A Study of Laquinimod in Participants With Systemic Lupus Erythematosus (SLE) Active Lupus Nephritis

Study Overview
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Brief Summary
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The study aims to evaluate the safety and clinical effect of daily oral treatment with laquinimod capsules in active lupus nephritis participants. This study will assess Laquinimod doses of 0.5 milligrams (mg)/day and 1 mg/day in combination with standard of care treatment (mycophenolate mofetil [MMF] and corticosteroids). Laquinimod is a novel immunomodulating drug which is currently in advanced stages of development by Teva Pharmaceuticals Ltd. for Multiple Sclerosis.

Official Title
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A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability and Clinical Effect of Laquinimod in Active Lupus Nephritis Patients, in Combination With Standard of Care (Mycophenolate Mofetil and Steroids)

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Laquinimod
* Drug: Mycophenolate Mofetil
* Drug: Prednisolone/Prednisone
* Drug: Placebo
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed with SLE Kidney biopsy within 12 months prior to baseline with a histological diagnosis of proliferative or membranous Lupus Nephritis (LN) Clinically active Lupus Nephritis as evident by urine protein-to-creatinine ratio (UPCR) of 1 or higher, for LN classes III, IV, or class V in combination with classes III or IV, or a UPCR of 2 or higher for LN class V, at screening or any time between screening and baseline. Exclusion Criteria: Participants with severe renal impairment or dialysis Participants with a clinically significant or unstable medical or surgical condition Women who are pregnant or nursing or who intend to be during the study period Women of child-bearing potential who do not practice an acceptable method of birth control NOTE: Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive 2 capsules of placebo matching to laquinimod orally once daily (QD) for 24 weeks, MMF 500 mg tablet orally twice daily (BID) for the first week then 1 gram (g) BID from Week 2 to Week 28, and MP 500 mg/day intravenously (IV) from Days 1 through 3, followed by oral prednisolone/prednisone (initial dose 40 mg/day which is tapered to 10 mg/day or less by the end of Week 20, on a fixed steroid-tapering regimen) from Day 4 through Week 28. | Drug: Mycophenolate Mofetil<br>* Mycophenolate Mofetil (MMF) will be administered per dose and schedule specified in the arm description.<br>Drug: Prednisolone/Prednisone<br>* Prednisolone/Prednisone will be administered per dose and schedule specified in the arm description.<br>Drug: Placebo<br>* Placebo matching to laquinimod will be administered per schedule specified in the arm description.<br>Drug: Methylprednisolone<br>* Methylprednisolone (MP) will be administered per dose and schedule specified in the arm description.<br>|
| Experimental: Laquinimod 0.5 mg<br>Participants will receive 1 capsule of laquinimod 0.5 mg and 1 capsule of placebo matching to laquinimod orally QD for 24 weeks, MMF 500 mg tablet orally BID for the first week then 1 g BID from Week 2 to Week 28, and MP 500 mg/day IV from Days 1 through 3, followed by oral prednisolone/prednisone (initial dose 40 mg/day which is tapered to 10 mg/day or less by the end of Week 20, on a fixed steroid-tapering regimen) from Day 4 through Week 28. | Drug: Laquinimod<br>* Laquinimod will be administered per dose and schedule specified in the arm description.<br>Drug: Mycophenolate Mofetil<br>* Mycophenolate Mofetil (MMF) will be administered per dose and schedule specified in the arm description.<br>Drug: Prednisolone/Prednisone<br>* Prednisolone/Prednisone will be administered per dose and schedule specified in the arm description.<br>Drug: Placebo<br>* Placebo matching to laquinimod will be administered per schedule specified in the arm description.<br>Drug: Methylprednisolone<br>* Methylprednisolone (MP) will be administered per dose and schedule specified in the arm description.<br>|
| Experimental: Laquinimod 1 mg<br>Participants will receive 2 capsules of laquinimod 0.5 mg orally QD for 24 weeks, MMF 500 mg tablet orally BID for the first week then 1 g BID from Week 2 to Week 28, and MP 500 mg/day IV from Days 1 through 3, followed by oral prednisolone/prednisone (initial dose 40 mg/day which is tapered to 10 mg/day or less by the end of Week 20, on a fixed steroid-tapering regimen) from Day 4 through Week 28. | Drug: Laquinimod<br>* Laquinimod will be administered per dose and schedule specified in the arm description.<br>Drug: Mycophenolate Mofetil<br>* Mycophenolate Mofetil (MMF) will be administered per dose and schedule specified in the arm description.<br>Drug: Prednisolone/Prednisone<br>* Prednisolone/Prednisone will be administered per dose and schedule specified in the arm description.<br>Drug: Methylprednisolone<br>* Methylprednisolone (MP) will be administered per dose and schedule specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. | Baseline up to Week 28 | 
| Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24 | Estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. | Baseline, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus (SLE), Lupus Nephritis, Laquinimod