Home » Trials » SLCTR/2025/017
Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of WAL0921 in Patients with Glomerular Kidney Diseases and Proteinuria
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SLCTR Registration Number
SLCTR/2025/017
Date of Registration
The date of last modification
Apr 25, 2025
Scientific Title of Trial
Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of WAL0921 in Patients with Glomerular Kidney Diseases and Proteinuria
Public Title of Trial
Safety and Efficacy of WAL0921 vs Placebo in Patients with Glomerular Kidney Diseases and Proteinuria – A Phase 2 Randomized Controlled Trial
Disease or Health Condition(s) Studied
Glomerular Kidney Diseases and Proteinuria
Scientific Acronym
None
Public Acronym
WALDEN
Brief title
Safety and Efficacy of WAL0921 in Patients with Glomerular Kidney Diseases with Proteinuria
Universal Trial Number
U1111-1319-7829
Any other number(s) assigned to the trial and issuing authority
ClinicalTrials.gov (NCT06466135), WAL0921-02, ERC, Faculty of Medicine, University of Kelaniya reference number: P/139/09/2024
What is the research question being addressed?
Is WAL0921 effective and safe in the treatment of glomerular kidney diseases with proteinuria ?
Type of study
Interventional
Study design
Allocation
Randomized controlled trial
Masking
Double blinded : Participants, Investigators, Healthcare providers
Control
Placebo
Assignment
Parallel
Purpose
Treatment
Study Phase
Phase 2
Intervention(s) planned
Study sites: The National Hospital of Sri Lanka, General Sir John Kotelawala Defense University, Teaching Hospital Kurunegala, Jaffna Teaching Hospital, National Hospital Kandy.
Randomization: Subject’s screening data will be entered in the Almac IXRS system by the site personnel which include subject data, screening date and informed consent date. Post screening, in the system, subjects may be listed as screen failed, rescreened or randomized to treatment based on a computer-generated randomization schedule prepared before the study by or under the supervision of the statistician or delegate.
Subjects have meeting all of the eligibility criteria will be assigned to either active treatment (IV doses (2 mg/kg or 6mg/kg) of the humanized monoclonal antibody WAL0921) or placebo groups (sodium chloride 0.9% (normal saline) USP, sterile grade).
Intervention arm Participants will be administered 7 sequential, IV doses of WAL0921 every 14 days (Days 0, 14, 28, 42, 56, 70, and 84) over a 12-week treatment period.
Control arm Commercially obtained placebo (0.9% normal saline, USP, sterile grade) procured by the local clinical site staff will be administered every 14 days (Days 0, 14, 28, 42, 56, 70, and 84) over a 12-week treatment period.
All subjects will be followed for 24 weeks after their last dose of study drug with follow-up visits on Days 126, 168, 210, and 252.
WAL0921 or placebo dose preparation in Study WAL0921-02 is undertaken by an authorized and unblinded pharmacist in identical IV bags as per the WAL0921 Dose Preparation Record (DPR) and information on subject randomization to the treatment group as per the Almac IXRS system. The prepared IV bags are subsequently labeled to maintain the study blind prior to provisioning the same to the dose administration and HCP staff.
Inclusion criteria
1.Adults, aged 18-65 years 2. Biological males and females 3. Diagnosis of one of the following glomerular kidney diseases: diabetic nephropathy; primary focal segmental glomerulosclerosis; treatment resistant-minimal change disease; primary IgA nephropathy; primary membranous nephropathy 4. eGFR greater than or equal to 30 mL/min/1.73 m2
Exclusion criteria
Primary outcome(s)
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1.
Incidence of treatment-emergent adverse events (TEAEs). As per the completed Phase 1 Study WAL0921-01 in healthy volunteers, following adverse-events (treatment related or unrelated) are anticipated in Study WAL0921-02 are: o Headache o Dizziness o Paresthesia o Somnolence o Nausea o Diarrhoea o Vomiting |
[ At 4, 8, 12, 18, 24, 30, and 36 weeks ] |
|
2.
Efficacy assessment in the Phase 2 Study AL0921-02 involves measurement of a change in baseline proteinuria from 24-hr urine collection at the specified timepoints. Proteinuria is defined as:Ratio of urine albumin or urine protein to urine creatinine and is expressed as mg/g units |
[ At 4, 8, 12, 18, 24, 30, and 36 weeks ] |
Secondary outcome(s)
|
1.
Clinically significant changes in safety laboratory parameters, physical examination (PE) findings, vital signs, or ECGs (including QTcF - QT interval corrected by Fridericia's formula). Safety lab listing: • Urine chemistry: 24 h total volume urine (ml), Creatinine 24h urine (mg/24hr), Microalb/cre ratio, 24h (mg/g), Microalbumin, 24hr ur (mg/24hr), Protein, 24hr urine (mg/24hr), Protein/cre ratio, 24hr (mg/g), Creatinine, random urine (mg/dl), Microalb/creat. Ratio (mg/g), Microalbumin, Random (mg/l)Protein, random ur (mg/dl), Protein/cre ratio (ran) (mg/g) • Chemistry: Alanine Aminotransferase (U/L),Albumin (g/dL), Alkaline Phosphatase (U/L), Aspartate Aminotransferase (U/L), Bicarbonate (mmol/L), Calcium (mg/dL), Chloride (mmol/L), Creatinine (mg/dL), Direct Bilirubin (mg/dL), Glomerular Filtration Rate, Estimated (mL/min/1.73m^2), Glucose (mg/dL), Potassium (mmol/L), Protein (g/dL), Sodium (mmol/L), Total Bilirubin (mg/dL), Urea Nitrogen (mg/dL) • Coagulation: Activated Partial Thromboplastin Time (seconds), D-Dimer (ng/mL FEU), Prothrombin Intl. Normalized Ratio (value), Prothrombin Time (seconds) • Hematology: Basophils (10^3/uL), Basophils/ Leukocytes (%), Eosinophils (10^3/uL), Eosinophils/ Leukocytes (%), Ery. Mean Corpuscular HGB Concentration (g/dL), Ery. Mean Corpuscular Hemoglobin (pg), Ery. Mean Corpuscular Volume (fL), Erythrocytes (10^6/uL), Erythrocytes Distribution Width (%), Hematocrit (%), Hemoglobin (g/dL), Immature Granulocytes (10^3/uL), Immature Granulocytes/Leukocytes (%), Leukocytes (10^3/uL), Lymphocytes (10^3/uL), Lymphocytes/Leukocytes (%), Mean Platelet Volume (fL), Monocytes (10^3/uL), Monocytes/Leukocytes (%), Neutrophils (10^3/uL), Neutrophils/Leukocytes (%), Nucleated Erythrocytes (10^3/uL), Nucleated Erythrocytes/Leukocytes (%), Platelets (10^3/uL) • Serology: HIV-1/2 Antibody (reactive/non-reactive), Hepatitis B Core Antibody (positive/negative), Hepatitis B Virus Surface Antigen (positive/negative), Hepatitis C Virus Antibody (positive/negative) • Urinalysis: Creatinine (mg/dL), Glucose (positive/negative), Protein (mg/dL), Erythrocytes (/hpf), Leukocytes (/hpf), Bacteria (/hpf), Bilirubin (positive/negative), Calcium Oxalate Crystals (/hpf), Granular Casts (/lpf), Hyaline Casts (/lpf), Ketones (positive/negative), Leukocyte Esterase (positive/negative), Nitrite (positive/negative), Occult Blood (positive/negative), Protein/Creatinine (mg/g), RBC Casts (/lpf), Renal Tubular Epithelial Cells (/hpf), Specific Gravity (value), Squamous Epithelial Cells (/hpf), Transitional Epithelial Cells (/hpf), Triple Phosphate Crystals (/hpf), Uric Acid Crystals (/hpf), WBC Casts (/lpf), Waxy Casts (/lpf), Yeast Cells (/hpf), pH (value) • Urine Drug Screen: Amphetamine (ng/mL), Barbiturates (ng/mL), Benzodiazepine (ng/mL), Cannabinoids (ng/mL), Cocaine (ng/mL), Opiate (ng/mL) • Physical Examination: Assessment of head, eyes, ears, nose and throat (HEENT), respiratory, cardiovascular, and gastrointestinal systems, and any symptom-related body system as is consistent per site’s standard practice • Vital signs: Blood pressure (mm Hg; systolic: diastolic), Pulse (heart beats per minute), Respiration (breaths per minute), Temperature (°C or °F), Height (cm or m), Weight (lb. or kg), ECG (12-lead) |
[ 4, 8, 12, 18, 24, 30, and 36 weeks ] |
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2.
Percentage change from baseline, a. in urine albumin-creatinine ratio (UACR) or urine protein-creatinine ratio (UPCR) based on quantitative 24-hour urine collections at baseline; b. and spot urine UACR or UPCR assessed at baseline, |
[ 12, 18, 24, 30, and 36 weeks 4 and 8 weeks in subjects with diabetic nephropathy or rare glomerular disease ] |
|
3.
Percentage change from baseline in estimated glomerular filtration rate (eGFR) from baseline renal function |
[ 12, 18, 24, 30, and 36 weeks ] |
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4.
Slope of eGFR Calculation of egfr as per CKD-EPI 2021 equation Egfr Slope = (Change in egfr) / (Time elapsed in years), expressed as ml/min/1.73m²/year |
[ 12, 18, 24, 30, and 36 weeks ] |
|
5.
Proportion achieving a complete remission (CR), defined as UACR or UPCR < 0.5 g/g, in subjects with diabetic nephropathy (DN) or rare glomerular disease |
[ 12, 18, 24, 30, and 36 weeks ] |
|
6.
Proportion with a UACR or UPCR decrease of at least 30% from baseline in subjects with DN or rare glomerular disease |
[ 12, 18, 24, 30, and 36 weeks ] |
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7.
Proportion with a UACR or UPCR decrease of at least 40% from baseline in subjects with DN or rare glomerular disease |
[ 12, 18, 24, 30, and 36 weeks ] |
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8.
Proportion with a UACR or UPCR decrease of at least 50% from baseline in subjects with DN or rare glomerular disease |
[ 12, 18, 24, 30, and 36 weeks ] |
|
9.
Pharmacokinetic (PK) evaluation of plasma WAL0921 concentration: Maximum observed drug concentration (Cmax), Time of Cmax (Tmax), Area under the drug, Concentration-time curve (AUC), Elimination half-life (t1/2), Minimum observed drug concentration (Cmin/Ctrough) |
[ In DN subjects: Day -7, Day 0 pre-and post-dose, Day 1, 3, 5, 7, 14, 28, 42, 56, 70, 84 pre- and post-dose, 85, 87, 91, 98, 112, 126, 168, 210 and 252 In rare glomerular disease subjects: Day 0 pre- and post-dose, Day 14, 28, 42, 56, 70, 84 pre- and post-dose, 126, 168, 210 and 252 ] |
|
10.
Analysis of the relationship between positive anti-drug antibodies (ADA), if any, and WAL0921 exposure |
[ Pre-dose Day 0, 14, 28, 42, 56, 70, 84, 126, 168, 210 and 252 ] |
|
11.
Plasma total and free suPAR (soluble urokinase plasminogen activator receptor) concentrations |
[ In DN subjects: Day -7, Day 0 pre- and post-dose, Day 1, 3, 5, 7, 14, 28, 42, 56, 70, 84 pre- and post-dose, 85, 87, 91, 98, 112, 126, 168, 210 and 252 In rare glomerular disease subjects: Day 0 pre- and post-dose, Day 14, 28, 42, 56, 70, 84 pre- and post-dose, 126, 168, 210 and 252 ] |
|
12.
Urine total and free suPAR concentrations |
[ In DN subjects: Day -7, Day 0 pre- and post-dose, Day 1, 3, 5, 7, 14, 28, 42, 56, 70, 84 pre- and post-dose, 85, 87, 91, 98, 112, 126, 168, 210 and 252 In rare glomerular disease subjects: Day 0 pre- and post-dose, Day 14, 28, 42, 56, 70, 84 pre- and post-dose, 126, 168, 210 and 252 ] |
|
13.
Analyses of relationships between plasma and urine suPAR concentrations with WAL0921 exposure. |
[ 12, 18, 24, 30, and 36 weeks ] |
|
14.
Plasma free suPAR percent reduction from baseline |
[ 4, 8, 12, 18, 24, 30, and 36 weeks ] |
|
15.
Urine suPAR/creatinine ratios and percent reduction from baseline |
[ 12, 18, 24, 30, and 36 weeks ] |
Target number/sample size
Global: 96, Sri Lanka: 12 (9 active, 3 placebo)
Countries of recruitment
Australia, India, Korea, Democratic People's Republic of, Malaysia, Spain, Sri Lanka, United Kingdom, United States
Anticipated start date
2025-03-01
Anticipated end date
2027-04-20
Date of first enrollment
Date of study completion
Recruitment status
Pending
Funding source
Walden Biosciences, Inc., One Kendall Square, Building 700, Suite 7101 Cambridge, MA 02139 USA
Regulatory approvals
Pending
Status
Approved
Date of Approval
2024-09-10
Approval number
P/139/09/2024
Details of Ethics Review Committee
| Name: | Ethics Review Committee, Faculty of Medicine, University of Kelaniya |
| Institutional Address: | P.O Box 6, Thalagolla Road, Ragama, Sri Lanka |
| Telephone: | +94 11 2961267 |
| Email: | erckelaniya@gmail.com |
Contact person for Scientific Queries/Principal Investigator
Dr. Selvarajah Mathu, MBBS, MD
Consultant nephrologist
Ward 67, Nephrology and Transplant, National Hospital of Sri Lanka, Colombo 10-01000
N/A
0777390628
N/A
mathuselvarajah@gmail.com
N/A
Contact Person for Public Queries
Dr. Selvarajah Mathu, MBBS, MD
Consultant nephrologist
Ward 67, Nephrology and Transplant, National Hospital of Sri Lanka, Colombo 10-01000
N/A
0777390628
N/A
mathuselvarajah@gmail.com
N/A
Primary study sponsor/organization
Walden Biosciences, Inc
Walden Biosciences, Inc., One Kendall Square, Building 700, Suite 7102 Cambridge, MA 02139 USA
Tel: 8573141961
clinicaltrials@waldenbiosciences.com
Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?
No
IPD sharing plan description
N/A
Study protocol available
No
Protocol version and date
Not Available
Protocol URL
Not Available
Results summary available
No
Date of posting results
Date of study completion
Final sample size
Date of first publication
Link to results
Brief summary of results
