Study to Evaluate Efficacy and Safety of Treatment with CNTO 136 in Subjects with Active Lupus Nephritis

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2010-020968-38-BE
• Date of registration: 29/11/2010
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: Study to Evaluate Efficacy and Safety of Treatment with CNTO 136 in Subjects with Active Lupus Nephritis
• Scientific 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
• Date of first enrolment: 17/03/2011
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020968-38
• 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): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Mexico, Netherlands, Poland, Thailand, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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)


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Active Lupus Nephritis
MedDRA version: 14.1 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Product Code: CNTO136
Pharmaceutical Form: Powder for solution for injection
Current Sponsor code: CNTO 136
Other descriptive name: fully human anti-IL-6 mAb
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the percent reduction from baseline in proteinuria at Week 24. A 95% confidence interval of the mean change will be calculated based on normal
approximation. The baseline value for proteinuria will be defined as the average of the two most recent proteinuria measurements preceding the first study agent infusion.
The major secondary endpoints are proportion of subjects with a reduction from baseline in proteinuria by at least 50% at any time through Week 24; proportion of subjects with a meaningful reduction in proteinuria at any time through Week 24; and proportion of subjects with no worsening in GFR at any time through Week 24.

Secondary Objective: - Evaluate the pharmacokinetics and immunogenicity of CNTO 136 following IV
administration in subjects with active ISN/RPS Class III and IV LN
- Assess the pharmacodynamic effects of CNTO 136 IV in subjects with active
ISN/RPS Class III and IV LN

Main Objective: The primary objective is to evaluate the efficacy and safety of CNTO 136 administered
intravenously (IV) in subjects with active, International Society of Nephrology
(ISN)/Renal Pathology Society (RPS) Class III and IV lupus nephritis (LN).

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Secondary end point(s): Change from baseline in Patient’s and Physician’s Global Assessment of Disease Activity at Week 24 will be summarized by treatment group.

Secondary ID(s)

CNTO136LUN2001

Source(s) of Monetary Support

Janssen R&D Inc.