In this study, researchers will learn more about the use of felzartamab in participants with primary membranous nephropathy, also known as PMN. In people with PMN, autoantibodies build up in the glomeruli of the kidney. Antibodies are proteins that help the body fight off infection. An autoantibody is a type of antibody that mistakenly targets and attacks the body's own tissues. Glomeruli are the filters of the kidney that remove waste and extra fluid from the body. In PMN, the build-up of autoantibodies in the glomeruli causes damage to the kidneys. Kidney damage can lead to too much protein and blood leaking into the urine. High levels of protein in the urine, called proteinuria, are common in people with PMN. Symptoms of PMN can include swelling in the legs and body, tiredness, and high blood pressure. If left untreated, PMN can eventually lead to kidney failure. In this study, researchers will learn more about how a study drug called felzartamab affects people with PMN. Felzartamab is a monoclonal antibody, which means it is an antibody made in a laboratory. Felzartamab can target immune cells that produce autoantibodies, helping to lower their buildup in the kidneys. The main goal of this study is to compare how felzartamab works compared to a drug called tacrolimus. Tacrolimus is another drug given to people with PMN and kidney disease. The main question that researchers want to answer is: * How many participants achieve a complete response after 104 weeks of treatment? * A complete response means that their urine protein levels decrease to a low level and their kidney function remains stable. Researchers will also learn about: * How long it takes before the participants' disease gets worse * How long the participants' urine protein levels stay low * How many participants develop antibodies against felzartamab in the blood? * How many participants achieve a complete response after 76 weeks of treatment * How many participants have medical problems during the study * How felzartamab is processed by the body * How felzartamab affects participants' tiredness and overall physical health The study will be done as follows: * Participants will be screened to check if they can join the study. This may take up to 42 days. * Participants will be randomized to receive either felzartamab as intravenous (IV) infusions or tacrolimus, taken orally as tablets. * If participants have worsening kidney function or worsening proteinuria, or if their PMN relapses, or if they show no signs of improvement in their PMN, they will have a chance to receive rescue treatment. * If a participant stops treatment early, there will be follow-up visits every 12 weeks until they reach Week 104. * In total, participants will have up to 23 study visits. Participants who do not need rescue treatment will stay in the study for up to 104 weeks. Participants who need rescue treatment will stay in the study for up to 156 weeks.
The primary objective of the study is to assess the efficacy of felzartamab compared to tacrolimus in participants with PMN in achieving complete remission (CR) of proteinuria. The secondary objectives of the study are to evaluate the efficacy of felzartamab through additional clinical endpoints and timepoints, to assess the impact of felzartamab on serum anti-phospholipase A2 receptor (PLA2R) antibodies and patient-reported outcomes, and to assess the safety, pharmacokinetics (PK) and immunogenicity of felzartamab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
180
Administered intravenously
Administered orally
Administered intravenously and orally
Apogee Clinical Research, LLC
Huntsville, Alabama, United States
RECRUITINGThe Nephrology Group, Inc. - Fresno
Fresno, California, United States
RECRUITINGAcademic Medical Research Institute
Los Angeles, California, United States
RECRUITINGUCSF Medical Center
San Francisco, California, United States
Percentage of Participants who Achieve Complete Remission (CR) at Week 104
Time frame: Week 104
Percentage of Participants who Achieve Overall Remission (OR), Defined as CR or Partial Remission (PR) at Week 104
Time frame: Week 104
Percentage of Participants who Achieve CR at Week 76
Time frame: Week 76
Duration of CR
Time frame: Baseline up to week 156
Percentage of Participants With a Baseline Anti-Phospholipase A2 Receptor (PLA2R) Autoantibody Titer Greater Than 50 Relative Unit per Milliliter (RU/mL) who Achieve an OR at Week 76 and at Week 104
Time frame: Weeks 76 and 104
Time to Disease Worsening
Time frame: Baseline up to week 156
Time to a Sustained Reduction in eGFR of ≥ 30% From Baseline
Time frame: Baseline up to week 104
Absolute Change in Anti-PLA2R Autoantibody Titer in Participants Positive for Anti-PLA2R at Baseline
Time frame: Baseline up to week 156
Change From Baseline in the Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Scale at Week 104
Time frame: Week 104
Change From Baseline in PROMIS Global Assessment of Physical Health Scale at Week 104
Time frame: Week 104
Number of Participants With Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and Adverse Events of Special Interest (AESIs)
Time frame: From first dose of study drug up to end of follow-up (up to week 156)
Felzartamab Serum Concentrations Over Time
Time frame: Predose and at multiple timepoints post dose up to week 156
Number of Participants With Anti-Drug Antibodies (ADAs) Against Felzartamab
Time frame: Predose and at multiple timepoints post dose up to week 156
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Henry Ford Hospital- A-Basement Research Pharmacy
Detroit, Michigan, United States
RECRUITINGElixia Health - Michigan Kidney Consultants, LLC - Elixia - PPDS
Pontiac, Michigan, United States
COMPLETEDJames J Peters Veterans Administration Medical Center - NAVREF - PPDS
The Bronx, New York, United States
RECRUITINGECU Physicians Nephrology and Hypertension
Greenville, North Carolina, United States
RECRUITINGKnoxville Kidney Center, PLLC
Knoxville, Tennessee, United States
RECRUITINGNephrotex Research Group
Dallas, Texas, United States
RECRUITING...and 79 more locations