Clinical trial NCT04376827: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lupus Nephritis
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-05-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Percentage of Participants Achieving at Least 50 Percent (%) Decrease From Baseline in Proteinuria at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Who Achieved Complete Renal Response (CRR) at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Achieved CRR at Week 52
timeFrame: Week 52
measure: Percentage of Participants Achieving a Sustained Reduction in Steroid Dose <=10 mg/d of Prednisone or Equivalent From Week 16 Through Week 24
timeFrame: From Week 16 through Week 24
measure: Percentage of Participants Achieving at Least 50% Decrease in Proteinuria From Baseline at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Urine Protein to Creatinine Ratio (UPCR) < 0.5 mg/mg at Week 24
timeFrame: Week 24
measure: Percentage of Participants With UPCR < 0.75 mg/mg at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Achieved CRR Through Week 24
timeFrame: Up to Week 24
measure: Percentage of Participants With Treatment Failure (TF) Through Week 52
timeFrame: Up to Week 52
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Number of Participants With Related AEs
timeFrame: 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)
measure: Number of Participants With AEs Leading to Discontinuation of Study Intervention
timeFrame: 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)
measure: Number of Participants With Infections
timeFrame: 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)
measure: Number of Participants With Serious Infections
timeFrame: 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)
measure: Number of Participants With Infections Requiring Oral or Parenteral Antimicrobial Treatment
timeFrame: 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)
measure: Number of Participants With AEs Temporally Associated With an Infusion
timeFrame: 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)
measure: Number of Participants With AEs With Injection-site Reactions
timeFrame: 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)
measure: Change From Baseline in Clinical Laboratory Parameter: Activated Partial Thromboplastin Time
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Basophils
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Eosinophils
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Erythrocytes
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Hematocrit
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Hemoglobin
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter Leukocytes
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Lymphocytes
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Monocytes
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Hematology Parameter: Segmented Neutrophils
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Platelets
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Prothrombin International Normalized Ratio
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Prothrombin Time
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Reticulocytes/Erythrocytes
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Alanine Aminotransferase
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Albumin
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Alkaline Phosphatase
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Aspartate Aminotransferase
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Bicarbonate
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Bilirubin
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameters: Calcium
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Chloride
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameters: Cholesterol
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Creatine Kinase
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Creatinine
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Protein
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Phosphate
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Sodium
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameters: Potassium
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameters: Urea Nitrogen
timeFrame: Baseline (Week 0), Week 24, and Week 52
measure: Change From Baseline in Clinical Laboratory Parameter: Glomerular Filtration Rate (GFR) From Creatinine Adjusted for Body Surface Area (BSA)
timeFrame: Baseline (Week 0), Weeks 24 and 52
measure: Change From Baseline in Clinical Laboratory Parameter: Gamma Glutamyl and Transferase Lactate Dehydrogenase
timeFrame: Baseline (Week 0), Weeks 24 and 52
measure: Change From Baseline in Clinical Laboratory Parameter: Glucose and Magnesium
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Clinical Laboratory Parameter: Protein
timeFrame: Baseline (Week 0), Weeks 24 and 52
measure: Change From Baseline in Chemistry Parameters: Protein/Creatinine
timeFrame: Baseline, Weeks 24 and 52
measure: Change From Baseline in Clinical Laboratory Parameter: Urate
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Clinical Laboratory Parameter: Urine Protein
timeFrame: Baseline (Week 0), Weeks 24 and 52
measure: 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
timeFrame: 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)
measure: Percentage of Participants With Abnormal Vital Signs: Systolic and Diastolic Blood Pressure
timeFrame: Up to Week 60
measure: Serum Concentration of Guselkumab
timeFrame: 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
measure: Number of Participants With Treatment-boosted Anti-drug Antibodies (ADA) Response
timeFrame: From Baseline (Week 0) through Week 24 and Week 60
Other outcomes:
Locations:
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Brooklyn
country: United States
facility: NYU Langone Ambulatory Care Brooklyn Heights
state: New York
city: Manhasset
country: United States
facility: The Feinstein Institute for Medical Research
state: New York
city: El Paso
country: United States
facility: Med Research, Inc.
state: Texas
city: Buenos Aires
country: Argentina
facility: Centro Médico Reumatológico (OMI)
city: Caba
country: Argentina
facility: Hospital Ramos Mejia
city: Caba
country: Argentina
facility: ARCIS Salud SRL Aprillus asistencia e investigacion
city: Cordoba
country: Argentina
facility: Instituto Medico Strusberg SA
city: Córdoba
country: Argentina
facility: Clinica Privada Velez Sarsfield
city: Mendoza
country: Argentina
facility: Instituto de Reumatologia - Ir Medical Center S.A.
city: Rosario
country: Argentina
facility: Instituto Médico de la Fundación de Estudios Clínicos (ECLIN)
city: San Miguel De Tucuman
country: Argentina
facility: Centro de Investigaciones Medicas Tucuman
city: Ciudad de Mexico
country: Mexico
facility: Centro de Investigacion y Tratamiento Reumatologico S C
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
city: Merida
country: Mexico
facility: Unidad Reumatologica las Americas S.C.P.
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
city: Mexico
country: Mexico
facility: Consultorio de Reumatologia
city: San Luis Potosi
country: Mexico
facility: Unidad de Investigaciones Reumatologicas A.C
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Medyczne Klinika Nefrologii Transplantologii i Chorob Wewnetrznych
city: Lodz
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny we Wroclawiu
city: Kemerovo
country: Russian Federation
facility: LLL Medical Center Revma-Med
city: Orenburg
country: Russian Federation
facility: Orenburg State Medical University
city: Saint-Petersburg
country: Russian Federation
facility: LLC Medical Sanitary Part No. 157
city: Saratov
country: Russian Federation
facility: Saratov Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: LLC German Clinic
city: A Coruna
country: Spain
facility: Hosp Univ A Coruna
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Bilbao
country: Spain
facility: Hosp. Univ. de Basurto
city: Madrid
country: Spain
facility: Hosp. Univ. Infanta Leonor
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. Fuenlabrada
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital and Medical College
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiangmai Hospital
city: Hat Yai
country: Thailand
facility: Songklanagarind hospital
city: Cherkasy
country: Ukraine
facility: Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
city: Kharkiv
country: Ukraine
facility: Municipal non-commercial enterprise of Kharkiv Regional Council Regional Clinical Hospital
city: Kryvyi Rih
country: Ukraine
facility: City Clinical Hospital No. 2
city: Kyiv
country: Ukraine
facility: Medical Center 'Ok Clinic' of International Institute of Clinical Research LLC
city: Kyiv
country: Ukraine
facility: Kyiv Railway Clinical Hospital #2 Of Branch 'Health Center' Of The Company 'Ukrainian Railway'
city: Kyiv
country: Ukraine
facility: SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
city: Kyiv
country: Ukraine
facility: Medical Center 'Consylium Medical'
city: Kyiv
country: Ukraine
facility: State Institution 'Institute of Nephrology of the National Academy of Medical Sciences of Ukraine'
city: Odessa
country: Ukraine
facility: Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council
city: Odessa
country: Ukraine
facility: Multidisciplinary Medical Center of Odessa National Medical University
city: Ternopil
country: Ukraine
facility: Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
city: Vinnytsia
country: Ukraine
facility: MNPE 'Vinnytsia Regional Clinical Hospital named after M.I. Pyrogov of Vinnytsia Regional Council'
city: Vinnytsya
country: Ukraine
facility: Medical Center LTD Health Clinic Department of Cardiology and Rheumatology
city: Zaporizhzhya
country: Ukraine
facility: Medical Center LLC 'Modern Clinic'
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: