL/min/1.73 m^2 | Standard Deviation 28.419 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 8 | 72.57 mL/min/1.73 m^2 | Standard Deviation 28.443 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 57 | 71.98 mL/min/1.73 m^2 | Standard Deviation 28.075 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 169, End of Study | 67.70 mL/min/1.73 m^2 | Standard Deviation 28.158 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 85 | 69.87 mL/min/1.73 m^2 | Standard Deviation 29.764 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Baseline | 71.95 mL/min/1.73 m^2 | Standard Deviation 28.186 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 29 | 71.19 mL/min/1.73 m^2 | Standard Deviation 28.935 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 15 | -0.68 mL/min/1.73 m^2 | Standard Deviation 7.23 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 29 | -0.26 mL/min/1.73 m^2 | Standard Deviation 5.992 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 57 | -0.56 mL/min/1.73 m^2 | Standard Deviation 7.175 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 85 | -0.87 mL/min/1.73 m^2 | Standard Deviation 6.522 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 113 | -0.32 mL/min/1.73 m^2 | Standard Deviation 6.673 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 169, End of Study | -1.67 mL/min/1.73 m^2 | Standard Deviation 6.474 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Day 8 | 1.13 mL/min/1.73 m^2 | Standard Deviation 5.947 |
Secondary
Observed Value and Mean Change From Baseline in Serum Creatinine
Time frame: Baseline up to 24 weeks
Population: Intent-to-Treat Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 29 | 1.316 mg/dL | Standard Deviation 0.6564 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 15 | 1.306 mg/dL | Standard Deviation 0.5229 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Baseline | 1.273 mg/dL | Standard Deviation 0.5502 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 8 | 1.306 mg/dL | Standard Deviation 0.5374 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 169, End of Study | 1.295 mg/dL | Standard Deviation 0.6468 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 113 | 1.243 mg/dL | Standard Deviation 0.5404 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 85 | 1.285 mg/dL | Standard Deviation 0.5621 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 57 | 1.292 mg/dL | Standard Deviation 0.6252 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 113 | -0.017 mg/dL | Standard Deviation 0.1859 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 8 | 0.032 mg/dL | Standard Deviation 0.19 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 15 | 0.032 mg/dL | Standard Deviation 0.1634 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 29 | 0.043 mg/dL | Standard Deviation 0.3106 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 57 | 0.034 mg/dL | Standard Deviation 0.1377 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 85 | 0.025 mg/dL | Standard Deviation 0.1725 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 169, End of Study | 0.043 mg/dL | Standard Deviation 0.2242 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 57 | 1.265 mg/dL | Standard Deviation 0.5514 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 169, End of Study | 1.284 mg/dL | Standard Deviation 0.5878 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 15 | 1.218 mg/dL | Standard Deviation 0.4838 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 29 | 1.290 mg/dL | Standard Deviation 0.5247 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 113 | 1.226 mg/dL | Standard Deviation 0.5367 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Baseline | 1.321 mg/dL | Standard Deviation 0.5592 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 85 | 1.226 mg/dL | Standard Deviation 0.4711 |
| Placebo | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 8 | 1.269 mg/dL | Standard Deviation 0.5049 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 169, End of Study | -0.032 mg/dL | Standard Deviation 0.1839 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 29 | -0.030 mg/dL | Standard Deviation 0.1956 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 113 | -0.051 mg/dL | Standard Deviation 0.0985 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 85 | -0.050 mg/dL | Standard Deviation 0.2002 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 57 | -0.056 mg/dL | Standard Deviation 0.1096 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 8 | -0.052 mg/dL | Standard Deviation 0.1687 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 15 | -0.079 mg/dL | Standard Deviation 0.1838 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 113 | 1.243 mg/dL | Standard Deviation 0.5169 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 15 | 1.234 mg/dL | Standard Deviation 0.5318 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 8 | 1.203 mg/dL | Standard Deviation 0.5163 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 57 | 1.200 mg/dL | Standard Deviation 0.4977 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 169, End of Study | 1.280 mg/dL | Standard Deviation 0.5169 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 85 | 1.251 mg/dL | Standard Deviation 0.5409 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Baseline | 1.207 mg/dL | Standard Deviation 0.5184 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 29 | 1.229 mg/dL | Standard Deviation 0.5427 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 15 | 0.013 mg/dL | Standard Deviation 0.108 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 29 | 0.014 mg/dL | Standard Deviation 0.106 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 57 | 0.017 mg/dL | Standard Deviation 0.1516 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 85 | 0.030 mg/dL | Standard Deviation 0.1371 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 113 | 0.019 mg/dL | Standard Deviation 0.1361 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 169, End of Study | 0.026 mg/dL | Standard Deviation 0.137 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Serum Creatinine | Day 8 | -0.012 mg/dL | Standard Deviation 0.1057 |
Secondary
Observed Value and Mean Change From Baseline in Systolic Blood Pressure
Time frame: Baseline up to 24 weeks
Population: Intent-to-Treat Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 8 | 135.1 mmHg | Standard Deviation 14.21 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 15 | 134.4 mmHg | Standard Deviation 16.25 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 169, End of Study | 141.0 mmHg | Standard Deviation 12 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Baseline | 133.4 mmHg | Standard Deviation 10.61 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 57 | 135.1 mmHg | Standard Deviation 12.75 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 85 | 131.5 mmHg | Standard Deviation 13.88 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 113 | 136.2 mmHg | Standard Deviation 15.13 |
| CSL346 (Low Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 29 | 135.7 mmHg | Standard Deviation 11.16 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 15 | 1.0 mmHg | Standard Deviation 11.53 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 113 | 2.3 mmHg | Standard Deviation 12.23 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 169, End of Study | 6.4 mmHg | Standard Deviation 10.55 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 85 | -2.6 mmHg | Standard Deviation 12.93 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 8 | 1.7 mmHg | Standard Deviation 12.58 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 57 | 1.0 mmHg | Standard Deviation 12 |
| CSL346 (High Dose) | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 29 | 2.2 mmHg | Standard Deviation 9.02 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 8 | 133.9 mmHg | Standard Deviation 9.17 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 85 | 134.9 mmHg | Standard Deviation 10.69 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 113 | 136.9 mmHg | Standard Deviation 8.45 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 15 | 136.5 mmHg | Standard Deviation 9.1 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 29 | 137.7 mmHg | Standard Deviation 10.99 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Baseline | 131.4 mmHg | Standard Deviation 8.63 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 57 | 134.7 mmHg | Standard Deviation 13.93 |
| Placebo | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 169, End of Study | 132.7 mmHg | Standard Deviation 13.24 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 15 | 4.4 mmHg | Standard Deviation 8.41 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 29 | 6.3 mmHg | Standard Deviation 11.55 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 85 | 2.3 mmHg | Standard Deviation 10.93 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 113 | 4.3 mmHg | Standard Deviation 10.17 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 57 | 3.3 mmHg | Standard Deviation 12.44 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 169, End of Study | 1.0 mmHg | Standard Deviation 12.2 |
| CSL346 (High Dose) - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 8 | 2.6 mmHg | Standard Deviation 7.37 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 15 | 135.3 mmHg | Standard Deviation 12.6 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 29 | 133.8 mmHg | Standard Deviation 12.04 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 57 | 133.1 mmHg | Standard Deviation 13.98 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 85 | 135.7 mmHg | Standard Deviation 14.99 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 113 | 133.5 mmHg | Standard Deviation 12.93 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 169, End of Study | 134.6 mmHg | Standard Deviation 15.17 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Baseline | 133.9 mmHg | Standard Deviation 11.32 |
| Placebo - Observed | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 8 | 135.7 mmHg | Standard Deviation 11.31 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 29 | -0.2 mmHg | Standard Deviation 12.58 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 8 | 1.6 mmHg | Standard Deviation 12.03 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 113 | 0.4 mmHg | Standard Deviation 12.09 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 85 | 1.9 mmHg | Standard Deviation 13.15 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 57 | -0.8 mmHg | Standard Deviation 12.6 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 15 | 1.0 mmHg | Standard Deviation 12.82 |
| Placebo - Change | Observed Value and Mean Change From Baseline in Systolic Blood Pressure | Day 169, End of Study | 1.1 mmHg | Standard Deviation 16.51 |
Secondary
Percentage of Subjects Positive for Anti-drug Antibodies
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.
Time frame: Weeks 4, 8, and 16
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL346 (Low Dose) | Percentage of Subjects Positive for Anti-drug Antibodies | Week 16 | 17.9 Percentage of participants |
| CSL346 (Low Dose) | Percentage of Subjects Positive for Anti-drug Antibodies | Week 4 | 13.8 Percentage of participants |
| CSL346 (Low Dose) | Percentage of Subjects Positive for Anti-drug Antibodies | Week 8 | 14.3 Percentage of participants |
| CSL346 (High Dose) | Percentage of Subjects Positive for Anti-drug Antibodies | Week 4 | 0 Percentage of participants |
| CSL346 (High Dose) | Percentage of Subjects Positive for Anti-drug Antibodies | Week 8 | 0 Percentage of participants |
| CSL346 (High Dose) | Percentage of Subjects Positive for Anti-drug Antibodies | Week 16 | 0 Percentage of participants |
Secondary
Percentage of Subjects With AESIs
Data are presented for treatment-emergent AESIs.
Time frame: Up to 24 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL346 (Low Dose) | Percentage of Subjects With AESIs | 34.5 Percentage of participants |
| CSL346 (High Dose) | Percentage of Subjects With AESIs | 20.7 Percentage of participants |
| Placebo | Percentage of Subjects With AESIs | 24.1 Percentage of participants |
Secondary
Percentage of Subjects With TEAEs
Time frame: Up to 24 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL346 (Low Dose) | Percentage of Subjects With TEAEs | 75.9 Percentage of participants |
| CSL346 (High Dose) | Percentage of Subjects With TEAEs | 79.3 Percentage of participants |
| Placebo | Percentage of Subjects With TEAEs | 59.3 Percentage of participants |
Secondary
Time to Reach Cmax in Serum (Tmax) After IV Loading Dose of CSL346 in Serum Samples
Time frame: Up to 120 minutes after the IV loading dose for CSL346
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CSL346 (Low Dose) | Time to Reach Cmax in Serum (Tmax) After IV Loading Dose of CSL346 in Serum Samples | 0.52 Hours |
| CSL346 (High Dose) | Time to Reach Cmax in Serum (Tmax) After IV Loading Dose of CSL346 in Serum Samples | 0.55 Hours |
Secondary
Tmax After First SC Dose of CSL346 in Serum Samples
Time frame: From Day 1 to Day 29
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CSL346 (Low Dose) | Tmax After First SC Dose of CSL346 in Serum Samples | 168.05 Hours |
| CSL346 (High Dose) | Tmax After First SC Dose of CSL346 in Serum Samples | 167.58 Hours |
Secondary
Trough Concentration After Each Dose
Time frame: 29 days after each dose
Population: PK Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL346 (Low Dose) | Trough Concentration After Each Dose | After first SC dose | 15.306 ug/mL | Standard Deviation 5.9479 |
| CSL346 (Low Dose) | Trough Concentration After Each Dose | After second SC dose | 16.686 ug/mL | Standard Deviation 7.0049 |
| CSL346 (Low Dose) | Trough Concentration After Each Dose | After third SC dose | 15.959 ug/mL | Standard Deviation 8.1791 |
| CSL346 (Low Dose) | Trough Concentration After Each Dose | After fourth SC dose | 16.225 ug/mL | Standard Deviation 6.2157 |
| CSL346 (High Dose) | Trough Concentration After Each Dose | After fourth SC dose | 30.544 ug/mL | Standard Deviation 10.6822 |
| CSL346 (High Dose) | Trough Concentration After Each Dose | After first SC dose | 28.215 ug/mL | Standard Deviation 9.6135 |
| CSL346 (High Dose) | Trough Concentration After Each Dose | After third SC dose | 31.522 ug/mL | Standard Deviation 10.1988 |
| CSL346 (High Dose) | Trough Concentration After Each Dose | After second SC dose | 31.541 ug/mL | Standard Deviation 9.3408 |