A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV Lupus Nephritis (LUNAR)

• Register: EUCTR
• Last refreshed on: 16 August 2016
• Main ID: EUCTR2016-003201-34-Outside-EU/EEA
• Date of registration: 07/08/2016
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche AG
• Public title: A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV Lupus Nephritis (LUNAR)
• Scientific title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis
• Target sample size: 140
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003201-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Canada, Mexico, United States

Contacts

• Name: Roche Trial Information Hotline
• Affiliation: F. Hoffmann-La Roche AG

• Name: Roche Trial Information Hotline
• Affiliation: F. Hoffmann-La Roche AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria.
• Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (LN), with either active or active/chronic disease.
• Proteinuria.
• 16-75 years of age.
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 141
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE.
• Unstable subjects with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions.
• Lack of peripheral venous access.
• Pregnancy or lactation.
• History of severe allergic or anaphylactic reactions to monoclonal antibodies.
• Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude subject participation.
• Concomitant chronic conditions, excluding SLE (eg, asthma, Crohn's disease) that require oral or systemic corticosteroid use in the 52 weeks prior to screening.
• History of renal transplant.
• Known human immunodeficiency virus (HIV) infection.
• Known active infection of any kind (but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives within 4 weeks of randomization or oral anti-infectives within 2 weeks of randomization.
• History of deep space infection within 1 year of screening.
• History of serious recurrent or chronic infection.
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinomas of the skin that have been treated or excised and have resolved).
• Currently active alcohol or drug abuse or history of alcohol or drug abuse within 52 weeks prior to screening.
• Major surgery requiring hospitalization within 4 weeks of screening (excluding diagnostic surgery).
• Treatment with cyclophosphamide or calcineurin inhibitors within the 90 days prior to screening.
• Use of mycophenolate mofetil (MMF) at a dose of > 2 grams daily for longer than the 90 days prior to screening.
• Intolerance or history of allergic reaction to MMF.
• Intolerance or history of allergic reaction to both angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers.
• Use of oral predisone (or corticosteroid equivalent) at a dose of > 20 mg/day but <60 mg/day for longer than the 28 days prior to screening.
• Previous treatment with CAMPATH-1H (alemtuzumab).
• Previous treatment with a B-cell targeted therapy.
• Treatment with any investigational agent (including biologic agents approved for other indications) within 28 days of the start of the screening period or 5 half-lives of the investigational drug (whichever is longer).
• Receipt of a live vaccine within the 28 days prior to screening.
• Intolerance or contraindication to oral or IV corticosteroids.
• Current therapy with a nonsteroidal anti-inflammatory agent.
• Positive hepatitis B sAg or hepatitis C serology.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ISN/RPS 2003 Class III or IV Lupus Nephritis
MedDRA version: 19.0 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: Rituxan
Pharmaceutical Form: Injection
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Intravenous use

Trade Name: CellCept
Pharmaceutical Form: Tablet
INN or Proposed INN: MYCOPHENOLATE MOFETIL
Other descriptive name: MYCOPHENOLATE MOFETIL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study are to evaluate the efficacy of rituximab in combination with MMF compared with placebo in combination with MMF in subjects diagnosed with ISN/RPS 2003 Class III or IV LN to:
• Induce an early complete renal response and maintain it to Week 52
• Induce a complete renal response at Week 52
• Reduce nephrotic-range proteinuria
• Decrease overall systemic lupus erythematosus (SLE) disease activity
• Induce an early partial renal response and maintain it
• Improve measures of quality of life
• Reduce autoantibody levels and increase complement levels

Main Objective: The primary objective of this study is to evaluate the efficacy and safety of rituximab in combination with mycophenolate mofetil (MMF) compared with placebo in combination with MMF in subjects diagnosed with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (LN), as assessed by improvements in renal function, urinary sediment, and proteinuria.

Timepoint(s) of evaluation of this end point: Week 52

Primary end point(s): • Percentage of Participants Who Achieved a Renal Response at Week 52

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to Week 52

Secondary end point(s): • Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52
• Time to First Complete Renal Response (CRR)
• Percentage of Participants with a Baseline Urine Protein to Creatinine Ratio of > 3.0 Who Achieved a Ratio of < 1.0 at Week 52
• Percentage of Participants Who Achieved a Complete Renal Response (CRR) at Week 24 and Maintained it to Week 52
• Time-Adjusted Area Under the Curve Minus Baseline (AUCMB) of the British Isles Lupus Assessment Group (BILAG) index global score over 52 weeks
• Change From Baseline to Week 52 in the Systemic Lupus Erythematosus (SLE) Expanded Health Survey Physical Function Score

Secondary ID(s)

GA01378

NCT00282347

U2970g

Source(s) of Monetary Support

F. Hoffmann-La Roche AG