Clinical trial NCT01273389: An Efficacy and Safety Study of CNTO 136 in Patients With Active Lupus Nephritis
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study to Evaluate Efficacy and Safety of Treatment With CNTO 136 Administered Intravenously in Subjects With Active Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Nephritis
Keywords: Lupus nephritis
CNTO 136
Sirukumab
Kidney diseases
Proteinuria
Glomerulonephritis
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-01-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of CNTO 136 administered intravenously in patients with active, International Society of Nephrology/Renal Pathology Society Class III and IV Lupus Nephritis (LN).

Detailed description: This is a multicenter (study conducted at multiple sites), randomized (the study medication is assigned by chance), double-blind (neither investigator nor the patient knows the treatment that the patient receives), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), parallel group (each group of patients will be treated at the same time) study of CNTO 136 in patients with active LN. The study consists of 3 phases, ie, the screening phase (approximately 8 weeks prior randomization), treatment phase (24 weeks), and the follow up phase (through week 40). An 8 week run-in period will be used to establish the stability of baseline renal parameters prior to randomization and the first study medication. The eligible patients will be randomly assigned in a 5:1 ratio to receive 1 of 2 treatment groups in the treatment phase: Group 1: CNTO 136 10 mg/kg intravenous (IV), at Weeks 0, 4, 8, 12, 16, 20, 24; and Group 2: Placebo infusion, IV, at Weeks 0, 4, 8, 12, 16, 20, 24. Patients' medication regimen for LN may be adjusted from the Week 24 visit and afterwards. Safety evaluations for adverse events, infections, clinical laboratory tests, electrocardiogram, vital signs, physical examination and skin evaluations will be performed throughout the study. The follow up phase or the end of study will be the Week 40 visit for the last patient randomized, or, in the event that the last patient randomized withdraws from the study early, the end of study is defined as the date of the last visit of the last patient participating in the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Systemic lupus erythematosus (SLE), and biopsy-proven International Society of Nephrology/Renal Pathology Society Class III or IV lupus glomerulonephritis within approximately 14 months prior to randomization
* Persistently active nephritis defined as, proteinuria greater than 0.5g/day as determined by measurement of total urine protein less than 0.5 g/24- hours or a urine Protein/Creatinine (P/C) ratio greater than 0.5 (mg/mg) in a timed collection of 12 or more hours, for 2 months or more prior to the first administration of study medication and observed during at least 2 visits conducted 1 week apart during the screening period
* Active Class III or Class IV lupus nephritis determined by recent biopsy within approximately 6 months prior to screening or at least 1 of the following 3 criteria: hematuria (blood in urine), anti-DNA positivity, or low C3 or C4 complement levels
* Stable immunosuppression for at least 9 weeks prior to the first administration of study medication consisting of MMF 1-3 g/day (or equivalent dose of MPA) with/without corticosteroids up to prednisone equivalent of 20 mg/day, or azathioprine 1-3 mg/kg/day with/without corticosteroids up to prednisone equivalent of 20 mg/day
* Stable dose of angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) for at least 9 weeks prior to the first administration of study medication
* If using oral corticosteroids, must be on a stable dose equivalent to 20 mg/day or less of prednisone for at least 9 weeks prior to the first administration of study medication

Exclusion Criteria:

* Cyclophosphamide use within 3 months of randomization
* B-cell depletion therapy within 6 months of screening, or evidence of persistent B-cell depletion at the time of screening
* Greater than 50 percent glomerular sclerosis on renal biopsy
* Serum creatinine \> 2.5 mg/dL (SI: \> 177 µmol/L)
* White blood cell count \< 3.5 x 10\^3 cells/µL (SI: \< 3.5 x 10\^9 cells/L) or neutrophils \< 1.96 x 10\^3 cells/µL (SI: \< 1.96 x 10\^9 cells/L)
* Platelets \< 140 x 103 cells/ µL (SI: \< 140 x 10\^9 cells/L)

Primary outcomes:
measure: Number of patients with reduction in proteinuria (measurement of total urine protein greater than 0.5 g/24-hours, or a urine protein to creatinine ratio greater than 0.5 mg/mg)
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Number of patients with a reduction from baseline in proteinuria by at least 50%
timeFrame: Up to Week 24
measure: Number of patients with a meaningful reduction in proteinuria
timeFrame: Up to Week 24
measure: Number of patients with no worsening in Glomerular Filtration Rate (GFR)
timeFrame: Up to Week 24
measure: Patient's Global Assessment of Disease Activity
timeFrame: Up to Week 24
measure: Physician's Global Assessment of Disease Activity
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Lake Success
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Chattanooga
country: United States
state: Tennessee
city: Carrollton
country: United States
state: Texas
city: Brussels
country: Belgium
city: Leuven
country: Belgium
city: Roeselare
country: Belgium
city: Guadalajara, Jalisco
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico
country: Mexico
city: México
country: Mexico
city: Querétaro
country: Mexico
city: Rotterdam
country: Netherlands
city: Gdansk
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Rovin BH, van Vollenhoven RF, Aranow C, Wagner C, Gordon R, Zhuang Y, Belkowski S, Hsu B. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Treatment With Sirukumab (CNTO 136) in Patients With Active Lupus Nephritis. Arthritis Rheumatol. 2016 Sep;68(9):2174-83. doi: 10.1002/art.39722.