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

Phase 2

Completed

• Conditions: Diabetic Kidney Disease (DKD)
• Interventions: Biological: CSL346; Drug: Placebo

• Registration Number: NCT04419467
• Lead Sponsor: CSL Behring

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-03
• Study First Submitted QC: 2020-06-03
• Study First Posted: 2020-06-05
• Study Start: 2020-09-14
• Primary Completion: 2022-10-24
• Study Completion: 2022-10-24
• Results First Submitted: 2023-10-24
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-05
• Last Update Submitted: 2023-12-05
• Results First Posted: 2023-12-06
• Last Update Posted: 2023-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 114

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSL346 (high dose)	CSL346	Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
Placebo	Placebo	Administered as a single IV loading dose followed by SC infusions
CSL346 (low dose)	CSL346	Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of Subjects With Adverse Events of Special Interest (AESIs)	Up to 24 weeks	Data are presented for treatment-emergent AESIs.
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
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 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
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.
Trough Concentration After Each Dose	29 days after each dose
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.
Percentage of Subjects With TEAEs	Up to 24 weeks
Tmax After First SC Dose of CSL346 in Serum Samples	From Day 1 to Day 29

Trial Locations

Locations (37)

California Kidney Specialists (CKS) - Citrus Office; 🇺🇸 Covina, California, United States

Valley Research - Fresno; 🇺🇸 Fresno, California, United States

Torrance Clinical Research (TCR) - Lomita; 🇺🇸 Lomita, California, United States

Renal Medical Associate/NARI; 🇺🇸 Lynwood, California, United States

Amicis Research Center; 🇺🇸 Northridge, California, United States

California Medical Research Associates, Inc; 🇺🇸 Northridge, California, United States

Riverside Nephrology Group; 🇺🇸 Riverside, California, United States

West Orange Endocrinology; 🇺🇸 Ocoee, Florida, United States

East-West Medical Research Institute; 🇺🇸 Honolulu, Hawaii, United States

Omega Clinical Research; 🇺🇸 Metairie, Louisiana, United States

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