Clinical trial NCT05174221: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Kidney Disease
Glomerulonephritis
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-12-30
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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/L) 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.

Primary outcomes:
measure: 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
timeFrame: Up to Week 48
measure: LTE Observation Period: Percentage of Participants With one or More TEAEs, Grade 3 or Higher TEAEs and SAEs
timeFrame: Up to Week 96
measure: LTE Retreatment Period: Percentage of Participants With one or More TEAEs, SAEs, Grade 3 or Higher TEAEs and AEs leading to Mezagitamab Discontinuation
timeFrame: Retreatment Week 0 to 48
Secondary outcomes:
measure: Main Study: Ctrough: Observed Serum Trough Concentrations of Mezagitamab
timeFrame: Week 0 Pre-dose and at multiple time points (up to Week 48)
measure: Main Study: Serum IgA Levels
timeFrame: Week 0 Pre-dose and at multiple time points (up to Week 48)
measure: Main Study: Percent Change From Baseline in Proteinuria Based on Urine Protein to Creatinine Ratio (UPCR)
timeFrame: Week 36
measure: Main Study: Percentage of Participants Based on Antidrug Antibody (ADA) Levels in Serum
timeFrame: Up to Week 48
measure: LTE Observation Period: Serum IgA Levels
timeFrame: Week 56 Pre-dose and at multiple time points (up to Week 96)
measure: LTE Observation Period: Percent Change From Baseline in Proteinuria Based on UPCR
timeFrame: Up to Week 96
measure: LTE Observation Period: Percentage of Participants Based on ADA Levels in Serum
timeFrame: Up to Week 96
measure: LTE Retreatment Period: Percentage of Participants Based on ADA Levels in Serum
timeFrame: Up to Retreatment Week 48
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Amicis Research Center - Northridge - Nordhoff
state: California
city: Nampa
country: United States
facility: Boise Kidney and Hypertension Institute - Frenova
state: Idaho
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Milton
country: Australia
facility: Core Research Group
state: Queensland
city: Clayton
country: Australia
facility: Monash Health, Monash Medical Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Beijing
country: China
facility: Beijing Friendship Hospital,Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Xian
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
state: Csongrad
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
state: Lombardia
city: Kasugai-Shi
country: Japan
facility: Kasugai Municipal Hospital
state: Aiti
city: Toyoake-shi
country: Japan
facility: Fujita Health University Hospital
state: Aiti
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hirosima
city: Sapporo-shi
country: Japan
facility: Sapporo City General Hospital
state: Hokkaido
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
city: Singapore
country: Singapore
facility: National University Hospital- Singapore
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Fundacio Puigvert
city: New Taipei City
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: Leicestershire
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: