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

Sponsor

Centocor Research & Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01702740

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lupus Erythematosus, Cutaneous Lupus Erythematosus, Systemic	Drug: 1 mg/kg CNTO 136 Drug: 4 mg/kg CNTO 136 Drug: 10 mg/kg CNTO 136 Drug: Placebo	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Oct 1, 2009

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events [Up to 26 weeks]
Pharmacokinetic profile of CNTO 136 [Up to 22 weeks]
Blood serum concentration over time
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
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 [Up to 8 weeks]
Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.

Secondary Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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