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

NCT ID: NCT01273389

Last Updated: 2016-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2013-09-30

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.

Conditions

Lupus Nephritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

CNTO 136

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Form=solution for injection, route=intravenous. Placebo is administered once every 4 weeks from Week 0 to Week 24.

Interventions

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.

Intervention Type: DRUG

Placebo

Form=solution for injection, route=intravenous. Placebo is administered once every 4 weeks from Week 0 to Week 24.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Los Angeles, California, United States

Chicago, Illinois, United States

Lake Success, New York, United States

Columbus, Ohio, United States

Duncansville, Pennsylvania, United States

Chattanooga, Tennessee, United States

Carrollton, Texas, United States

Brussels, , Belgium

Leuven, , Belgium

Roeselare, , Belgium

Guadalajara, , Mexico

Guadalajara, Jalisco, , Mexico

México, , Mexico

Querétaro, , Mexico

Rotterdam, , Netherlands

Gdansk, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Bangkok, , Thailand

Chiang Mai, , Thailand

Countries

United States; Belgium; Mexico; Netherlands; Poland; Thailand

References

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.

Reference Type: DERIVED

PMID: 27110697 (View on PubMed)

Other Identifiers

CNTO136LUN2001

Identifier Type: OTHER

Identifier Source: secondary_id

2010-020968-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR017551

Identifier Type: -

Identifier Source: org_study_id

NCT01634581

Identifier Type: -

Identifier Source: nct_alias