A Phase 1b, Multicenter, Open-Label Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Mezagitamab (TAK-079) in Patients With Primary IgA Nephropathy in Combination With Stable Background Therapy
A Study of Mezagitamab in Adults With Primary Immunoglobulin A Nephropathy Receiving Stable Background Therapy
Nishizawa Atsushi
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Contact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Not Recruiting
Nov. 09, 2022
Nov. 09, 2022
16
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1. Renal biopsy report supporting diagnosis of primary IgAN or IgA vasculitis-associated nephritis within 10 years prior to the screening visit.
2. Urine protein to creatinine ratio (UPCR) greater than or equal to (>=) 1 milligram per milligram (mg/mg) or urine protein excretion (UPE) >=1 gram per day (g/day) by 24-hour urine collection during the screening period.
3. Estimated glomerular filtration rate (eGFR) >=45 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) at screening.
4. Receiving stable background therapy for IgAN (angiotensin-converting enzyme inhibitor [ACE-I] or angiotensin receptor blocker [ARB]) for 12 weeks prior to screening. The ACE-I and ARB dose should represent the maximum tolerated or maximum labeled dose, as determined by the investigator, for a minimum of 3 months and remain stable during the entire duration of the study.
1. Kidney biopsy confirming significant renal disease other than IgAN.
2. Secondary IgAN (such as with significant liver disease, inflammatory bowel disease, and seronegative spondyloarthropathies).
3. Evidence of rapidly progressive glomerulonephritis (loss of >=50 percent (%) of eGFR within 3 months prior to the screening visit).
4. Diagnosis of nephrotic syndrome defined as 24-hour proteinuria greater than (>) 3.5 g/day, hypoalbuminemia (smaller than [<] 30 g/dL) with or without peripheral edema at the screening visit.
5. Diagnosis of acute active extrarenal IgA vasculitis (Henoch-Schonlein purpura) manifested by the involvement of other organs (palpable purpura, abdominal pain, and arthritis) at the screening visit and within 1 year prior to the screening visit.
6. Previous treatment with immunosuppressive agents such as cyclophosphamide, mycophenolate mofetil (MMF), cyclosporine, azathioprine, calcineurin inhibitors within 6 months prior to the screening visit or expected use of any of these agents for the duration of the study.
7. Use of systemic corticosteroids within 4 months from screening visit or expected use for the duration of the study.
8. Use of B-cell-directed biologic therapies such as blisibimod, belimumab, rituximab, ocrelizumab or have used other biologics (example, anti-tumor necrosis factor [TNF], abatacept, anti-interleukin [IL]-6) within 6 months prior to the screening visit or expected use of any of these agents for the duration of the study.
9. Participation in another investigational study within 4 weeks or 5 half-lives of study drug, whichever is longer, before the screening visit (the 4-week window is derived from the date of the last study procedure, and/or AE related to the study procedure in the previous study, to the screening visit of the current study) or expected use of an investigational agent from another investigational study during the time of this study.
10. Administration of any vaccine within 28 days before the screening visit or of any live or live-attenuated vaccination planned for the duration of the study.
11. An opportunistic infection smaller than or equal to (<=) 12 weeks before screening visit or currently receiving treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as the lesion has resolved prior to Day 1.
12. A positive T-cell interferon-gamma release assay (TIGRA) (result through QuantiFERON-TB Gold test or T-Spot/Elispot) at the screening visit.
13. A positive test result for hepatitis B surface antigen, or hepatitis B core antibody, or hepatitis C antibody, or HIV antibody/antigen at screening. However, an individual who has a known history of chronic hepatitis C and has been treated and fully cured of the disease, confirmed with a negative hepatitis C virus RNA polymerase chain reaction (PCR) test at screening, is not excluded on the basis of the positive hepatitis C antibody alone.
14. Inadequate organ and bone marrow function at screening visit.
15. Presence of uncontrolled or New York Heart Association (NYHA 1994) Class 3 or 4 congestive heart failure at the screening visit.
16. Uncontrolled diabetes manifested by glycosylated hemoglobin (HbA1c) >8% at the screening visit.
17. Current malignancy or history of malignancy during the previous 5 years, except adequately treated basal cell or squamous cell carcinomas of the skin or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix.
18age old over
No limit
Both
Kidney Disease, Glomerulonephritis
TAK-079 (Mezagitamab)
Mezagitamab, subcutaneous injection, once weekly for 8 weeks then once every 2 weeks for 16 weeks in the Main Study. Same dosing regimen will be repeated in LTE Retreatment Period.
1. Main Study: Percentage of Participants With one or More Treatment-emergent Adverse Events (TEAEs), Grade 3 or Higher TEAEs, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Mezagitamab Discontinuation
Time Frame: Up to Week 48
The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
2. LTE Observation Period: Percentage of Participants With one or More TEAEs, Grade 3 or Higher TEAEs and SAEs
Time Frame: Up to Week 96
The severity of TEAEs will be graded using NCI-CTCAE version 5.0.
3. LTE Retreatment Period: Percentage of Participants With one or More TEAEs, SAEs, Grade 3 or Higher TEAEs and AEs leading to Mezagitamab Discontinuation
Time Frame: Retreatment Week 0 to 48
The severity of TEAEs will be graded using NCI-CTCAE version 5.0.
1. Main Study: Ctrough: Observed Serum Trough Concentrations of Mezagitamab
Time Frame: Week 0 Pre-dose and at multiple time points (up to Week 48)
2. Main Study: Serum IgA Levels
Time Frame: Week 0 Pre-dose and at multiple time points (up to Week 48)
3. Main Study: Percent Change From Baseline in Proteinuria Based on Urine Protein to Creatinine Ratio (UPCR)
Time Frame: Week 36
UPCR is calculated by dividing the concentration of protein (milligram per deciliter [mg/dL]) in urine by the urine creatinine concentration (mg/dL).
4. Main Study: Percentage of Participants Based on Antidrug Antibody (ADA) Levels in Serum
Time Frame: Up to Week 48
Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.
5. LTE Observation Period: Serum IgA Levels
Time Frame: Week 56 Pre-dose and at multiple time points (up to Week 96)
6. LTE Observation Period: Percent Change From Baseline in Proteinuria Based on UPCR
Time Frame: Up to Week 96
UPCR is calculated by dividing the concentration of protein (mg/dL) in urine by the urine creatinine concentration (mg/dL).
7. LTE Observation Period: Percentage of Participants Based on ADA Levels in Serum
Time Frame: Up to Week 96
Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.
8. LTE Retreatment Period: Percentage of Participants Based on ADA Levels in Serum
Time Frame: Up to Retreatment Week 48
Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.
Takeda Pharmaceutical Company Limited
Sapporo City General Hospital Institutional Review Board
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
