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

Phase 2
Completed
Conditions
Lupus Nephritis
Interventions
Registration Number
NCT01085097
Lead Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
46
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants 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.
Laquinimod 0.5 mgPlaceboParticipants 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.
Laquinimod 0.5 mgPrednisolone/PrednisoneParticipants 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.
Laquinimod 1 mgPrednisolone/PrednisoneParticipants 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.
PlaceboPrednisolone/PrednisoneParticipants 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.
PlaceboMycophenolate MofetilParticipants 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.
Laquinimod 0.5 mgLaquinimodParticipants 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.
Laquinimod 0.5 mgMycophenolate MofetilParticipants 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.
Laquinimod 1 mgLaquinimodParticipants 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.
Laquinimod 1 mgMycophenolate MofetilParticipants 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.
PlaceboMethylprednisoloneParticipants 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.
Laquinimod 0.5 mgMethylprednisoloneParticipants 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.
Laquinimod 1 mgMethylprednisoloneParticipants 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.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Adverse Events (AEs)Baseline up to Week 28

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'.

Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24Baseline, Week 24

Estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (30)

Teva Investigational Site 1022

🇺🇸

Lake Success, New York, United States

Teva Investigational Site 3412

🇬🇧

Dudley, United Kingdom

Teva Investigational Site 1114

🇨🇦

Winnipeg, Manitoba, Canada

Teva Investigational Site 1032

🇺🇸

Phoenix, Arizona, United States

Teva Investigational Site 1028

🇺🇸

Los Angeles, California, United States

Teva Investigational Site 1025

🇺🇸

San Leandro, California, United States

Teva Investigational Site 1031

🇺🇸

Baltimore, Maryland, United States

Teva Investigational Site 1113

🇨🇦

Toronto, Ontario, Canada

Teva Investigational Site 1024

🇺🇸

La Jolla, California, United States

Teva Investigational Site 1021

🇺🇸

Rochester, Minnesota, United States

Teva Investigational Site 1018

🇺🇸

Manhasset, New York, United States

Teva Investigational Site 1019

🇺🇸

New York, New York, United States

Teva Investigational Site 1017

🇺🇸

New York, New York, United States

Teva Investigational Site 1020

🇺🇸

Charlotte, North Carolina, United States

Teva Investigational Site 1016

🇺🇸

Columbus, Ohio, United States

Teva Investigational Site 1030

🇺🇸

Charleston, South Carolina, United States

Teva Investigational Site 1026

🇺🇸

Chattanooga, Tennessee, United States

Teva Investigational Site 1115

🇨🇦

Edmonton, Alberta, Canada

Teva Investigational Site 3510

🇫🇷

Lille, France

Teva Investigational Site 5006

🇷🇺

Kazan, Russian Federation

Teva Investigational Site 3509

🇫🇷

Paris, France

Teva Investigational Site 5007

🇷🇺

Kemerovo, Russian Federation

Teva Investigational Site 5001

🇷🇺

Moscow, Russian Federation

Teva Investigational Site 5003

🇷🇺

Moscow, Russian Federation

Teva Investigational Site 3409

🇬🇧

Cambridge, United Kingdom

Teva Investigational Site 3413

🇬🇧

Birmingham, United Kingdom

Teva Investigational Site 5005

🇷🇺

Yaroslavl, Russian Federation

Teva Investigational Site 5002

🇷🇺

Moscow, Russian Federation

Teva Investigational Site 3410

🇬🇧

London, United Kingdom

Teva Investigational Site 3411

🇬🇧

Manchester, United Kingdom

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