Lupus Nephritis
Conditions
Keywords
Systemic Lupus Erythematosus (SLE), Lupus Nephritis, Laquinimod
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.
Interventions
DRUGLaquinimod
Laquinimod will be administered per dose and schedule specified in the arm description.
DRUGMycophenolate Mofetil
Mycophenolate Mofetil (MMF) will be administered per dose and schedule specified in the arm description.
DRUGPrednisolone/Prednisone
Prednisolone/Prednisone will be administered per dose and schedule specified in the arm description.
DRUGPlacebo
Placebo matching to laquinimod will be administered per schedule specified in the arm description.
DRUGMethylprednisolone
Methylprednisolone (MP) will be administered per dose and schedule specified in the arm description.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 24 | Baseline, Week 24 | Estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. |
Countries
Canada, France, Russia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 2 capsules of placebo matched 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 was 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. | 15 |
| Laquinimod 0.5 mg Participants received 1 capsule of laquinimod 0.5 mg and 1 capsule of placebo matched 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 was 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. | 16 |
| Laquinimod 1 mg Participants received 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 was 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. | 15 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
| Overall Study | Treatment failure | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Laquinimod 0.5 mg | Laquinimod 1 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 33.4 years STANDARD_DEVIATION 10.9 | 35.3 years STANDARD_DEVIATION 11.5 | 32.7 years STANDARD_DEVIATION 9.7 | 33.8 years STANDARD_DEVIATION 10.6 |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 1 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 11 Participants | 9 Participants | 27 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 13 Participants | 34 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 2 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 16 | 1 / 15 |
| other Total, other adverse events | 14 / 15 | 13 / 16 | 15 / 15 |
| serious Total, serious adverse events | 4 / 15 | 4 / 16 | 4 / 15 |
Outcome results
Primary
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'.
Time frame: Baseline up to Week 28
Population: Safety analysis set included all randomly assigned participants who received at least 1 dose of study drug. In this set, participants were assigned to the treatment actually received, regardless of the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | 14 participants |
| Laquinimod 0.5 mg | Number of Participants With Adverse Events (AEs) | 15 participants |
| Laquinimod 1 mg | Number of Participants With Adverse Events (AEs) | 15 participants |
Primary
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.
Time frame: Baseline, Week 24
Population: Modified intent-to-treat (mITT) analysis set included all randomized participants, excluding observations after treatment failure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24 | 12.1 percent change | Standard Deviation 20.17 |
| Laquinimod 0.5 mg | Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24 | 18.0 percent change | Standard Deviation 30.65 |
| Laquinimod 1 mg | Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24 | 24.3 percent change | Standard Deviation 28.84 |