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

Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05174221
• Other study ID #: TAK-079-1006
• Secondary ID: 2021-005023-20jR
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 9, 2022
• Est. completion date: March 23, 2026

Study information

• Verified date: December 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: March 23, 2026
• Est. primary completion date: March 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis
• Kidney Disease
• Kidney Diseases

Intervention

Drug:
• Mezagitamab
TAK-079 subcutaneous injection.

Locations

Country	Name	City	State
Australia	Monash Health, Monash Medical Centre	Clayton	Victoria
Australia	Core Research Group	Milton	Queensland
Australia	Royal Melbourne Hospital	Parkville	Victoria
China	Beijing Friendship Hospital,Capital Medical University	Beijing	Beijing
China	Guangdong Provincial Peoples Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xian	Shaanxi
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged	Csongrad
Italy	ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia	Brescia	Lombardia
Japan	Hiroshima University Hospital	Hiroshima-shi	Hirosima
Japan	Kasugai Municipal Hospital	Kasugai-Shi	Aiti
Japan	Sapporo City General Hospital	Sapporo-shi	Hokkaido
Japan	Fujita Health University Hospital	Toyoake-shi	Aiti
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Ajou University Hospital	Suwon-si
Singapore	National University Hospital- Singapore	Singapore
Spain	Fundacio Puigvert	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Taiwan	Taipei Medical University Shuang Ho Hospital	New Taipei City
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Hull Royal Infirmary	Hull
United Kingdom	Leicester General Hospital	Leicester	Leicestershire
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	Boise Kidney and Hypertension Institute - Frenova	Nampa	Idaho
United States	Amicis Research Center - Northridge - Nordhoff	Northridge	California

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Australia,  China,  Hungary,  Italy,  Japan,  Korea, Republic of,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to Week 48
Primary	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.	Up to Week 96
Primary	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.	Retreatment Week 0 to 48
Secondary	Main Study: Ctrough: Observed Serum Trough Concentrations of Mezagitamab		Week 0 Pre-dose and at multiple time points (up to Week 48)
Secondary	Main Study: Serum IgA Levels		Week 0 Pre-dose and at multiple time points (up to Week 48)
Secondary	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).	Week 36
Secondary	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.	Up to Week 48
Secondary	LTE Observation Period: Serum IgA Levels		Week 56 Pre-dose and at multiple time points (up to Week 96)
Secondary	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).	Up to Week 96
Secondary	LTE Observation Period: Percentage of Participants Based on ADA Levels in Serum		Up to Week 96
Secondary	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.	Up to Retreatment Week 48

External Links

•   To obtain more information on the study, click here/on this link