A Study of Guselkumab in Participants With Active Lupus Nephritis (ORCHID-LN)
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| ClinicalTrials.gov Identifier: NCT04376827 |
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Recruitment Status :
Recruiting
First Posted : May 6, 2020
Last Update Posted : January 3, 2022
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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Brief Summary:
The purpose of this study is to evaluate the efficacy of guselkumab in participants with active lupus nephritis (LN).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lupus Nephritis | Drug: Guselkumab Dose 1 Drug: Placebo Drug: Guselkumab Dose 2 Drug: Standard-of-care treatment | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Guselkumab in Subjects With Active Lupus Nephritis |
| Actual Study Start Date : | September 15, 2020 |
| Estimated Primary Completion Date : | December 5, 2022 |
| Estimated Study Completion Date : | October 16, 2025 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Guselkumab
| Arm | Intervention/treatment |
|---|---|
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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 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).
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Drug: Guselkumab Dose 1
Participants will receive guselkumab Dose 1 via IV administration.
Other Name: CNTO 1959 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. |
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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 complete the assessments at Week 52 and have achieved CRR may have the option to participate in the LTE of the study.
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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: Standard-of-care treatment Participants will receive standard of care treatment including MMF/MPA and glucocorticoids from Week 12 through Week 48. |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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 160 ]Number of participants with anti-drug antibodies to guselkumab will be reported.
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04376827
Contacts
| Contact: Study Contact | 844-434-4210 | JNJ.CT@sylogent.com |
Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Additional Information:
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT04376827 |
| Other Study ID Numbers: |
CR108766 2018-003155-38 ( EudraCT Number ) CNTO1959LUN2001 ( Other Identifier: Janssen Research & Development, LLC ) |
| First Posted: | May 6, 2020 Key Record Dates |
| Last Update Posted: | January 3, 2022 |
| Last Verified: | December 2021 |
| Individual Participant Data (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 |
| 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 |
Additional relevant MeSH terms:
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Nephritis Lupus Nephritis Kidney Diseases Urologic Diseases Glomerulonephritis Lupus Erythematosus, Systemic |
Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |