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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Systemic

Intervention / Treatment
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* Drug: 1 mg/kg CNTO 136
* Drug: 4 mg/kg CNTO 136
* Drug: 10 mg/kg CNTO 136
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cutaneous lupus erythematosus, Systemic lupus erythematosus, Lupus erythematosus, Human anti-IL 6 monoclonal antibody, Sirukumab