A Study of Guselkumab in Participants With Active Lupus Nephritis (ORCHID-LN)

• ClinicalTrials.gov Identifier: NCT04376827
• Recruitment Status: Terminated
• First Posted: May 6, 2020
• Results First Posted: April 16, 2024
• Last Update Posted: April 16, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: May 4, 2020
• First Posted Date: May 6, 2020
• Results First Submitted Date: February 1, 2024
• Results First Posted Date: April 16, 2024
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: September 15, 2020
• Actual Primary Completion Date: February 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2024)

Percentage of Participants Achieving at Least 50 Percent (%) Decrease From Baseline in Proteinuria at Week 24 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: May 4, 2020)

Percentage of Participants Achieving at Least 50 Percentage (%) Decrease in Proteinuria [ Time Frame: Baseline and Week 24 ]

Percentage of participants achieving at least 50% decrease in proteinuria from baseline at Week 24 will be reported.

Current Secondary Outcome Measures (submitted: March 21, 2024)

• Percentage of Participants Who Achieved Complete Renal Response (CRR) at Week 24 [ Time Frame: 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).
• Percentage of Participants Who Achieved CRR at Week 52 [ Time Frame: 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).
• Percentage of Participants Achieving a Sustained Reduction in Steroid Dose <=10 mg/d of Prednisone or Equivalent From Week 16 Through Week 24 [ Time Frame: 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.
• Percentage of Participants Achieving at Least 50% Decrease in Proteinuria From Baseline at Week 52 [ Time Frame: 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.
• Percentage of Participants With Urine Protein to Creatinine Ratio (UPCR) < 0.5 mg/mg at Week 24 [ Time Frame: Week 24 ]
  Percentage of participants with UPCR <0.5 mg/mg at Week 24 were reported.
• Percentage of Participants With UPCR < 0.75 mg/mg at Week 24 [ Time Frame: Week 24 ]
  Percentage of participants with UPCR less than 0.75 mg/mg at Week 24 were reported.
• Percentage of Participants Who Achieved CRR Through Week 24 [ Time Frame: Up to 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).
• Percentage of Participants With Treatment Failure (TF) Through Week 52 [ Time Frame: Up to 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).
• Number of Participants With Adverse Events (AEs) [ 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 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.
• Number of Participants With Serious Adverse Events (SAEs) [ 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 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.
• Number of Participants With Related AEs [ 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 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.
• Number of Participants With AEs Leading to Discontinuation of Study Intervention [ 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 were reported.
• Number of Participants With Infections [ 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 as assessed by the investigator were reported.
• Number of Participants With Serious Infections [ 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 as assessed by the investigator were reported.
• Number of Participants With Infections Requiring Oral or Parenteral Antimicrobial Treatment [ 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 planned to be were reported.
• Number of Participants With AEs Temporally Associated With an Infusion [ 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 (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.
• Number of Participants With AEs With Injection-site Reactions [ 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 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.
• Change From Baseline in Clinical Laboratory Parameter: Activated Partial Thromboplastin Time [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: activated partial thromboplastin time was reported.
• Change From Baseline in Clinical Laboratory Parameter: Basophils [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: basophils was reported.
• Change From Baseline in Clinical Laboratory Parameter: Eosinophils [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: eosinophils was reported.
• Change From Baseline in Clinical Laboratory Parameter: Erythrocytes Mean Corpuscular Hemoglobin [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: erythrocytes mean corpuscular hemoglobin was reported.
• Change From Baseline in Clinical Laboratory Parameter: Erythrocytes Mean Corpuscular Volume [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: erythrocytes mean corpuscular volume was reported.
• Change From Baseline in Clinical Laboratory Parameter: Erythrocytes [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: erythrocytes was reported.
• Change From Baseline in Clinical Laboratory Parameter: Hematocrit [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical Laboratory parameter: hematocrit was reported.
• Change From Baseline in Clinical Laboratory Parameter: Hemoglobin [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: hemoglobin was reported.
• Change From Baseline in Clinical Laboratory Parameter Leukocytes [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: leukocytes was reported.
• Change From Baseline in Clinical Laboratory Parameter: Lymphocytes [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: lymphocytes was reported.
• Change From Baseline in Clinical Laboratory Parameter: Monocytes [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: monocytes was reported.
• Change From Baseline in Clinical Laboratory Parameter: Hematology Parameter: Segmented Neutrophils [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: segmented neutrophils was reported.
• Change From Baseline in Clinical Laboratory Parameter: Platelets [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: platelets was reported.
• Change From Baseline in Clinical Laboratory Parameter: Prothrombin International Normalized Ratio [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: prothrombin international normalized ratio was reported.
• Change From Baseline in Clinical Laboratory Parameter: Prothrombin Time [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: prothrombin time was reported.
• Change From Baseline in Clinical Laboratory Parameter: Reticulocytes/Erythrocytes [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory hematology parameter:reticulocytes/erythrocytes was reported.
• Change From Baseline in Clinical Laboratory Parameter: Alanine Aminotransferase [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: alanine aminotransferase was reported.
• Change From Baseline in Clinical Laboratory Parameter: Albumin [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: albumin was reported.
• Change From Baseline in Clinical Laboratory Parameter: Alkaline Phosphatase [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: alkaline phosphatase was reported.
• Change From Baseline in Clinical Laboratory Parameter: Aspartate Aminotransferase [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: aspartate aminotransferase was reported.
• Change From Baseline in Clinical Laboratory Parameter: Bicarbonate [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: bicarbonate was reported.
• Change From Baseline in Clinical Laboratory Parameter: Bilirubin [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: bilirubin was reported.
• Change From Baseline in Clinical Laboratory Parameters: Calcium [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: calcium was reported.
• Change From Baseline in Clinical Laboratory Parameter: Chloride [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: chloride was reported.
• Change From Baseline in Clinical Laboratory Parameters: Cholesterol [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: cholesterol was reported.
• Change From Baseline in Clinical Laboratory Parameter: Creatine Kinase [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: creatine kinase was reported.
• Change From Baseline in Clinical Laboratory Parameter: Creatinine [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: creatinine was reported.
• Change From Baseline in Clinical Laboratory Parameter: Protein [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: protein was reported.
• Change From Baseline in Clinical Laboratory Parameter: Phosphate [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: phosphate was reported.
• Change From Baseline in Clinical Laboratory Parameter: Sodium [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: sodium was reported.
• Change From Baseline in Clinical Laboratory Parameters: Potassium [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: potassium was reported.
• Change From Baseline in Clinical Laboratory Parameters: Urea Nitrogen [ Time Frame: Baseline (Week 0), Week 24, and Week 52 ]
  Change from baseline in clinical laboratory parameter: urea nitrogen was reported.
• Change From Baseline in Clinical Laboratory Parameter: Glomerular Filtration Rate (GFR) From Creatinine Adjusted for Body Surface Area (BSA) [ Time Frame: Baseline (Week 0), Weeks 24 and 52 ]
  Change from baseline in clinical laboratory parameter: GFR from Creatinine Adjusted for BSA was reported.
• Change From Baseline in Clinical Laboratory Parameter: Gamma Glutamyl and Transferase Lactate Dehydrogenase [ Time Frame: Baseline (Week 0), Weeks 24 and 52 ]
  Change from baseline in clinical laboratory parameter: gamma glutamyl transferase and lactate dehydrogenase were reported.
• Change From Baseline in Clinical Laboratory Parameter: Glucose and Magnesium [ Time Frame: Baseline, Weeks 24, 52 ]
  Change from baseline in clinical laboratory parameter: glucose and magnesium were reported.
• Change From Baseline in Clinical Laboratory Parameter: Protein [ Time Frame: Baseline (Week 0), Weeks 24 and 52 ]
  Change from baseline in clinical laboratory parameter: protein was reported.
• Change From Baseline in Chemistry Parameters: Protein/Creatinine [ Time Frame: Baseline, Weeks 24 and 52 ]
  Change from baseline in chemistry parameter: protein/creatinine was reported.
• Change From Baseline in Clinical Laboratory Parameter: Urate [ Time Frame: Baseline, Weeks 24, 52 ]
  Change from baseline in clinical laboratory parameter: urate was reported.
• Change From Baseline in Clinical Laboratory Parameter: Urine Protein [ Time Frame: Baseline (Week 0), Weeks 24 and 52 ]
  Change from baseline in clinical laboratory parameter: urine protein was reported.
• Number of Participants With Maximum US National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Toxicity Grade (Grade 4) in Clinical Laboratory Parameters: Hematology and Chemistry [ 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 maximum US NCI-CTCAE toxicity grade (Grade 4) in clinical laboratory parameters: hematology and chemistry were reported. Toxicity were graded as Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
• Percentage of Participants With Abnormal Vital Signs: Systolic and Diastolic Blood Pressure [ Time Frame: Up to Week 60 ]
  Percentage of participants with abnormal vital signs: Systolic and Diastolic blood pressure were reported.
• Serum Concentration of Guselkumab [ Time Frame: Predose: Weeks 0,4,8,12,16,20,24, 36; Post-dose: Week 0 (1 hour after intravenous administration), Day 2, Week 52 and 60 ]
  Serum Concentration of guselkumab were reported.
• Number of Participants With Treatment-boosted Anti-drug Antibodies (ADA) Response [ Time Frame: From Baseline (Week 0) through Week 24 and Week 60 ]
  Treatment-boosted ADA positive participants: participants who were positive at baseline and whose titers increased 2-fold at any time after treatment. Titer values were categorized as<=1:10, 10 to 100, 100 to 1000, >1000.

Original Secondary Outcome Measures (submitted: May 4, 2020)

• Percentage of Participants Achieving Complete Renal Response (CRR) [ Time Frame: Week 24 ]
  Percentage of participants achieving complete renal response will be reported.
• Percentage of Participants Achieving a Sustained Reduction in Steroid Dose <=10 milligram (mg)/day of Prednisone or Equivalent [ Time Frame: Week 16 to Week 24 ]
  Percentage of participants achieving a sustained reduction in steroid dose less than or equal to (<=) 10 mg/day of prednisone or equivalent will be reported.
• Percentage of Participants Achieving at Least 50% Decrease in Proteinuria From Baseline at Week 52 [ Time Frame: Baseline and Week 52 ]
  Percentage of participants achieving at least 50% decrease in proteinuria from baseline at Week 52 will be reported.
• Percentage of Participants Achieving Complete Renal Response [ Time Frame: Week 52 ]
  Percentage of participants achieving CRR will be reported.
• Percentage of Participants with Urine Protein to Creatinine Ratio (UPCR) <0.5 mg/mg [ Time Frame: Week 24 ]
  Percentage of participants with UPCR <0.5 mg/mg will be reported.
• Percentage of Participants with UPCR < 0.75 mg/mg [ Time Frame: Week 24 ]
  Percentage of participants with UPCR less than (<) 0.75 milligram/milligram (mg/mg) will be reported.
• Time to achievement of Complete Renal Response [ Time Frame: Up to Week 52 ]
  Time to achievement of CRR will be reported.
• Time to Treatment Failure (TF) [ Time Frame: Up to Week 52 ]
  Time to treatment failure will be reported. Treatment failure criteria include: initiation or increased use of a glucocorticoid or other immunosuppressive agents.
• Number of Participants with Adverse Event (AE) serious adverse events (SAEs), reasonably related AEs, as a Measure of Safety and Tolerability [ Time Frame: Up to Week 60 ]
  Number of Participants with Adverse Event (AE) serious adverse events (SAEs), reasonably related AEs will be assessed. 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. A serious adverse event is any untoward medical occurrence that at any dose results in death, is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is a suspected transmission of any infectious agent via a medicinal product.
• Number of Participants with AE Leading to Discontinuation of Study Intervention [ Time Frame: Up to Week 52 ]
  Number of participants with AE leading to discontinuation of study intervention will be 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.
• Number of Participants with Infections [ Time Frame: Up to Week 60 ]
  Number of participants with infections will be reported.
• Number of Participants With Serious Infections [ Time Frame: Up to Week 60 ]
  Number of Participants with serious infections will be reported.
• Number of Participants with Infections Requiring Oral or Parenteral Antimicrobial Treatment [ Time Frame: Up to Week 60 ]
  Number of participants with infections requiring oral or parenteral antimicrobial treatment will be reported.
• Number of participants With AEs temporally associated with an infusion, and injection-site reactions [ Time Frame: Up to Week 60 ]
  Number of participants with AEs temporally associated with an infusion, and injection-site reactions will be reported. An injection-site reaction is any adverse reaction at a SC study intervention injection-site. 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.
• Change From Baseline in Laboratory Parameters [ Time Frame: Up to Week 60 ]
  Change from baseline in laboratory parameters (hematology and chemistry) will be reported.
• Number of Participants with Maximum Common Terminology Criteria for Adverse Events (CTCAE) toxicity grade Laboratory Values [ Time Frame: Up to Week 60 ]
  Number of participants with maximum CTCAE toxicity grade laboratory values will be reported. Grade refers to the severity of the AE as follows: Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2- Moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3- Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care ADL; Grade 4- Life-threatening consequences, urgent intervention indicated; Grade 5- Death related to AE.
• Systolic and Diastolic Blood Pressures Over Time [ Time Frame: Up to Week 60 ]
  Systolic and diastolic blood pressures over time will be reported.
• Serum Concentration of Guselkumab [ Time Frame: Up to Week 60 ]
  Serum Concentration of guselkumab will be reported.
• Number of Participants with Anti-Guselkumab Antibodies [ Time Frame: Up to Week 60 ]
  Number of participants with anti-drug antibodies to guselkumab will be reported.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Guselkumab in Participants With Active Lupus Nephritis
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Guselkumab in Subjects With Active Lupus Nephritis
• 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).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Lupus Nephritis

Intervention

• Drug: Guselkumab Dose 1
  Participants will receive guselkumab Dose 1 via IV administration.
  Other Name: CNTO 1959
• 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.
• Drug: Guselkumab Dose 2
  Participants will receive guselkumab Dose 2 via SC route.
  Other Name: CNTO1959
• Drug: Standard-of-care treatment
  Participants will receive standard of care treatment including MMF/MPA and glucocorticoids from Week 12 through Week 48.

Study Arms

• Experimental: 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).
  Interventions:

  • Drug: Guselkumab Dose 1
  • Drug: Guselkumab Dose 2
  • Drug: Standard-of-care treatment
• Placebo Comparator: 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.
  Interventions:

  • Drug: Placebo
  • Drug: Standard-of-care treatment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 16, 2022): 33
• Original Estimated Enrollment (submitted: May 4, 2020): 60
• Actual Study Completion Date: February 1, 2023
• Actual Primary Completion Date: February 1, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Mexico, Poland, Russian Federation, Spain, Taiwan, Thailand, Ukraine, United States

Administrative Information

• NCT Number: NCT04376827
• Other Study ID Numbers: CR108766; 2018-003155-38 ( EudraCT Number ); CNTO1959LUN2001 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: March 2024