A Study of the Safety and Pharmacokinetics of CNTO 136 in Patients With Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus

A Phase 1, Double-blind, Placebo-controlled, Multiple Intravenous, Ascending-Dose Study of CNTO 136 to Evaluate Safety and Pharmacokinetics in Subjects With Cutaneous Lupus Erythematosus and to Evaluate Safety and Pharmacokinetics in a Cohort of Subjects With Systemic Lupus Erythematosus

The main purpose of this study was to evaluate the safety and pharmacokinetics (PK, the action of a drug in the body over a period of time) of multiple intravenous (IV) administrations of CNTO 136 in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). The secondary goal of this study was to assess the pharmacodynamics (biochemical and physiological effects of a drug and the mechanisms of action), immune response, and clinical response.

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous
• Intervention / Treatment: Drug: 1 mg/kg CNTO 136; Drug: 4 mg/kg CNTO 136; Drug: 10 mg/kg CNTO 136; Drug: Placebo

Detailed Description

In Part A of this study, patients with CLE were randomly assigned (like flipping a coin) to receive multiple IV doses of CNTO 136, a human anti-IL 6 monoclonal antibody (an immune protein that binds to interleukin 6) or placebo (a substance that appears identical to the treatment and has no active ingredients). Patients and study personnel did not know the identity of the administered treatments (double-blind study). Increasing doses were given, based on safety data collected during the initial weeks of treatment. In Part B, which was also double-blind, patients with SLE were randomly assigned to receive multiple IV doses of the highest well-tolerated dose, as determined in Part A, of CNTO 136, or placebo.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of cutaneous lupus erythematosus (CLE, including subacute cutaneous lupus erythematosus, discoid lupus erythematosus, or lupus erythematosus tumidus) or systemic lupus erythematosus (SLE)

  • Had a body weight less than or equal to 100 kg
  • Patients in Part A who were taking systemic medications for CLE had to be on a stable dose for 4 weeks before the first study agent infusion
  • Patients in Part B taking systemic medications for SLE had to be on a stable dose for at least 3 months before the first study agent infusion
  • Given informed consent and willing and able to adhere to the study visit schedule and other protocol requirements; agreed to avoid alcohol intake; and took adequate measures to prevent pregnancy

Exclusion Criteria:

• Significant history of or concurrent medical condition (other than lupus)
• Use of specific previous or concurrent medications or investigational therapies
• Known or suspected allergy to the study agent or it constituents, having recently donated blood, or having any significant laboratory test values requiring intervention
• Patients with SLE in Part B could not have active central nervous system lupus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, 1 mg/kg CNTO 136	Drug: 1 mg/kg CNTO 136; Type=exact number, unit=mg, number=1, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
Experimental: Part A, 4 mg/kg CNTO 136	Drug: 4 mg/kg CNTO 136; Type=exact number, unit=mg, number=4, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
Experimental: Part A, 10 mg/kg CNTO 136	Drug: 10 mg/kg CNTO 136; Type=exact number, unit=mg, number=10, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
Experimental: Part B, 10 mg/kg CNTO 136/placebo	Drug: 10 mg/kg CNTO 136; Type=exact number, unit=mg, number=10, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.; Drug: Placebo; Form=liquid for infusion, route=intravenous use, every 2 weeks for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events		Up to 26 weeks
Pharmacokinetic profile of CNTO 136	Blood serum concentration over time	Up to 22 weeks
Physical examinations	Assessment of head, eyes, ears, nose and throat, skin and neck, lungs, heart, abdomen, extremities, general neurologic status, and oral examination	Up to 26 weeks
Electrocardiograms (ECGs)		Up to 26 weeks
Sitting blood pressure		Up to 26 weeks
Heart rate		Up to 26 weeks
Respiration rate		Up to 26 weeks
Oral temperature		Up to 26 weeks
Hemoglobin		Up to 26 weeks
Hematocrit		Up to 26 weeks
Platelets and total white blood cells (WBC)		Up to 26 weeks
Albumin and total protein		Up to 26 weeks
Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)		Up to 26 weeks
Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin		Up to 26 weeks
Chloride, potassium, and sodium		Up to 26 weeks
Bicarbonate		Up to 26 weeks
Creatine kinase		Up to 26 weeks
Gamma-glutamyl-transferase		Up to 26 weeks
Glucose		Up to 26 weeks
Lymphocytes and neutrophils		Up to 26 weeks
Inorganic phosphate		Up to 26 weeks
Fasting Lipid Panel	Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.	Up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics evaluations	Percentage change from baseline in serum and plasma biomarker data	Up to 22 weeks
Immune response	The formation of antibodies to CNTO 136	Up to 22 weeks
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)	Measurement of disease activity, scored from 0 (absent) to 70 (severe), and damage, scored from 0 (absent) to 56 (severe)	Up to 22 weeks
British Isles Lupus Assessment Group (BILAG) score	Measures the need for alterations or intensification of therapy. The assessing physician considers each item as to its presence in the past month, and answers 0 = not present, 1 = improving; 2 = same; 3 = worse; or 4 = new.	Up to 22 weeks
SELENA-SLEDAI Flare Composite	Assesses the presence and severity of lupus flare. Scores range from 0 (mild) to 105 (severe).	Up to 22 weeks

Collaborators and Investigators

• Sponsor: Centocor Research & Development, Inc.
• Investigators: Study Director: Centocor Research & Development, Inc., PA, USA Clinical Trial, Centocor Research & Development, Inc.

Publications and helpful links

General Publications

• Szepietowski JC, Nilganuwong S, Wozniacka A, Kuhn A, Nyberg F, van Vollenhoven RF, Bengtsson AA, Reich A, de Vries DE, van Hartingsveldt B, Robinson DW Jr, Gordon R, Hsu B. Phase I, randomized, double-blind, placebo-controlled, multiple intravenous, dose-ascending study of sirukumab in cutaneous or systemic lupus erythematosus. Arthritis Rheum. 2013 Oct;65(10):2661-71. doi: 10.1002/art.38091.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: July 6, 2012
• First Submitted That Met QC Criteria: October 5, 2012
• First Posted (Estimate): October 8, 2012

Study Record Updates

• Last Update Posted (Estimate): October 8, 2012
• Last Update Submitted That Met QC Criteria: October 5, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Systemic lupus erythematosus; Sirukumab; Cutaneous lupus erythematosus; Lupus erythematosus; Human anti-IL 6 monoclonal antibody
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous
• Other Study ID Numbers: CR013000; C0136T03 (Other Identifier: Centocor Research & Development, Inc., PA, USA); 2006-002432-25 (EudraCT Number)