An Efficacy and Safety Study of CNTO 136 in Patients With Active Lupus Nephritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01273389
First received: January 7, 2011
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Lupus Nephritis
Drug: CNTO 136
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • 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) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    It is measured as the percentage in reduction of proteinuria from baseline to Week 24.


Secondary Outcome Measures:
  • Number of patients with a reduction from baseline in proteinuria by at least 50% [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    It is measured as the proportion of patients with a reduction from baseline in proteinuria by at least 50% at any time through Week 24.

  • Number of patients with a meaningful reduction in proteinuria [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    It is measured as the proportion of patients with meaningful reduction of proteinuria at any time through Week 24.

  • Number of patients with no worsening in Glomerular Filtration Rate (GFR) [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    It is measured as the proportion of patients with no worsening in GFR at any time through Week 24.

  • Patient's Global Assessment of Disease Activity [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    The Patient's Global Assessment of Disease Activity will be recorded on a visual analogue scale (VAS) (0 to 10 cm).

  • Physician's Global Assessment of Disease Activity [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    The Physician's Global Assessment of Disease Activity will be recorded on a visual analogue scale (VAS) (0 to 10 cm).


Enrollment: 25
Study Start Date: August 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CNTO 136
CNTO 136 is used in the form of final vialed product, as a single-use, sterile solution in a 2 ml glass vial. Each 1 mL of the solution contains sirukumab 100mg active drug substance, sorbitol, acetate buffer, and polysorbate 20, at a pH of 5.0, without any preservatives.
Drug: CNTO 136
Type=exact number, unit=mg/kg, number=10, form=solution for injection, route=intravenous. CNTO 136 is administered once every 4 weeks from Week 0 to Week 24.
Placebo Comparator: Placebo Drug: Placebo
Form=solution for injection, route=intravenous. Placebo is administered once every 4 weeks from Week 0 to Week 24.

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01273389

Locations
United States, Alabama
Birmingham, Alabama, United States
United States, California
Los Angeles, California, United States
United States, Illinois
Chicago, Illinois, United States
United States, New York
Lake Success, New York, United States
United States, Ohio
Columbus, Ohio, United States
United States, Pennsylvania
Duncansville, Pennsylvania, United States
United States, Tennessee
Chattanooga, Tennessee, United States
United States, Texas
Carrollton, Texas, United States
Belgium
Brussels, Belgium
Leuven, Belgium
Roeselare, Belgium
Mexico
Guadalajara, Mexico
Guadalajara, Jalisco, Mexico
Mexico, Mexico
México, Mexico
Querétaro, Mexico
Netherlands
Rotterdam, Netherlands
Poland
Gdansk, Poland
Warszawa, Poland
Wroclaw, Poland
Thailand
Bangkok, Thailand
Chiang Mai, Thailand
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01273389     History of Changes
Obsolete Identifiers: NCT01634581
Other Study ID Numbers: CR017551, CNTO136LUN2001, 2010-020968-38
Study First Received: January 7, 2011
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Lupus nephritis
CNTO 136
Sirukumab
Kidney diseases
Proteinuria
Glomerulonephritis

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 25, 2014