A Study of Guselkumab in Participants With Active Lupus Nephritis

Phase 2TerminatedNCT04376827

Janssen Research & Development, LLC33 enrolled

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Lupus Nephritis

Interventions

Guselkumab Dose 1DRUG

Participants will receive guselkumab Dose 1 via IV administration.

PlaceboDRUG

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.

Guselkumab Dose 2DRUG

Participants will receive guselkumab Dose 2 via SC route.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (60)

Outcomes

Primary Outcomes

Percentage of Participants Achieving at Least 50 Percent (%) Decrease From Baseline in Proteinuria at Week 24

Percentage of participants achieving at least 50% decrease in proteinuria from baseline at Week 24 was reported. Proteinuria analysis was based on urine protein creatinine ratio (UPCR) and was defined as the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease.

Time frame: Week 24

Secondary Outcomes

Percentage of Participants Who Achieved Complete Renal Response (CRR) at Week 24

Percentage of participants who achieved CRR at Week 24 were reported. CRR was defined as UPCR less than (\<) 0.5 milligrams per milligrams (mg/mg), estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 60 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2) or no confirmed decrease \>=20% from baseline and prednisone dose less than or equal to (\<=) 10 milligrams per day (mg/d). Participant was considered as achieved CRR who did not discontinue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to LN or other immunosuppressive agents, within 8 weeks prior to the outcome measure (OM) time point (Week 24) or initiation of prohibited medications at any time prior to the endpoint time point (Week 24).

Time frame: Week 24

Percentage of Participants Who Achieved CRR at Week 52

Percentage of participants who achieved CRR at Week 52 were reported. CRR was defined as UPCR less than (\<) 0.5 mg/mg, eGFR \>= 60 mL/min/1.73m\^2 or no confirmed decrease \>=20% from baseline and prednisone dose \<= 10 mg/d. Participant was considered as achieved CRR who did not discontinue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to LN or other immunosuppressive agents, within 8 weeks prior to the outcome measure time point (Week 52) or initiation of prohibited medications at any time prior to the outcome measure time point (Week 52).

Data from ClinicalTrials.gov

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

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

...and 50 more locations

Percentage of Participants Achieving a Sustained Reduction in Steroid Dose <=10 mg/d of Prednisone or Equivalent From Week 16 Through Week 24

Percentage of participants achieving a sustained reduction in steroid dose less than or equal to (\<=) 10 mg/day of prednisone or equivalent from week 16 through Week 24were reported.

Time frame: From Week 16 through Week 24

Percentage of Participants Achieving at Least 50% Decrease in Proteinuria From Baseline at Week 52

Percentage of participants achieving at least 50% decrease in proteinuria from baseline at Week 52 were reported. Proteinuria analysis was based on urine protein creatinine ratio (UPCR) and was defined as the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease.

Time frame: Week 52

Percentage of Participants With Urine Protein to Creatinine Ratio (UPCR) < 0.5 mg/mg at Week 24

Percentage of participants with UPCR \<0.5 mg/mg at Week 24 were reported.

Time frame: Week 24

Percentage of Participants With UPCR < 0.75 mg/mg at Week 24

Percentage of participants with UPCR less than 0.75 mg/mg at Week 24 were reported.

Time frame: Week 24

Percentage of Participants Who Achieved CRR Through Week 24

Percentage of participants who achieved CRR through Week 24 was reported. CRR was defined as UPCR\<0.5 mg/mg, eGFR \>= 60 mL/min/1.73m\^2 or no confirmed decrease\>=20% from baseline and prednisone dose \<= 10 mg/d. Participant was considered as achieved CRR who did not discontinue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to lupus nephritis (LN) or other immunosuppressive agents, within 8 weeks prior to the outcome measure time point (Week 24) or initiation of prohibited medications at any time prior to the outcome measure time point (Week 24).

Time frame: Up to Week 24

Percentage of Participants With Treatment Failure (TF) Through Week 52

Percentage of participants with TF through Week 52 was reported. TF was defined as time to the first occurrence of TF from baseline. Participant was considered to have treatment failure, who did not continue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to LN or other immunosuppressive agents, within 8 weeks prior to the outcome measure time point (Week 52) or initiation of prohibited medications at any time prior to the outcome measure time point (Week 52).

Time frame: Up to Week 52

Number of Participants With Adverse Events (AEs)

Number of participants with AEs were reported. An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product did not necessarily have a causal relationship with the treatment. Therefore, it could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With Serious Adverse Events (SAEs)

Number of Participants with SAEs were reported. An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product did not necessarily have a causal relationship with the treatment. Therefore, it could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With Related AEs

Number of participants with related AEs were reported. An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product did not necessarily have a causal relationship with the treatment. Therefore, it could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. Related AE was defined as the AE assessed by the investigator related to study agent.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With AEs Leading to Discontinuation of Study Intervention

Number of participants with AEs leading to discontinuation of study intervention were reported.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With Infections

Number of participants with infections as assessed by the investigator were reported.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With Serious Infections

Number of participants with serious infections as assessed by the investigator were reported.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With Infections Requiring Oral or Parenteral Antimicrobial Treatment

Number of participants with infections requiring oral or parenteral antimicrobial treatment planned to be were reported.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With AEs Temporally Associated With an Infusion

Number of participants with AEs temporally (a reaction that occurred during or within 1 hour after infusion) associated with an infusion were reported. AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product does not necessarily have a causal relationship with the treatment. Therefore, it can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Number of Participants With AEs With Injection-site Reactions

Number of participants with injection-site reactions as assessed by the investigator were reported. An injection-site reaction is any adverse reaction at a SC study intervention injection-site.

Time frame: DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96)

Change From Baseline in Clinical Laboratory Parameter: Activated Partial Thromboplastin Time

Change from baseline in clinical laboratory parameter: activated partial thromboplastin time was reported.