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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04376827
Recruitment Status : Recruiting
First Posted : May 6, 2020
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE May 4, 2020
First Posted Date  ICMJE May 6, 2020
Last Update Posted Date November 25, 2020
Actual Study Start Date  ICMJE September 15, 2020
Estimated Primary Completion Date December 5, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Guselkumab in Participants With Active Lupus Nephritis
Official Title  ICMJE 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 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. 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 event (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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Lupus Nephritis
Intervention  ICMJE
  • 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  ICMJE
  • 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.
    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.
    Interventions:
    • Drug: Placebo
    • Drug: Standard-of-care treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 4, 2020)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 3, 2023
Estimated Primary Completion Date December 5, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Currently receiving prednisone equivalent dose of 1 milligram per kilogram per day (mg/kg/day) or less than or equal to (<=) 60 mg/day, whichever is lower, or less. Must be receiving prednisone equivalent of 10 mg/day or more at screening and randomization. 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 positive anti-double-stranded deoxyribonucleic acid (dsDNA) test results at screening
  • Kidney biopsy documentation of International Society of Nephrology (ISN)/Renal Pathology Society (RPS) proliferative nephritis: Class III-IV 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) cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Argentina,   Mexico,   Poland,   Russian Federation,   Spain,   Taiwan,   Thailand,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04376827
Other Study ID Numbers  ICMJE 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  ICMJE
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
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP