A Study of the Safety and Pharmacokinetics of CNTO 136 in Patients With Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus
Primary Purpose
Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Systemic
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
1 mg/kg CNTO 136
4 mg/kg CNTO 136
10 mg/kg CNTO 136
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Erythematosus, Cutaneous focused on measuring Cutaneous lupus erythematosus, Systemic lupus erythematosus, Lupus erythematosus, Human anti-IL 6 monoclonal antibody, Sirukumab
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A, 1 mg/kg CNTO 136
Part A, 4 mg/kg CNTO 136
Part A, 10 mg/kg CNTO 136
Part B, 10 mg/kg CNTO 136/placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of participants with adverse events
Pharmacokinetic profile of CNTO 136
Blood serum concentration over time
Physical examinations
Assessment of head, eyes, ears, nose and throat, skin and neck, lungs, heart, abdomen, extremities, general neurologic status, and oral examination
Electrocardiograms (ECGs)
Sitting blood pressure
Heart rate
Respiration rate
Oral temperature
Hemoglobin
Hematocrit
Platelets and total white blood cells (WBC)
Albumin and total protein
Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)
Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin
Chloride, potassium, and sodium
Bicarbonate
Creatine kinase
Gamma-glutamyl-transferase
Glucose
Lymphocytes and neutrophils
Inorganic phosphate
Fasting Lipid Panel
Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.
Secondary Outcome Measures
Pharmacodynamics evaluations
Percentage change from baseline in serum and plasma biomarker data
Immune response
The formation of antibodies to CNTO 136
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)
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.
SELENA-SLEDAI Flare Composite
Assesses the presence and severity of lupus flare. Scores range from 0 (mild) to 105 (severe).
Full Information
NCT ID
NCT01702740
First Posted
July 6, 2012
Last Updated
October 5, 2012
Sponsor
Centocor Research & Development, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01702740
Brief Title
A Study of the Safety and Pharmacokinetics of CNTO 136 in Patients With Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus
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 Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centocor Research & Development, Inc.
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Systemic
Keywords
Cutaneous lupus erythematosus, Systemic lupus erythematosus, Lupus erythematosus, Human anti-IL 6 monoclonal antibody, Sirukumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A, 1 mg/kg CNTO 136
Arm Type
Experimental
Arm Title
Part A, 4 mg/kg CNTO 136
Arm Type
Experimental
Arm Title
Part A, 10 mg/kg CNTO 136
Arm Type
Experimental
Arm Title
Part B, 10 mg/kg CNTO 136/placebo
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
1 mg/kg CNTO 136
Intervention Description
Type=exact number, unit=mg, number=1, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
4 mg/kg CNTO 136
Intervention Description
Type=exact number, unit=mg, number=4, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
10 mg/kg CNTO 136
Intervention Description
Type=exact number, unit=mg, number=10, form=powder for solution for infusion, route=intravenous use, every 2 weeks for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form=liquid for infusion, route=intravenous use, every 2 weeks for 6 weeks.
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Time Frame
Up to 26 weeks
Title
Pharmacokinetic profile of CNTO 136
Description
Blood serum concentration over time
Time Frame
Up to 22 weeks
Title
Physical examinations
Description
Assessment of head, eyes, ears, nose and throat, skin and neck, lungs, heart, abdomen, extremities, general neurologic status, and oral examination
Time Frame
Up to 26 weeks
Title
Electrocardiograms (ECGs)
Time Frame
Up to 26 weeks
Title
Sitting blood pressure
Time Frame
Up to 26 weeks
Title
Heart rate
Time Frame
Up to 26 weeks
Title
Respiration rate
Time Frame
Up to 26 weeks
Title
Oral temperature
Time Frame
Up to 26 weeks
Title
Hemoglobin
Time Frame
Up to 26 weeks
Title
Hematocrit
Time Frame
Up to 26 weeks
Title
Platelets and total white blood cells (WBC)
Time Frame
Up to 26 weeks
Title
Albumin and total protein
Time Frame
Up to 26 weeks
Title
Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)
Time Frame
Up to 26 weeks
Title
Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin
Time Frame
Up to 26 weeks
Title
Chloride, potassium, and sodium
Time Frame
Up to 26 weeks
Title
Bicarbonate
Time Frame
Up to 26 weeks
Title
Creatine kinase
Time Frame
Up to 26 weeks
Title
Gamma-glutamyl-transferase
Time Frame
Up to 26 weeks
Title
Glucose
Time Frame
Up to 26 weeks
Title
Lymphocytes and neutrophils
Time Frame
Up to 26 weeks
Title
Inorganic phosphate
Time Frame
Up to 26 weeks
Title
Fasting Lipid Panel
Description
Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.
Time Frame
Up to 8 weeks
Secondary Outcome Measure Information:
Title
Pharmacodynamics evaluations
Description
Percentage change from baseline in serum and plasma biomarker data
Time Frame
Up to 22 weeks
Title
Immune response
Description
The formation of antibodies to CNTO 136
Time Frame
Up to 22 weeks
Title
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)
Description
Measurement of disease activity, scored from 0 (absent) to 70 (severe), and damage, scored from 0 (absent) to 56 (severe)
Time Frame
Up to 22 weeks
Title
British Isles Lupus Assessment Group (BILAG) score
Description
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.
Time Frame
Up to 22 weeks
Title
SELENA-SLEDAI Flare Composite
Description
Assesses the presence and severity of lupus flare. Scores range from 0 (mild) to 105 (severe).
Time Frame
Up to 22 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Centocor Research & Development, Inc., PA, USA Clinical Trial
Organizational Affiliation
Centocor Research & Development, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
23896980
Citation
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.
Results Reference
derived
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A Study of the Safety and Pharmacokinetics of CNTO 136 in Patients With Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus
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