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

Sponsor
Takeda (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05174221
Collaborator
(none)
16
Enrollment
30
Locations
1
Arm
42.1
Anticipated Duration (Months)
0.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
16 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Sep 20, 2022
Anticipated Primary Completion Date :
Mar 23, 2026
Anticipated Study Completion Date :
Mar 23, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Mezagitamab
TAK-079 subcutaneous injection.
Other Names:
  • TAK-079

    		•

    Outcome Measures

    Primary Outcome Measures

    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 [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 [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 [Retreatment Week 0 to 48]

      The severity of TEAEs will be graded using NCI-CTCAE version 5.0.

    Secondary Outcome Measures

    1. Main Study: Ctrough: Observed Serum Trough Concentrations of Mezagitamab [Week 0 Pre-dose and at multiple time points (up to Week 48)]

    2. Main Study: Serum IgA Levels [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) [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 [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 [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 [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 [Up to Week 96]

    8. LTE Retreatment Period: Percentage of Participants Based on ADA Levels in Serum [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    1. 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.

    2. 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.

    3. 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.

    4. A positive T-cell interferon-gamma release assay (TIGRA) (result through QuantiFERON-TB Gold test or T-Spot/Elispot) at the screening visit.

    5. 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.

    6. Inadequate organ and bone marrow function at screening visit.

    7. Presence of uncontrolled or New York Heart Association (NYHA 1994) Class 3 or 4 congestive heart failure at the screening visit.

    8. Uncontrolled diabetes manifested by glycosylated hemoglobin (HbA1c) >8% at the screening visit.

    9. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Amicis Research Center - Northridge - Nordhoff Northridge California United States 91324-3528
    2 Boise Kidney and Hypertension Institute - Frenova Nampa Idaho United States 83687-9289
    3 NorthShore University HealthSystem Evanston Illinois United States 60201-1700
    4 Core Research Group Milton Queensland Australia 4064
    5 Monash Health, Monash Medical Centre Clayton Victoria Australia 3168
    6 Royal Melbourne Hospital Parkville Victoria Australia 3050
    7 Regionaal Ziekenhuis Jan Yperman VZW Ieper West-Vlaanderen Belgium 8900
    8 AZ Delta Roeselare West-Vlaanderen Belgium 8800
    9 Beijing Friendship Hospital,Capital Medical University Beijing Beijing China 100050
    10 Guangdong Provincial People's Hospital Guangzhou Guangdong China 510080
    11 The First Affiliated Hospital of Xi'an Jiaotong University Xian Shaanxi China 710061
    12 Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Szeged Csongrad Hungary 6720
    13 Semmelweis Egyetem Budapest Hungary 1083
    14 ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia Brescia Lombardia Italy 25123
    15 ASST di Monza - Azienda Ospedaliera San Gerardo Monza Lombardia Italy 20900
    16 Kasugai Municipal Hospital Kasugai-Shi Aiti Japan 486-0804
    17 Fujita Health University Hospital Toyoake-shi Aiti Japan 470-1192
    18 Hiroshima University Hospital Hiroshima-shi Hirosima Japan 734-8551
    19 Sapporo City General Hospital Sapporo-shi Hokkaido Japan 060-8604
    20 Ajou University Hospital Suwon-si Gyeonggido Korea, Republic of 16499
    21 Seoul National University Hospital Seoul Seoul Teugbyeolsi Korea, Republic of 3080
    22 University Clinical Center of Serbia - PPDS Belgrade Serbia 11000
    23 University Clinical Center Nis Nis Serbia 18 000
    24 National University Hospital Singapore Singapore 119074
    25 Hospital Universitario Marques de Valdecilla Santander Cantabria Spain 39008
    26 Hospital Universitario Vall d'Hebron - PPDS Barcelona Spain 8035
    27 Taipei Medical University Shuang Ho Hospital New Taipei City Taiwan 23561
    28 National Taiwan University Hospital Taipei Taiwan 100
    29 Leicester General Hospital Leicester Leicestershire United Kingdom LE5 4PW
    30 Hull Royal Infirmary Hull United Kingdom HU3 2JZ

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT05174221
    Other Study ID Numbers:
    • TAK-079-1006
    • 2021-005023-20
    • jRCT2011220009
    First Posted:
    Dec 30, 2021
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Keywords provided by Takeda
    Drug Therapy
    Additional relevant MeSH terms:
    Kidney Diseases

    Study Results

    No Results Posted as of Aug 18, 2022