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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Kidney Disease (DKD)
• Intervention / Treatment: Drug: Placebo; Biological: CSL346

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Elizabeth Vale, Australia, 5112
    • Lyell McEwin Hospital
  • New South Wales
    • Merewether, New South Wales, Australia, 2291
      • Hunter Diabetes Centre - The AIM Centre
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's hospital
    • Heidelberg, Victoria, Australia, 3084
      • The Austin Hospital
    • Parkville, Victoria, Australia, 3052
      • The Royal Melbourne Hospital
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • 1240130 - University Health Network
• Israel
  • Reẖovot, Israel, 76100
    • 3760045 - Kaplan Medical Center
  • Tel Aviv-Yafo, Israel, 64239
    • 3760044 - Tel Aviv Sourasky Medical Center
• New Zealand
  • Auckland, New Zealand, 2025
    • Middlemore Hospital
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Christchurch, New Zealand, 8011
    • Lipid and Diabetes Research Group
  • Wellington, New Zealand, 6140
    • Endocrine Associates - Wellington
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundación de Investigación
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico - Puerto Rico Clinical and TRC
• United States
  • California
    • Covina, California, United States, 91702
      • California Kidney Specialists (CKS) - Citrus Office
    • Fresno, California, United States, 93720
      • Valley Research - Fresno
    • Lomita, California, United States, 90717
      • Torrance Clinical Research (TCR) - Lomita
    • Lynwood, California, United States, 90260
      • Renal Medical Associate/NARI
    • Northridge, California, United States, 91324
      • Amicis Research Center
    • Northridge, California, United States, 91324
      • California Medical Research Associates, Inc
    • Riverside, California, United States, 92503
      • Riverside Nephrology Group
  • Florida
    • Ocoee, Florida, United States, 34761
      • West Orange Endocrinology
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Omega Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Springfield, Massachusetts, United States, 01107
      • Renal and Transplant Associates
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health System
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Medical Group, LLC - Las Vegas
  • New York
    • Staten Island, New York, United States, 10301
      • Center for Thyroid & Parathyroid Disorders
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physicians East, P.A. - Endocrinology
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University School of Medicine
  • Texas
    • Houston, Texas, United States, 77040
      • Juno Research, L.L.C.
    • Houston, Texas, United States, 77079
      • The Endocrine Center
    • San Antonio, Texas, United States, 78215
      • Renal Associates, P.A. - San Antonio
    • San Antonio, Texas, United States, 78224
      • Primary Care Providers of Texas
    • San Antonio, Texas, United States, 78231
      • Diabetes and Metabolism Specialists (DMS) - San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSL346 (low dose); Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions	Biological: CSL346; VEGF-B antagonist monoclonal antibody
Experimental: CSL346 (high dose); Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions	Biological: CSL346; VEGF-B antagonist monoclonal antibody
Placebo Comparator: Placebo; Administered as a single IV loading dose followed by SC infusions	Drug: Placebo; Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)		Up to 24 weeks
Percentage of Subjects With TEAEs		Up to 24 weeks
Number of Subjects With Adverse Events of Special Interest (AESIs)	Data are presented for treatment-emergent AESIs.	Up to 24 weeks
Percentage of Subjects With AESIs	Data are presented for treatment-emergent 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 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
Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples		Up to 120 minutes after the IV loading dose for CSL346
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	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
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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): October 24, 2022

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 3, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: CSL346_2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No