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A Study of Mezagitamab in Adults With Primary Immunoglobulin A Nephropathy Receiving Stable Background Therapy

Primary Purpose

Kidney Disease, Glomerulonephritis

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Mezagitamab
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Disease focused on measuring Drug Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Renal biopsy report supporting diagnosis of primary IgAN or IgA vasculitis-associated nephritis within 10 years prior to the screening visit.
  2. 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.

Exclusion Criteria:

  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-Schönlein 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.

    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.

  8. 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.
  9. 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.
  10. 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.
  11. A positive T-cell interferon-gamma release assay (TIGRA) (result through QuantiFERON-TB Gold test or T-Spot/Elispot) at the screening visit.
  12. 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.
  13. Inadequate organ and bone marrow function at screening visit.
  14. Presence of uncontrolled or New York Heart Association (NYHA 1994) Class 3 or 4 congestive heart failure at the screening visit.
  15. Uncontrolled diabetes manifested by glycosylated hemoglobin (HbA1c) >8% at the screening visit.
  16. 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.

Sites / Locations

  • Amicis Research Center - Northridge - Nordhoff
  • Boise Kidney and Hypertension Institute - Frenova
  • NorthShore University HealthSystem
  • Core Research Group
  • Monash Health, Monash Medical Centre
  • Royal Melbourne Hospital
  • Beijing Friendship Hospital,Capital Medical University
  • Guangdong Provincial Peoples Hospital
  • The First Affiliated Hospital of Xi'an Jiaotong University
  • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
  • Semmelweis Egyetem
  • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
  • Kasugai Municipal Hospital
  • Fujita Health University Hospital
  • Hiroshima University Hospital
  • Sapporo City General Hospital
  • Seoul National University Hospital
  • Ajou University Hospital
  • National University Hospital- Singapore
  • Hospital Universitario Marques de Valdecilla
  • Hospital Universitario Vall d'Hebron - PPDS
  • Fundacio Puigvert
  • Taipei Medical University Shuang Ho Hospital
  • National Taiwan University Hospital
  • Leicester General Hospital
  • Hull Royal Infirmary

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mezagitamab

Arm Description

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.

Outcomes

Primary Outcome Measures

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
The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
LTE Observation Period: Percentage of Participants With one or More TEAEs, Grade 3 or Higher TEAEs and SAEs
The severity of TEAEs will be graded using NCI-CTCAE version 5.0.
LTE Retreatment Period: Percentage of Participants With one or More TEAEs, SAEs, Grade 3 or Higher TEAEs and AEs leading to Mezagitamab Discontinuation
The severity of TEAEs will be graded using NCI-CTCAE version 5.0.

Secondary Outcome Measures

Main Study: Ctrough: Observed Serum Trough Concentrations of Mezagitamab
Main Study: Serum IgA Levels
Main Study: Percent Change From Baseline in Proteinuria Based on Urine Protein to Creatinine Ratio (UPCR)
UPCR is calculated by dividing the concentration of protein (milligram per deciliter [mg/dL]) in urine by the urine creatinine concentration (mg/dL).
Main Study: Percentage of Participants Based on Antidrug Antibody (ADA) Levels in Serum
Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.
LTE Observation Period: Serum IgA Levels
LTE Observation Period: Percent Change From Baseline in Proteinuria Based on UPCR
UPCR is calculated by dividing the concentration of protein (mg/dL) in urine by the urine creatinine concentration (mg/dL).
LTE Observation Period: Percentage of Participants Based on ADA Levels in Serum
LTE Retreatment Period: Percentage of Participants Based on ADA Levels in Serum
Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.

Full Information

First Posted
December 14, 2021
Last Updated
August 10, 2023
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT05174221
Brief Title
A Study of Mezagitamab in Adults With Primary Immunoglobulin A Nephropathy Receiving Stable Background Therapy
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 9, 2022 (Actual)
Primary Completion Date
March 23, 2026 (Anticipated)
Study Completion Date
March 23, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will have two parts. The main aims are to: check the side effects from mezagitamab. check for long-term side effects from mezagitamab. Before starting the study, participants will be asked to provide a 24-hour urine sample. A few weeks later, if enrolled they will begin receiving a subcutaneous injection (under the skin) of mezagitamab once a week for 8 weeks then once every 2 weeks for 16 weeks. When treatment has ended, there will be a 24-week follow-up period. Participants who receive benefit from the treatment may continue in the second part of the study where they will be monitored for up to 96 weeks and possibly retreated for another 24 weeks.
Detailed Description
The drug being tested in this study is called mezagitamab. Mezagitamab is being tested for the first time in this patient population and might help to treat people who have Primary Immunoglobulin (IgA) Nephropathy. This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of mezagitamab in combination with stable background therapy. The study will enroll approximately 16 participants. The study will consist of 2 key components: a main study and a long-term extension (LTE) study, which includes an observation period and a retreatment period. The observation period of the LTE study is a non-interventional study segment and the retreatment period of the LTE study consists of a redosing period in which participants will be administered mezagitamab at the same dose level as in the main study. Only participants who have a positive outcome during the main study will enter LTE study. Participants will be enrolled to the following cohort: • Mezagitamab This multi-center trial will be conducted in the United States, Europe, and Asia Pacific. The overall time to participate in this study is approximately 154 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Disease, Glomerulonephritis
Keywords
Drug Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mezagitamab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Mezagitamab
Other Intervention Name(s)
TAK-079
Intervention Description
TAK-079 subcutaneous injection.
Primary Outcome Measure Information:
Title
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
Description
The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Time Frame
Up to Week 48
Title
LTE Observation Period: Percentage of Participants With one or More TEAEs, Grade 3 or Higher TEAEs and SAEs
Description
The severity of TEAEs will be graded using NCI-CTCAE version 5.0.
Time Frame
Up to Week 96
Title
LTE Retreatment Period: Percentage of Participants With one or More TEAEs, SAEs, Grade 3 or Higher TEAEs and AEs leading to Mezagitamab Discontinuation
Description
The severity of TEAEs will be graded using NCI-CTCAE version 5.0.
Time Frame
Retreatment Week 0 to 48
Secondary Outcome Measure Information:
Title
Main Study: Ctrough: Observed Serum Trough Concentrations of Mezagitamab
Time Frame
Week 0 Pre-dose and at multiple time points (up to Week 48)
Title
Main Study: Serum IgA Levels
Time Frame
Week 0 Pre-dose and at multiple time points (up to Week 48)
Title
Main Study: Percent Change From Baseline in Proteinuria Based on Urine Protein to Creatinine Ratio (UPCR)
Description
UPCR is calculated by dividing the concentration of protein (milligram per deciliter [mg/dL]) in urine by the urine creatinine concentration (mg/dL).
Time Frame
Week 36
Title
Main Study: Percentage of Participants Based on Antidrug Antibody (ADA) Levels in Serum
Description
Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.
Time Frame
Up to Week 48
Title
LTE Observation Period: Serum IgA Levels
Time Frame
Week 56 Pre-dose and at multiple time points (up to Week 96)
Title
LTE Observation Period: Percent Change From Baseline in Proteinuria Based on UPCR
Description
UPCR is calculated by dividing the concentration of protein (mg/dL) in urine by the urine creatinine concentration (mg/dL).
Time Frame
Up to Week 96
Title
LTE Observation Period: Percentage of Participants Based on ADA Levels in Serum
Time Frame
Up to Week 96
Title
LTE Retreatment Period: Percentage of Participants Based on ADA Levels in Serum
Description
Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.
Time Frame
Up to Retreatment Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Renal biopsy report supporting diagnosis of primary IgAN or IgA vasculitis-associated nephritis within 10 years prior to the screening visit. 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. Estimated glomerular filtration rate (eGFR) >=45 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) at screening. 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. Exclusion Criteria: Kidney biopsy confirming significant renal disease other than IgAN. Secondary IgAN (such as with significant liver disease, inflammatory bowel disease, and seronegative spondyloarthropathies). Evidence of rapidly progressive glomerulonephritis (loss of >=50 percent (%) of eGFR within 3 months prior to the screening visit). 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. Diagnosis of acute active extrarenal IgA vasculitis (Henoch-Schönlein 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. 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. Use of systemic corticosteroids within 4 months from screening visit or expected use for the duration of the study. 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. 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. 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. 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. A positive T-cell interferon-gamma release assay (TIGRA) (result through QuantiFERON-TB Gold test or T-Spot/Elispot) at the screening visit. 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. Inadequate organ and bone marrow function at screening visit. Presence of uncontrolled or New York Heart Association (NYHA 1994) Class 3 or 4 congestive heart failure at the screening visit. Uncontrolled diabetes manifested by glycosylated hemoglobin (HbA1c) >8% at the screening visit. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Amicis Research Center - Northridge - Nordhoff
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
Boise Kidney and Hypertension Institute - Frenova
City
Nampa
State/Province
Idaho
ZIP/Postal Code
83687
Country
United States
Facility Name
NorthShore University HealthSystem
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Core Research Group
City
Milton
State/Province
Queensland
ZIP/Postal Code
4064
Country
Australia
Facility Name
Monash Health, Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Beijing Friendship Hospital,Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Guangdong Provincial Peoples Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xian
State/Province
Shaanxi
ZIP/Postal Code
710061
Country
China
Facility Name
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
City
Szeged
State/Province
Csongrad
ZIP/Postal Code
6720
Country
Hungary
Facility Name
Semmelweis Egyetem
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
City
Brescia
State/Province
Lombardia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Kasugai Municipal Hospital
City
Kasugai-Shi
State/Province
Aiti
ZIP/Postal Code
486-0804
Country
Japan
Facility Name
Fujita Health University Hospital
City
Toyoake-shi
State/Province
Aiti
ZIP/Postal Code
470-1192
Country
Japan
Facility Name
Hiroshima University Hospital
City
Hiroshima-shi
State/Province
Hirosima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Sapporo City General Hospital
City
Sapporo-shi
State/Province
Hokkaido
ZIP/Postal Code
060-8604
Country
Japan
Facility Name
Seoul National University Hospital
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Suwon-si
ZIP/Postal Code
16499
Country
Korea, Republic of
Facility Name
National University Hospital- Singapore
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron - PPDS
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Fundacio Puigvert
City
Barcelona
ZIP/Postal Code
8025
Country
Spain
Facility Name
Taipei Medical University Shuang Ho Hospital
City
New Taipei City
ZIP/Postal Code
23561
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Leicester General Hospital
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE5 4PW
Country
United Kingdom
Facility Name
Hull Royal Infirmary
City
Hull
ZIP/Postal Code
HU3 2JZ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/7f3e474338f74829?idFilter=%5B%22TAK-079-1006%22%5D
Description
To obtain more information on the study, click here/on this link

Learn more about this trial

A Study of Mezagitamab in Adults With Primary Immunoglobulin A Nephropathy Receiving Stable Background Therapy

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