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

Primary Purpose

Lupus Nephritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CNTO 136
Placebo
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus nephritis, CNTO 136, Sirukumab, Kidney diseases, Proteinuria, Glomerulonephritis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CNTO 136

Placebo

Arm Description

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.

Outcomes

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)
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%
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
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)
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
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
The Physician's Global Assessment of Disease Activity will be recorded on a visual analogue scale (VAS) (0 to 10 cm).

Full Information

First Posted
January 7, 2011
Last Updated
February 25, 2016
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01273389
Brief Title
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

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
Keywords
Lupus nephritis, CNTO 136, Sirukumab, Kidney diseases, Proteinuria, Glomerulonephritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CNTO 136
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
CNTO 136
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form=solution for injection, route=intravenous. Placebo is administered once every 4 weeks from Week 0 to Week 24.
Primary Outcome Measure Information:
Title
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)
Description
It is measured as the percentage in reduction of proteinuria from baseline to Week 24.
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Number of patients with a reduction from baseline in proteinuria by at least 50%
Description
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.
Time Frame
Up to Week 24
Title
Number of patients with a meaningful reduction in proteinuria
Description
It is measured as the proportion of patients with meaningful reduction of proteinuria at any time through Week 24.
Time Frame
Up to Week 24
Title
Number of patients with no worsening in Glomerular Filtration Rate (GFR)
Description
It is measured as the proportion of patients with no worsening in GFR at any time through Week 24.
Time Frame
Up to Week 24
Title
Patient's Global Assessment of Disease Activity
Description
The Patient's Global Assessment of Disease Activity will be recorded on a visual analogue scale (VAS) (0 to 10 cm).
Time Frame
Up to Week 24
Title
Physician's Global Assessment of Disease Activity
Description
The Physician's Global Assessment of Disease Activity will be recorded on a visual analogue scale (VAS) (0 to 10 cm).
Time Frame
Up to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Lake Success
State/Province
New York
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Duncansville
State/Province
Pennsylvania
Country
United States
City
Chattanooga
State/Province
Tennessee
Country
United States
City
Carrollton
State/Province
Texas
Country
United States
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

12. IPD Sharing Statement

Citations:
PubMed Identifier
27110697
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.
Results Reference
derived

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

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