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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 24, 2022

Interventions

  • Biological: CSL346
    • VEGF-B antagonist monoclonal antibody
  • Drug: Placebo
    • Normal saline

Arms, Groups and Cohorts

  • Experimental: CSL346 (low dose)
    • Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
  • Experimental: CSL346 (high dose)
    • Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
  • Placebo Comparator: Placebo
    • Administered as a single IV loading dose followed by SC infusions

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 25 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • CSL Behring
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Study Director, Study Director, CSL Behring

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