A Study of Guselkumab in Participants With Active Lupus Nephritis

NCT ID: NCT04376827

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2023-02-01

Brief Summary

The purpose of this study is to evaluate the efficacy of guselkumab in participants with active lupus nephritis (LN).

Detailed Description

Guselkumab is a monoclonal antibody (mAb) that binds to human interleukin (IL)-23 with high affinity and blocks binding of extracellular IL-23 to cell surface IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent activation and cytokine production. It is used in treatment of plaque psoriasis, psoriatic arthritis, generalized pustular psoriasis, erythrodermic psoriasis. Lupus is a heterogeneous autoimmune disease with lesions confined to skin (cutaneous lupus erythematosus [CLE]) to others that involve 1 or more vital internal organs (systemic lupus erythematosus [SLE]). Renal involvement due to SLE is termed lupus nephritis (LN). There is a high unmet need for new treatment options in LN that are safe and effective, especially new therapies that can provide improved long-term efficacy over currently available therapies. This study will evaluate safety and efficacy of guselkumab added to standard-of-care compared to placebo added to standard-of-care. Total duration of study is up to 68 weeks: a less than or equal to 8 week screening period, a 48 week double-blind treatment period, a 12 week safety follow-up period after last dose. Participants who complete the assessments at Week 52 and have achieved complete renal response (CRR) may have the option to participate in the long-term extension (LTE) of study through Week 152 and the 12-week safety follow-up visit. Hypothesis of this study is that guselkumab plus standard-of-care is superior to placebo plus standard-of-care in participants with active LN as measured by the proportion of participants inducing at least a 50 percentage reduction of proteinuria with protocol specified steroid tapering regimen at Week 24. Safety assessments include Adverse events (AEs), clinical laboratory tests (hematology and chemistry), systolic and diastolic blood pressures over time, monitoring for hypersensitivity reactions, AEs temporally associated with infusion, injection-site reactions, suicidality assessment, and early detection of active tuberculosis (TB).

Conditions

Lupus Nephritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Guselkumab+Standard of Care

Participants will receive guselkumab Dose 1 intravenously (IV) at Weeks 0, 4 and 8 and guselkumab Dose 2 subcutaneous (SC) every 4 weeks (q4w) from Week 12 through Week 48 along with standard-of-care treatment of mycophenolate mofetil (MMF)/mycophenolic acid (MPA) and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the long-term extension (LTE).

Group Type: EXPERIMENTAL

Guselkumab Dose 1

Intervention Type: DRUG

Participants will receive guselkumab Dose 1 via IV administration.

Guselkumab Dose 2

Intervention Type: DRUG

Participants will receive guselkumab Dose 2 via SC route.

Standard-of-care treatment

Intervention Type: DRUG

Participants will receive standard of care treatment including MMF/MPA and glucocorticoids from Week 12 through Week 48.

Placebo+Standard of Care

Participants will receive placebo IV at Weeks 0, 4 and 8 and placebo SC q4w from Week 12 through Week 48 along with standard-of-care treatment of MMF/MPA and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the LTE of the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive placebo IV at Weeks 0, 4 and 8 (that is, 3 IV doses) and placebo SC q4w from Week 12 through Week 48.

Standard-of-care treatment

Intervention Type: DRUG

Participants will receive standard of care treatment including MMF/MPA and glucocorticoids from Week 12 through Week 48.

Interventions

Guselkumab Dose 1

Participants will receive guselkumab Dose 1 via IV administration.

Intervention Type: DRUG

Placebo

Participants will receive placebo IV at Weeks 0, 4 and 8 (that is, 3 IV doses) and placebo SC q4w from Week 12 through Week 48.

Intervention Type: DRUG

Guselkumab Dose 2

Participants will receive guselkumab Dose 2 via SC route.

Intervention Type: DRUG

Standard-of-care treatment

Participants will receive standard of care treatment including MMF/MPA and glucocorticoids from Week 12 through Week 48.

Intervention Type: DRUG

Other Intervention Names

CNTO 1959; CNTO1959

Eligibility Criteria

Inclusion Criteria

• At screening and randomization, must be receiving oral glucocorticoids at minimum prednisone equivalent dose of 10 milligrams per day (mg/day) and maximum 1 mg/kg/day or less than or equal to (<=) 60 mg/day, whichever is lower. Treated for greater than or equal to (>=) 6 weeks with stable dosing >=2 weeks before randomization
• If receiving angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blockers (ARB), a stable dose for at least 2 weeks prior to randomization
• Positive antinuclear antibody (ANA; >= 1:80 titer by central laboratory test) or anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies (>=30 international units per milliliter ([U/mL] by central laboratory test) detected at screening
• Kidney biopsy documentation of active International Society of Nephrology (ISN)/Renal Pathology Society (RPS) proliferative nephritis: Class III-IV (with or without class V membranous nephritis) within the last 6 months prior to screening or performed during screening
• Urine Protein to Creatinine Ratio (UPCR) >= 1.0 milligram/milligram (mg/mg) assessed on 2 first morning urine void specimens during screening. These 2 specimens do not need to be on consecutive days, however, 2 samples must be tested with UPCR >= 1.0 mg/mg in a row. The UPCR requirement must be met after at least 8 weeks of mycophenolate mofetil (MMF)/mycophenolic acid (MPA) treatment, and after stable glucocorticoid dosing is achieved at the dose intended at time of randomization

Exclusion Criteria

• Comorbidities (other than lupus nephritis [LN], example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months
• Has other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), RA/lupus overlap, psoriasis, Crohn's disease, or active Lyme disease
• Received PO (orally) or intravenously (IV) cyclophosphamide within 3 months prior to randomization
• History of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening
• History of being human immunodeficiency virus (HIV) antibody-positive, or tests positive for HIV at screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Medvin Clinical Research

Covina, California, United States

UC San Diego

La Jolla, California, United States

Academic Medical Research Institute

Los Angeles, California, United States

University of Colorado Denver

Aurora, Colorado, United States

University of Florida College of Medicine

Gainesville, Florida, United States

NYU Langone Ambulatory Care Brooklyn Heights

Brooklyn, New York, United States

The Feinstein Institute for Medical Research

Manhasset, New York, United States

Med Research, Inc.

El Paso, Texas, United States

Centro Médico Reumatológico (OMI)

Buenos Aires, , Argentina

Hospital Ramos Mejia

Caba, , Argentina

ARCIS Salud SRL Aprillus asistencia e investigacion

CABA, , Argentina

Instituto Medico Strusberg SA

Córdoba, , Argentina

Clinica Privada Velez Sarsfield

Córdoba, , Argentina

Instituto de Reumatologia - Ir Medical Center S.A.

Mendoza, , Argentina

Instituto Médico de la Fundación de Estudios Clínicos (ECLIN)

Rosario, , Argentina

Centro de Investigaciones Medicas Tucuman

San Miguel de Tucumán, , Argentina

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, , Mexico

Centro de Investigacion y Tratamiento Reumatologico S C

Mexico City, , Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, , Mexico

Unidad Reumatologica las Americas S.C.P.

Mérida, , Mexico

Consultorio de Reumatologia

México, , Mexico

Unidad de Investigaciones Reumatologicas A.C

San Luis Potosí City, , Mexico

Uniwersyteckie Centrum Medyczne Klinika Nefrologii Transplantologii i Chorob Wewnetrznych

Gdansk, , Poland

Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego

Lodz, , Poland

Uniwersytecki Szpital Kliniczny we Wroclawiu

Wroclaw, , Poland

LLL Medical Center Revma-Med

Kemerovo, , Russia

Orenburg State Medical University

Orenburg, , Russia

LLC Medical Sanitary Part No. 157

Saint Petersburg, , Russia

LLC German Clinic

Saint Petersburg, , Russia

Saratov Regional Clinical Hospital

Saratov, , Russia

Hosp Univ A Coruna

A Coruña, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Univ. de Basurto

Bilbao, , Spain

Hosp. Univ. Infanta Leonor

Madrid, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp. Univ. Fuenlabrada

Madrid, , Spain

Hosp. Clinico Univ. de Valencia

Valencia, , Spain

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Phramongkutklao Hospital and Medical College

Bangkok, , Thailand

Ramathibodi Hospital

Bangkok, , Thailand

Maharaj Nakorn Chiangmai Hospital

Chiang Mai, , Thailand

Songklanagarind hospital

Hat Yai, , Thailand

Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council

Cherkasy, , Ukraine

Municipal non-commercial enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, , Ukraine

City Clinical Hospital No. 2

Kryvyi Rih, , Ukraine

Medical Center 'Ok Clinic' of International Institute of Clinical Research LLC

Kyiv, , Ukraine

Kyiv Railway Clinical Hospital #2 Of Branch 'Health Center' Of The Company 'Ukrainian Railway'

Kyiv, , Ukraine

SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine

Kyiv, , Ukraine

Medical Center 'Consylium Medical'

Kyiv, , Ukraine

State Institution 'Institute of Nephrology of the National Academy of Medical Sciences of Ukraine'

Kyiv, , Ukraine

Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council

Odesa, , Ukraine

Multidisciplinary Medical Center of Odessa National Medical University

Odesa, , Ukraine

Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council

Ternopil, , Ukraine

Medical Center LTD Health Clinic Department of Cardiology and Rheumatology

Vinnytsia, , Ukraine

MNPE 'Vinnytsia Regional Clinical Hospital named after M.I. Pyrogov of Vinnytsia Regional Council'

Vinnytsia, , Ukraine

Medical Center LLC 'Modern Clinic'

Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Mexico; Poland; Russia; Spain; Taiwan; Thailand; Ukraine

References

Anders HJ, Chan TM, Sanchez-Guerrero J, Wofsy D, Bensley K, Kim L, Lo KH, Shu C, Shao J, Karyekar CS, Diamond B. Efficacy and safety of guselkumab in patients with active lupus nephritis: results from a phase 2, randomized, placebo-controlled study. Rheumatology (Oxford). 2025 May 1;64(5):2731-2740. doi: 10.1093/rheumatology/keae647.

Reference Type: DERIVED

PMID: 39673415 (View on PubMed)

Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.

Reference Type: DERIVED

PMID: 37528520 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;parentIdentifier=CR108766&amp;attachmentIdentifier=0153a0b8-08f3-4f41-a43e-b27e5d1f2be3&amp;fileName=CR108766_CSR_Synopsis.pdf&amp;versionIdentifier=

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Guselkumab in Subjects with Active Lupus Nephritis

Other Identifiers

2018-003155-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CNTO1959LUN2001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108766

Identifier Type: -

Identifier Source: org_study_id