A Phase 2a, Double-blind, Randomized, Placebo-controlled, Proof of Concept Study of Vascular Endothelial Growth Factor (VEGF)-B Blockade With the Monoclonal Antibody CSL346 in Subjects With Diabetic Kidney Disease

CSL Behring37 sites in 6 countries114 target enrollmentSeptember 14, 2020

ConditionsDiabetic Kidney Disease (DKD)

InterventionsCSL346 Placebo

Overview

Phase: Phase 2
Intervention: CSL346
Conditions: Diabetic Kidney Disease (DKD)
Sponsor: CSL Behring
Enrollment: 114
Locations: 37
Primary Endpoint: Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 14, 2020

End Date

October 24, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

CSL Behring

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

CSL346 (low dose)

Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions

Intervention: CSL346

CSL346 (high dose)

Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions

Intervention: CSL346

Placebo

Administered as a single IV loading dose followed by SC infusions

Intervention: Placebo

Outcomes

Primary Outcomes

Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR)

Time Frame: 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 Outcomes

Number of Subjects With Adverse Events of Special Interest (AESIs)(Up to 24 weeks)
Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline up to 24 weeks)
Percentage of Subjects With TEAEs(Up to 24 weeks)
Observed Value and Mean Change From Baseline in Systolic Blood Pressure(Baseline up to 24 weeks)
Percentage of Subjects With AESIs(Up to 24 weeks)
Observed Value and Mean Change From Baseline in Serum Creatinine(Baseline up to 24 weeks)
Observed Value and Mean Change From Baseline in Diastolic Blood Pressure(Baseline 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)
Maximum Concentration (Cmax) After Intravenous (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)
Area Under the Concentration-time Curve in First Dosing Interval(From Day 1 to Day 29)
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)(Up to 24 weeks)
Tmax After First SC Dose of CSL346 in Serum Samples(From Day 1 to Day 29)
Number of Subjects Positive for Anti-drug Antibodies(Weeks 4, 8, and 16)
Trough Concentration After Each Dose(29 days after each dose)
Percentage of Subjects Positive for Anti-drug Antibodies(Weeks 4, 8, and 16)