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

Diabetic Kidney Disease (DKD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04419467
• Other study ID #: CSL346_2001
• Status: Completed
• Phase: Phase 2
• Start date: September 14, 2020
• Est. completion date: October 24, 2022

Study information

• Verified date: December 2023
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: October 24, 2022
• Est. primary completion date: October 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Kidney Disease (DKD)
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Biological:
• CSL346
VEGF-B antagonist monoclonal antibody

Drug:
• Placebo
Normal saline

Locations

Country	Name	City	State
Australia	Lyell McEwin Hospital	Elizabeth Vale
Australia	St Vincent's Hospital	Fitzroy	Victoria
Australia	The Austin Hospital	Heidelberg	Victoria
Australia	Hunter Diabetes Centre - The AIM Centre	Merewether	New South Wales
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Sunshine Hospital	St Albans	Victoria
Canada	1240130 - University Health Network	Toronto	Ontario
Israel	3760045 - Kaplan Medical Center	Re?ovot
Israel	3760044 - Tel Aviv Sourasky Medical Center	Tel Aviv-Yafo
New Zealand	Middlemore Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Lipid and Diabetes Research Group	Christchurch
New Zealand	Endocrine Associates - Wellington	Wellington
Puerto Rico	Fundación de Investigación	San Juan
Puerto Rico	University of Puerto Rico - Puerto Rico Clinical and TRC	San Juan
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Missouri Health System	Columbia	Missouri
United States	California Kidney Specialists (CKS) - Citrus Office	Covina	California
United States	Valley Research - Fresno	Fresno	California
United States	Physicians East, P.A. - Endocrinology	Greenville	North Carolina
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Juno Research, L.L.C.	Houston	Texas
United States	The Endocrine Center	Houston	Texas
United States	Palm Medical Group, LLC - Las Vegas	Las Vegas	Nevada
United States	Torrance Clinical Research (TCR) - Lomita	Lomita	California
United States	Renal Medical Associate/NARI	Lynwood	California
United States	Omega Clinical Research	Metairie	Louisiana
United States	Vanderbilt University School of Medicine	Nashville	Tennessee
United States	Amicis Research Center	Northridge	California
United States	California Medical Research Associates, Inc	Northridge	California
United States	West Orange Endocrinology	Ocoee	Florida
United States	Riverside Nephrology Group	Riverside	California
United States	Diabetes and Metabolism Specialists (DMS) - San Antonio	San Antonio	Texas
United States	Primary Care Providers of Texas	San Antonio	Texas
United States	Renal Associates, P.A. - San Antonio	San Antonio	Texas
United States	Renal and Transplant Associates	Springfield	Massachusetts
United States	Center for Thyroid & Parathyroid Disorders	Staten Island	New York

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel,  New Zealand,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline up to Week 16
Secondary	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)		Up to 24 weeks
Secondary	Percentage of Subjects With TEAEs		Up to 24 weeks
Secondary	Number of Subjects With Adverse Events of Special Interest (AESIs)	Data are presented for treatment-emergent AESIs.	Up to 24 weeks
Secondary	Percentage of Subjects With AESIs	Data are presented for treatment-emergent AESIs.	Up to 24 weeks
Secondary	Observed Value and Mean Change From Baseline in Serum Creatinine		Baseline up to 24 weeks
Secondary	Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)		Baseline up to 24 weeks
Secondary	Observed Value and Mean Change From Baseline in Systolic Blood Pressure		Baseline up to 24 weeks
Secondary	Observed Value and Mean Change From Baseline in Diastolic Blood Pressure		Baseline up to 24 weeks
Secondary	Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples		Up to 120 minutes after the IV loading dose for CSL346
Secondary	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
Secondary	Cmax After First Subcutaneous (SC) Dose of CSL346 in Serum Samples		From Day 1 to Day 29
Secondary	Tmax After First SC Dose of CSL346 in Serum Samples		From Day 1 to Day 29
Secondary	Area Under the Concentration-time Curve in First Dosing Interval		From Day 1 to Day 29
Secondary	Trough Concentration After Each Dose		29 days after each dose
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.	Weeks 4, 8, and 16
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.	Weeks 4, 8, and 16