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

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)

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.

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Mycophenolate Mofetil; Drug: Prednisolone/Prednisone; Drug: Placebo; Drug: Methylprednisolone; Drug: Laquinimod

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Teva Investigational Site 1115
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M4
      • Teva Investigational Site 1114
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Teva Investigational Site 1113
• France
  • Lille, France, 59057
    • Teva Investigational Site 3510
  • Paris, France, 75013
    • Teva Investigational Site 3509
• Russian Federation
  • Kazan, Russian Federation, 420064
    • Teva Investigational Site 5006
  • Kemerovo, Russian Federation, 650029
    • Teva Investigational Site 5007
  • Moscow, Russian Federation, 115522
    • Teva Investigational Site 5001
  • Moscow, Russian Federation, 123182
    • Teva Investigational Site 5003
  • Moscow, Russian Federation, 125284
    • Teva Investigational Site 5002
  • Yaroslavl, Russian Federation, 150062
    • Teva Investigational Site 5005
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Teva Investigational Site 3413
  • Cambridge, United Kingdom, CB2 0QQ
    • Teva Investigational Site 3409
  • Dudley, United Kingdom, DY1 2HQ
    • Teva Investigational Site 3412
  • London, United Kingdom, SE1 7EH
    • Teva Investigational Site 3410
  • Manchester, United Kingdom, M13 9WL
    • Teva Investigational Site 3411
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Teva Investigational Site 1032
  • California
    • La Jolla, California, United States, 92037-0943
      • Teva Investigational Site 1024
    • Los Angeles, California, United States, 90048
      • Teva Investigational Site 1028
    • San Leandro, California, United States, 94578
      • Teva Investigational Site 1025
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Teva Investigational Site 1031
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Teva Investigational Site 1021
  • New York
    • Lake Success, New York, United States, 11042
      • Teva Investigational Site 1022
    • Manhasset, New York, United States, 11030
      • Teva Investigational Site 1018
    • New York, New York, United States, 10016
      • Teva Investigational Site 1019
    • New York, New York, United States, 10032
      • Teva Investigational Site 1017
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Teva Investigational Site 1020
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Teva Investigational Site 1016
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Teva Investigational Site 1030
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Teva Investigational Site 1026

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Mycophenolate Mofetil (MMF) will be administered per dose and schedule specified in the arm description.; Drug: Prednisolone/Prednisone; Prednisolone/Prednisone will be administered per dose and schedule specified in the arm description.; Drug: Placebo; Placebo matching to laquinimod will be administered per schedule specified in the arm description.; Drug: Methylprednisolone; Methylprednisolone (MP) will be administered per dose and schedule specified in the arm description.
Experimental: Laquinimod 0.5 mg; 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: Mycophenolate Mofetil; Mycophenolate Mofetil (MMF) will be administered per dose and schedule specified in the arm description.; Drug: Prednisolone/Prednisone; Prednisolone/Prednisone will be administered per dose and schedule specified in the arm description.; Drug: Placebo; Placebo matching to laquinimod will be administered per schedule specified in the arm description.; Drug: Methylprednisolone; Methylprednisolone (MP) will be administered per dose and schedule specified in the arm description.; Drug: Laquinimod; Laquinimod will be administered per dose and schedule specified in the arm description.
Experimental: Laquinimod 1 mg; 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: Mycophenolate Mofetil; Mycophenolate Mofetil (MMF) will be administered per dose and schedule specified in the arm description.; Drug: Prednisolone/Prednisone; Prednisolone/Prednisone will be administered per dose and schedule specified in the arm description.; Drug: Methylprednisolone; Methylprednisolone (MP) will be administered per dose and schedule specified in the arm description.; Drug: Laquinimod; Laquinimod will be administered per dose and schedule specified in the arm description.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2010
• Primary Completion (Actual): October 24, 2012
• Study Completion (Actual): October 24, 2012

Study Registration Dates

• First Submitted: March 4, 2010
• First Submitted That Met QC Criteria: March 9, 2010
• First Posted (Estimate): March 11, 2010

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus (SLE); Lupus Nephritis; Laquinimod
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone; Mycophenolic Acid
• Other Study ID Numbers: LN-LAQ-201; 2010-018329-20 (EudraCT Number)