Resumen

La nefropatía por inmunoglobulina A (NIgA) es una enfermedad renal. Se produce cuando el sistema inmunitario del organismo genera grupos de proteínas (llamados complejos inmunes) que se acumulan en los riñones causando inflamación. Con el tiempo, esta inflamación puede provocar daño renal y que los riñones dejen de funcionar correctamente. El objetivo principal de este estudio es evaluar la eficacia de mezagitamab para modificar los niveles de proteína en orina (proteinuria) en comparación con placebo en adultos con NIgA primaria. El placebo tiene el mismo aspecto que el medicamento pero no contiene ningún principio activo. Otros objetivos son evaluar la seguridad de mezagitamab y cuán bien la toleran los participantes con NIgA primaria en comparación con placebo, así como determinar si mezagitamab logra mantener la función renal a largo plazo en comparación con placebo. Los participantes serán asignados a 1 de los 2 grupos de tratamiento: el grupo principal y el grupo abierto. En el grupo principal, los participantes serán asignados al azar a 1 de los 2 grupos de tratamiento (ya sea mezagitamab o placebo) en una proporción de 2:1. Esto significa que de cada 3 participantes, 2 recibirán mezagitamab y 1 recibirá placebo. Los participantes recibirán mezagitamab o placebo durante casi medio año en dos ciclos de 1 año cada uno. Serán observados durante otro medio año en cada ciclo de 1 año y tendrán controles aproximadamente una vez por mes durante ese tiempo. En el grupo abierto, un pequeño número de participantes con niveles más bajos de proteína en orina o con riñones que no filtran bien la sangre recibirá tratamiento con mezagitamab. Esto incluirá participantes que hayan recibido previamente mezagitamab en otro estudio, TAK-079-1006. Todos los participantes recibirán mezagitamab de la misma manera que quienes lo reciben en el grupo principal. Durante el estudio, los participantes visitarán su centro clínico del estudio en varias ocasiones.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

To be eligible to participate in this trial, an individual must meet all the following criteria:
Either UPCR greater than or equal to (≥) 0.8 gram per gram (g/g) or urine protein excretion (UPE) ≥1 grams per day (g/day), calculated from a 24-hour urine collection during the screening period (only applicable for the main group).
eGFR greater than (\>)30 milliliters per minute per 1.73 meter square (mL/min/1.73m\^2) at screening based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (only applicable for the main group).
No prior exposure to anti- cluster of differentiation 38 (CD38) therapy period (only applicable for the main group).
The participant is at least aged 18 years or the local legal age if greater than 18 years, inclusive.
The participant (and the participant's legally acceptable representative, if applicable per local regulations or determination) has provided informed consent (that is, in writing, documented via a signed and dated informed consent form \[ICF\]) and any required privacy authorization before the initiation of any clinical trial procedures.
Renal biopsy report supporting diagnosis of primary IgAN within 10 years before signing informed consent for the clinical trial. The redacted report must be made available for review. A renal biopsy may be performed during screening.
Participants must be on stable renin-angiotensin-aldosterone system (RAAS) inhibitor therapy with an angiotensin-converting enzyme inhibitor (ACE-I) and/or angiotensin receptor blocker (ARB) or endothelin receptor antagonist (ERA) or mineralocorticoid receptor antagonist (MRA) agent for at least 12 weeks before signing the ICF with dosing at the maximally tolerated or labeled dose as determined by the investigator, with the intent to continue stable dosing during the clinical trial. Those intolerant of RAAS inhibitor therapy are potentially eligible after consultation with the medical monitor. Intolerance is defined as a documented side effect causing discontinuation of the therapy.
Women of childbearing potential who are not pregnant during screening (confirmed by negative serum human chorionic gonadotropin \[hCG\]) and on Visit 1 before first dose of trial intervention (confirmed by negative urine pregnancy test).
Any one of the following (only applicable for the open-label cohort):
Participants in Study TAK-079-1006 who completed the Week 96 visit or the retreatment period with either UPCR \>0.5 g/g or UPE \>0.5 g/d calculated from a 24-hour urine collection during the screening period and eGFR \>30 mL/min/1.73m\^2 at screening based on the CKD-EPI formula.
UPCR \<0.8 g/g and UPE ≥0.75 and \<1.0 g/day, by 24-hour urine collection during the screening period and eGFR \> 30 mL/min/1.73m\^2 at screening based on the CKD-EPI formula.
UPCR ≥ 0.8 g/g or UPE ≥ 1.0 g/d by 24-hour urine collection during the screening period and eGFR ≥25 and ≤30 mL/min/1.73m\^2 at screening based on the CKD-EPI formula.

Criterios de exclusión

An individual who meets any of the following criteria will be excluded from participation in this trial:
Kidney biopsy exhibiting significant concomitant renal disease other than IgAN (for example, diabetic nephropathy, lupus nephritis, minimal change disease).
Secondary IgAN (such as with significant liver disease, immunoglobulin A (IgA) vasculitis, inflammatory bowel disease, and seronegative spondyloarthropathies).
Evidence of rapidly progressive glomerulonephritis (loss of ≥50% of eGFR within 3 months before the signing of the ICF).
Diagnosis of nephrotic syndrome defined as 24-hour proteinuria \>3.5 g/day or hypoalbuminemia (\<3.0 grams per deciliter \[g/dL\]) with or without peripheral edema.
Renal or other organ transplantation prior to or expected during the clinical trial.
Treatment with oral immunosuppressive agents (including cyclophosphamide, mycophenolate mofetil, cyclosporine, azathioprine, calcineurin inhibitors) or biologic therapy for immunomodulation (including immunomodulatory monoclonal or polyclonal antibodies) within 6 months (both B-cell and non-B-cell directed agents) before signing of the ICF.
If the participant has received anti-CD20 treatment, the participant is excluded if either of the following apply:
The last dose was received within 6 months before the signing of the ICF.
The last dose was received between 6 and 12 months before the signing of the ICF and the participant has a CD19+ count below the lower limit of normal.
Note: Participants who have received the last dose of anti-CD20 treatment \>12 months before the signing of the ICF are not excluded from clinical trial participation based on this criterion and are not required to undergo CD19+ testing.
Use of systemic corticosteroids at an average dose of 40 milligrams (mg) prednisone equivalent or higher for more than 14 days within 4 months of the screening visit, or use of oral budesonide delayed release capsules within 1 year of the screening visit.
The participant has received a live or live-attenuated vaccine within 4 weeks before signing the ICF or has any live or live-attenuated vaccine planned during the clinical trial.
Participation in any other investigational drug trial (including vaccine trial) with receipt of at least 1 dose of investigational drug, or has been exposed to another investigational agent within 4 weeks or 5 half-lives, whichever is longer, before Visit 1.
The participant has active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
The participant has had any of the following types of infections within the specified timeframes where applicable:
Active bacterial, viral, fungal infection (except for the common cold and onychomycosis), or any other serious infection within 2 weeks of signing the ICF. Any anti-infective course for infection must be completed at least 2 weeks before Visit 1.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infection within 4 weeks of signing the ICF.
Opportunistic infection or treatment for an opportunistic infection lesser than or equal to (≤)12 weeks before signing the ICF.
In the opinion of the investigator, the participant is currently experiencing any medical condition that might interfere with participation in the trial (for example, significant ocular, cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurologic, malignancy, infectious disease, immunodeficiency, or alcohol and drug abuse), that poses an added risk for the participant or could confound the assessment of trial results.
In the opinion of the investigator, the participant has a serious medical or psychiatric illness that could potentially interfere with the completion of treatment.
The participant has a history of major surgery within 3 months before screening (or longer, at the discretion of the investigator); or, either has a planned tonsillectomy or underwent a tonsillectomy within 6 months before screening.
Note: Major surgery typically requires at least 1 night in the hospital.
History of malignancy (including myelodysplastic syndrome) within 5 years of signing the ICF, except for adequately treated non-melanoma skin cancer, superficial bladder cancer, and curatively treated cervical carcinoma-in-situ.
The participant has a history of a severe allergic or anaphylactic reaction to recombinant proteins or excipients used in the mezagitamab or placebo formulation.
The participant has (1) been diagnosed with or has suspected chronic obstructive pulmonary disease (COPD) or asthma and (2) has a prebronchodilatory forced expiratory volume in 1 second (FEV1) \<50% of predicted normal at screening.
The participant is capable of breastfeeding but does not agree to forego breastfeeding from first dose of investigational medicinal product (IMP) through 30 days after the last dose of IMP.
The participant is an individual with potential for pregnancy but does not agree to use at least 1 form of highly effective contraception and 1 barrier method of contraception (preferably male condom) when engaging in heterosexual sex for the protocol specified duration after the last dose of IMP.
The participant is a sexually active, non-sterilized individual who produces sperm but does not agree to use a barrier method (preferably male condom) combined with at least 1 form of highly effective contraception for any partner(s) with potential for pregnancy when engaging in heterosexual sex for the protocol specified duration after the last dose of IMP.
In the investigator's opinion, the participant (and the participant's legally acceptable representative, if applicable per local regulations or determination) is unwilling and/or unable to understand and fully comply with clinical trial procedures and requirements (including digital tools and applications).

Ubicaciones

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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RECRUITING

Framingham Centro Medico

Buenos Aires, La Plata, Argentina

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RECRUITING

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, Argentina

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RECRUITING

Clinica Privada Velez Sarsfield

Córdoba, Argentina

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RECRUITING

Ensayo clínico de Fase 3, multicéntrico, aleatorizado, doble ciego y controlado con placebo para evaluar la eficacia y seguridad de mezagitamab (TAK-079) en participantes con nefropatía por IgA primaria en combinación con terapia de base estable

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Mezagitamab

Placebo

Ubicaciones

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Framingham Centro Medico

Hospital Britanico de Buenos Aires

Clinica Privada Velez Sarsfield

Patrocinadores

Contactos

Takeda Contact