Vascular Endothelial Growth Factor-B (VEGF-B) Blockade With the Monoclonal Antibody CSL346 in Subjects With Diabetic Kidney Disease
Primary Purpose
Diabetic Kidney Disease (DKD)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CSL346
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Kidney Disease (DKD)
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 ≥ 60 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
Sites / Locations
- California Kidney Specialists (CKS) - Citrus Office
- Valley Research - Fresno
- Torrance Clinical Research (TCR) - Lomita
- Renal Medical Associate/NARI
- Amicis Research Center
- California Medical Research Associates, Inc
- Riverside Nephrology Group
- West Orange Endocrinology
- East-West Medical Research Institute
- Omega Clinical Research
- Tufts Medical Center
- Renal and Transplant Associates
- University of Missouri Health System
- Palm Medical Group, LLC - Las Vegas
- Center for Thyroid & Parathyroid Disorders
- Physicians East, P.A. - Endocrinology
- Vanderbilt University School of Medicine
- Juno Research, L.L.C.
- The Endocrine Center
- Renal Associates, P.A. - San Antonio
- Primary Care Providers of Texas
- Diabetes and Metabolism Specialists (DMS) - San Antonio
- Hunter Diabetes Centre - The AIM Centre
- St Vincent's Hospital
- The Austin Hospital
- The Royal Melbourne Hospital
- Sunshine Hospital
- Lyell McEwin Hospital
- 1240130 - University Health Network
- 3760045 - Kaplan Medical Center
- 3760044 - Tel Aviv Sourasky Medical Center
- Middlemore Hospital
- Christchurch Hospital
- Lipid and Diabetes Research Group
- Endocrine Associates - Wellington
- Fundación de Investigación
- University of Puerto Rico - Puerto Rico Clinical and TRC
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
CSL346 (low dose)
CSL346 (high dose)
Placebo
Arm Description
Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
Administered as a single IV loading dose followed by SC infusions
Outcomes
Primary Outcome Measures
Mean change in log-transformed urinary albumin-to-creatinine ratio (ACR)
Secondary Outcome Measures
Number of subjects with treatment-emergent adverse events (TEAEs)
Percentage of subjects with TEAEs
Number of subjects with adverse events of special interest (AESIs)
Percentage of subjects with AESIs
Observed value and mean change from Baseline in serum creatinine
Observed value and mean change from Baseline in estimated glomerular filtration rate (eGFR)
Observed value and mean change from Baseline in systolic blood pressure
Observed value and mean change from Baseline in diastolic blood pressure
Maximum concentration (Cmax) after IV loading dose of CSL346 in serum samples
Time to reach Cmax in serum (Tmax) after IV loading dose of CSL346 in serum samples
Cmax after first SC dose of CSL346 in serum samples
Tmax after first SC dose of CSL346 in serum samples
Area under the concentration-time curve in first dosing interval
Trough concentration after each dose
Number of subjects positive for anti-drug antibodies
Percentage of subjects positive for anti-drug antibodies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04419467
Brief Title
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
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 14, 2020 (Actual)
Primary Completion Date
October 24, 2022 (Actual)
Study Completion Date
October 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Kidney Disease (DKD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
114 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CSL346 (low dose)
Arm Type
Experimental
Arm Description
Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
Arm Title
CSL346 (high dose)
Arm Type
Experimental
Arm Description
Administered as a single intravenous (IV) loading dose followed by subcutaneous (SC) infusions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Administered as a single IV loading dose followed by SC infusions
Intervention Type
Biological
Intervention Name(s)
CSL346
Intervention Description
VEGF-B antagonist monoclonal antibody
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline
Primary Outcome Measure Information:
Title
Mean change in log-transformed urinary albumin-to-creatinine ratio (ACR)
Time Frame
Baseline up to Week 16
Secondary Outcome Measure Information:
Title
Number of subjects with treatment-emergent adverse events (TEAEs)
Time Frame
Up to 24 weeks
Title
Percentage of subjects with TEAEs
Time Frame
Up to 24 weeks
Title
Number of subjects with adverse events of special interest (AESIs)
Time Frame
Up to 24 weeks
Title
Percentage of subjects with AESIs
Time Frame
Up to 24 weeks
Title
Observed value and mean change from Baseline in serum creatinine
Time Frame
Baseline up to 24 weeks
Title
Observed value and mean change from Baseline in estimated glomerular filtration rate (eGFR)
Time Frame
Baseline up to 24 weeks
Title
Observed value and mean change from Baseline in systolic blood pressure
Time Frame
Baseline up to 24 weeks
Title
Observed value and mean change from Baseline in diastolic blood pressure
Time Frame
Baseline up to 24 weeks
Title
Maximum concentration (Cmax) after IV loading dose of CSL346 in serum samples
Time Frame
Up to 120 minutes after the IV loading dose for CSL346
Title
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
Title
Cmax after first SC dose of CSL346 in serum samples
Time Frame
From Day 1 to Day 29
Title
Tmax after first SC dose of CSL346 in serum samples
Time Frame
From Day 1 to Day 29
Title
Area under the concentration-time curve in first dosing interval
Time Frame
From Day 1 to Day 29
Title
Trough concentration after each dose
Time Frame
29 days after each dose
Title
Number of subjects positive for anti-drug antibodies
Time Frame
Weeks 4, 8, and 16
Title
Percentage of subjects positive for anti-drug antibodies
Time Frame
Weeks 4, 8, and 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
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 ≥ 60 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
California Kidney Specialists (CKS) - Citrus Office
City
Covina
State/Province
California
ZIP/Postal Code
91702
Country
United States
Facility Name
Valley Research - Fresno
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
Torrance Clinical Research (TCR) - Lomita
City
Lomita
State/Province
California
ZIP/Postal Code
90717
Country
United States
Facility Name
Renal Medical Associate/NARI
City
Lynwood
State/Province
California
ZIP/Postal Code
90260
Country
United States
Facility Name
Amicis Research Center
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
California Medical Research Associates, Inc
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
Riverside Nephrology Group
City
Riverside
State/Province
California
ZIP/Postal Code
92503
Country
United States
Facility Name
West Orange Endocrinology
City
Ocoee
State/Province
Florida
ZIP/Postal Code
34761
Country
United States
Facility Name
East-West Medical Research Institute
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96814
Country
United States
Facility Name
Omega Clinical Research
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Renal and Transplant Associates
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01107
Country
United States
Facility Name
University of Missouri Health System
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Palm Medical Group, LLC - Las Vegas
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
Facility Name
Center for Thyroid & Parathyroid Disorders
City
Staten Island
State/Province
New York
ZIP/Postal Code
10301
Country
United States
Facility Name
Physicians East, P.A. - Endocrinology
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Vanderbilt University School of Medicine
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Juno Research, L.L.C.
City
Houston
State/Province
Texas
ZIP/Postal Code
77040
Country
United States
Facility Name
The Endocrine Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77079
Country
United States
Facility Name
Renal Associates, P.A. - San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Primary Care Providers of Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78224
Country
United States
Facility Name
Diabetes and Metabolism Specialists (DMS) - San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78231
Country
United States
Facility Name
Hunter Diabetes Centre - The AIM Centre
City
Merewether
State/Province
New South Wales
ZIP/Postal Code
2291
Country
Australia
Facility Name
St Vincent's Hospital
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
The Austin Hospital
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
The Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Sunshine Hospital
City
St Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
Lyell McEwin Hospital
City
Elizabeth Vale
ZIP/Postal Code
5112
Country
Australia
Facility Name
1240130 - University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
3760045 - Kaplan Medical Center
City
Reẖovot
ZIP/Postal Code
76100
Country
Israel
Facility Name
3760044 - Tel Aviv Sourasky Medical Center
City
Tel Aviv-Yafo
ZIP/Postal Code
64239
Country
Israel
Facility Name
Middlemore Hospital
City
Auckland
ZIP/Postal Code
2025
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
Lipid and Diabetes Research Group
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
Endocrine Associates - Wellington
City
Wellington
ZIP/Postal Code
6140
Country
New Zealand
Facility Name
Fundación de Investigación
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Facility Name
University of Puerto Rico - Puerto Rico Clinical and TRC
City
San Juan
ZIP/Postal Code
00935
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Vascular Endothelial Growth Factor-B (VEGF-B) Blockade With the Monoclonal Antibody CSL346 in Subjects With Diabetic Kidney Disease
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