Clinical trial NCT04419467: Vascular Endothelial Growth Factor-B (VEGF-B) Blockade With the Monoclonal Antibody CSL346 in Subjects With Diabetic Kidney Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Kidney Disease (DKD)
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-06-05
Enrollment: 114
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percent Change From Baseline in Urinary Albumin-to-creatinine Ratio (ACR)
timeFrame: Baseline up to Week 16
Secondary outcomes:
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 24 weeks
measure: Percentage of Subjects With TEAEs
timeFrame: Up to 24 weeks
measure: Number of Subjects With Adverse Events of Special Interest (AESIs)
timeFrame: Up to 24 weeks
measure: Percentage of Subjects With AESIs
timeFrame: Up to 24 weeks
measure: Observed Value and Mean Change From Baseline in Serum Creatinine
timeFrame: Baseline up to 24 weeks
measure: Observed Value and Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline up to 24 weeks
measure: Observed Value and Mean Change From Baseline in Systolic Blood Pressure
timeFrame: Baseline up to 24 weeks
measure: Observed Value and Mean Change From Baseline in Diastolic Blood Pressure
timeFrame: Baseline up to 24 weeks
measure: Maximum Concentration (Cmax) After Intravenous (IV) Loading Dose of CSL346 in Serum Samples
timeFrame: Up to 120 minutes after the IV loading dose for CSL346
measure: Time to Reach Cmax in Serum (Tmax) After IV Loading Dose of CSL346 in Serum Samples
timeFrame: Up to 120 minutes after the IV loading dose for CSL346
measure: Cmax After First Subcutaneous (SC) Dose of CSL346 in Serum Samples
timeFrame: From Day 1 to Day 29
measure: Tmax After First SC Dose of CSL346 in Serum Samples
timeFrame: From Day 1 to Day 29
measure: Area Under the Concentration-time Curve in First Dosing Interval
timeFrame: From Day 1 to Day 29
measure: Trough Concentration After Each Dose
timeFrame: 29 days after each dose
measure: Number of Subjects Positive for Anti-drug Antibodies
timeFrame: Weeks 4, 8, and 16
measure: Percentage of Subjects Positive for Anti-drug Antibodies
timeFrame: Weeks 4, 8, and 16
Other outcomes:
Locations:
city: Covina
country: United States
facility: California Kidney Specialists (CKS) - Citrus Office
state: California
city: Fresno
country: United States
facility: Valley Research - Fresno
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research (TCR) - Lomita
state: California
city: Lynwood
country: United States
facility: Renal Medical Associate/NARI
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Northridge
country: United States
facility: California Medical Research Associates, Inc
state: California
city: Riverside
country: United States
facility: Riverside Nephrology Group
state: California
city: Ocoee
country: United States
facility: West Orange Endocrinology
state: Florida
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Metairie
country: United States
facility: Omega Clinical Research
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Renal and Transplant Associates
state: Massachusetts
city: Columbia
country: United States
facility: University of Missouri Health System
state: Missouri
city: Las Vegas
country: United States
facility: Palm Medical Group, LLC - Las Vegas
state: Nevada
city: Staten Island
country: United States
facility: Center for Thyroid & Parathyroid Disorders
state: New York
city: Greenville
country: United States
facility: Physicians East, P.A. - Endocrinology
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Houston
country: United States
facility: Juno Research, L.L.C.
state: Texas
city: Houston
country: United States
facility: The Endocrine Center
state: Texas
city: San Antonio
country: United States
facility: Renal Associates, P.A. - San Antonio
state: Texas
city: San Antonio
country: United States
facility: Primary Care Providers of Texas
state: Texas
city: San Antonio
country: United States
facility: Diabetes and Metabolism Specialists (DMS) - San Antonio
state: Texas
city: Merewether
country: Australia
facility: Hunter Diabetes Centre - The AIM Centre
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: The Austin Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
city: Toronto
country: Canada
facility: 1240130 - University Health Network
state: Ontario
city: Reẖovot
country: Israel
facility: 3760045 - Kaplan Medical Center
city: Tel Aviv-Yafo
country: Israel
facility: 3760044 - Tel Aviv Sourasky Medical Center
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Christchurch
country: New Zealand
facility: Lipid and Diabetes Research Group
city: Wellington
country: New Zealand
facility: Endocrine Associates - Wellington
city: San Juan
country: Puerto Rico
facility: Fundación de Investigación
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico - Puerto Rico Clinical and TRC
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: