Immunoglobulin A Nephropathy (IgAN)
Conditions
Brief summary
In this study, researchers will learn more about the use of felzartamab in participants with immunoglobulin A nephropathy (IgAN). This study will focus on participants who have protein in their urine (proteinuria) as a result of damaged kidneys. The main goal of the study is to learn about the effect felzartamab has on proteinuria. The main question that researchers want to answer is: • How much does the amount of protein in the urine change from the start of the study to Week 36? Researchers will learn about the effect felzartamab has on the kidneys' ability to filter blood. They will also learn more about the safety of felzartamab and how it is processed by the body. The study will be done as follows: * Participants will be screened to check if they can join the study. * Participants will be randomized to receive either felzartamab or a placebo. A placebo looks like the study drug but contains no real medicine. * Neither the researchers nor the participants will know what the participants will receive. * Participants will receive felzartamab or placebo as intravenous (IV) infusions. The treatment period will last 24 weeks. * Afterwards, participants will enter a follow-up period which will last 80 weeks. * In total, participants will have 17 study visits. Participants will stay in the study for about 2 years.
Detailed description
The primary objective of the study is to evaluate the efficacy of felzartamab compared to placebo on proteinuria in participants with Immunoglobulin A nephropathy (IgAN). The main secondary objective of the study is to evaluate the efficacy of felzartamab compared to placebo on kidney functions in participants with IgAN. The additional secondary objectives are to evaluate the efficacy of felzartamab compared to placebo on additional clinical endpoints and to assess the pharmacokinetics (PK) and immunogenicity of felzartamab.
Interventions
DRUGFelzartamab
Administered IV
DRUGPlacebo
Administered IV
Sponsors
Biogen
Human Immunology Biosciences, Inc. (HI-Bio)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Biopsy-confirmed diagnosis of IgAN within the past 10 years prior to signature of the informed consent form (ICF). For participants with diabetes mellitus type 2, biopsy confirmation of IgAN diagnosis must be done within the past 24 months prior to signing the ICF. * An eGFR ≥ 30 mL/min/1.73m\^2 at Screening as calculated using the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine formula. An eGFR of ≥ 20 and \< 30 mL/min/1.73m\^2 is acceptable for the cohorts 3 and 4. * Proteinuria of ≥ 1.0 gram per day (g/day) or UPCR ≥0.8 gram per gram (g/g) as assessed by an adequate 24-hour urine collection. * Clinically stable on a maximally tolerated dose or maximally approved dose of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) for at least 12 weeks prior to Screening, or intolerant of ACEI or ARB. If intolerant, this must be discussed with the Medical Monitor prior to randomization. Participants may also be using sodium-glucose cotransporter-2 inhibitors (SGLT2is), endothelin receptor antagonists (ERAs) approved for the treatment of IgAN, dual endothelin angiotensin receptor antagonist (DEARAs) approved for the treatment of IgAN, and/or mineralocorticoid receptor antagonists (MRAs) as long as the dose is stable for at least 12 weeks prior to Screening. Participants should remain on stable doses of these background medications for the duration of the study. Once the ICF is signed and thereafter, the doses cannot be changed during the study nor the drugs discontinued except if deemed related to an AE. Participants using sparsentan will not be permitted to use simultaneous ACEI or ARB medication. Key
Exclusion criteria
* Secondary forms of IgAN, indicated by the presence of any other systemic disease potentially leading to IgA deposits as determined by the Investigator. * History of rapidly progressive variant of IgAN, defined as eGFR loss by \> 50% per 3 months and not explained by changes in renin-angiotensin system (RAS) blockade or other factors. * Nephrotic syndrome presumed to be due to minimal change disease (MCD) variant. * Concomitant other progressive glomerulonephritis or non-immunologic glomerular disease such as diabetic nephropathy. * Type 2 diabetes mellitus with Hemoglobin A1c (HbA1c) \> 8% at Screening, or evidence of diabetic nephropathy on biopsy, history of diabetic microvascular or macrovascular disease (eg, diabetic retinopathy, peripheral neuropathy). * Any diagnosed or suspected immunosuppressed or immunodeficient state such as asplenia, human immunodeficiency virus (HIV), primary immunodeficiencies, organ or bone marrow transplantation, with the exception of corneal transplants. * Previously treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure (\> 7.5 milligrams per deciliter \[mg/d\] prednisone/prednisolone equivalent) within 4 months (or 12 months for rituximab) prior to Screening. * Participants currently treated with oral budesonide. Participants who have stopped this therapy ≥ 4 months prior to Screening may be eligible. * Active clinically significant infections, known history of recurrent clinically significant infection, or Screening laboratory evidence consistent with an active infection, or IV anti-infectives (antibacterials, antiviral or antifungals). Participants with a history of opportunistic infections are excluded. * Hypogammaglobulinemia: Serum Immunoglobin G (IgG) \< 6.0 gram per litre (g/L), at Screening. Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Proteinuria as Measured by the Urine Protein: Creatinine Ratio (UPCR) | Baseline up to Week 36 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Values Calculated Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation | Baseline up to Week 104 | — |
| Percentage of Participants Achieving Complete Response (CR) | Baseline up to Week 104 | CR is defined as a UPCR value (based on 24-hour urine collection) of \< 0.5 gram per gram (g/g), a reduction in UPCR of ≥ 50%, and a stable eGFR (decrease from baseline in eGFR of ≤ 25%). |
| Percentage of Participants who Progressed to Kidney Malfunction | Baseline up to Week 104 | The percentage of participants progressing to kidney malfunction will be reported based on one of the following, 1. ≥ 40% Reduction in eGFR Sustained for ≥ 30 Days, 2. eGFR \<15 mL/min/1.73m\^2 for ≥ 30 Days, 3. Undergoing Dialysis for ≥ 30 Days, 4. Undergoing Kidney Transplantation, 5. Died From Kidney Failure |
| Percentage of Participants Requiring Rescue Therapy | Baseline up to Week 104 | — |
| Change From Baseline in eGFR Values Calculated Using the CKD-EPI Creatinine Equation | Baseline up to Week 52 | — |
| Felzartamab Serum Concentrations Over Time | Predose and at multiple timepoints postdose up to Week 36 | — |
| Number of Participants with Anti-Drug Antibodies (ADAs) Against Felzartamab | Baseline up to Week 104 | — |
| Percentage of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) | Baseline up to Week 104 | — |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs Abnormalities | Baseline up to Week 104 | — |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities | Baseline up to Week 104 | — |
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Abnormalities | Baseline up to Week 104 | — |
| Number of Participants With Clinically Significant Change From Baseline in Physical Examinations Abnormalities | Baseline up to Week 104 | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Czechia, France, Germany, Greece, India, Italy, Japan, Malaysia, New Zealand, Philippines, Poland, Portugal, Puerto Rico, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTUS Biogen Clinical Trial Center
CONTACTGlobal Biogen Clinical Trial Center
STUDY_DIRECTORMedical Director
Biogen
Outcome results
None listed