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

Phase 1

Completed

• Conditions: Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic
• Interventions: Drug: 1 mg/kg CNTO 136; Drug: 4 mg/kg CNTO 136; Drug: 10 mg/kg CNTO 136; Drug: Placebo

• Registration Number: NCT01702740
• Lead Sponsor: Centocor Research & Development, Inc.

Brief Summary

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.

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 Timeline

• Study Start: 2007-03
• Primary Completion: 2009-10
• Study Completion: 2009-10
• Study First Submitted: 2012-07-06
• Status Verified: 2012-10
• Study First Submitted QC: 2012-10-05
• Last Update Submitted: 2012-10-05
• Study First Posted: 2012-10-08
• Last Update Posted: 2012-10-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A, 1 mg/kg CNTO 136	1 mg/kg CNTO 136	-
Part B, 10 mg/kg CNTO 136/placebo	Placebo	-
Part A, 4 mg/kg CNTO 136	4 mg/kg CNTO 136	-
Part B, 10 mg/kg CNTO 136/placebo	10 mg/kg CNTO 136	-
Part A, 10 mg/kg CNTO 136	10 mg/kg CNTO 136	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamics evaluations	Up to 22 weeks	Percentage change from baseline in serum and plasma biomarker data
Immune response	Up to 22 weeks	The formation of antibodies to CNTO 136
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)	Up to 22 weeks	Measurement of disease activity, scored from 0 (absent) to 70 (severe), and damage, scored from 0 (absent) to 56 (severe)
British Isles Lupus Assessment Group (BILAG) score	Up to 22 weeks	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.
SELENA-SLEDAI Flare Composite	Up to 22 weeks	Assesses the presence and severity of lupus flare. Scores range from 0 (mild) to 105 (severe).