Clinical trial NCT01702740: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lupus Erythematosus, Cutaneous
Lupus Erythematosus, Systemic
Keywords: Cutaneous lupus erythematosus
Systemic lupus erythematosus
Lupus erythematosus
Human anti-IL 6 monoclonal antibody
Sirukumab
Lead sponsor: Centocor Research & Development, Inc.
Sponsor class: INDUSTRY
First posted: 2012-10-08
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 26 weeks
measure: Pharmacokinetic profile of CNTO 136
timeFrame: Up to 22 weeks
measure: Physical examinations
timeFrame: Up to 26 weeks
measure: Electrocardiograms (ECGs)
timeFrame: Up to 26 weeks
measure: Sitting blood pressure
timeFrame: Up to 26 weeks
measure: Heart rate
timeFrame: Up to 26 weeks
measure: Respiration rate
timeFrame: Up to 26 weeks
measure: Oral temperature
timeFrame: Up to 26 weeks
measure: Hemoglobin
timeFrame: Up to 26 weeks
measure: Hematocrit
timeFrame: Up to 26 weeks
measure: Platelets and total white blood cells (WBC)
timeFrame: Up to 26 weeks
measure: Albumin and total protein
timeFrame: Up to 26 weeks
measure: Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)
timeFrame: Up to 26 weeks
measure: Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin
timeFrame: Up to 26 weeks
measure: Chloride, potassium, and sodium
timeFrame: Up to 26 weeks
measure: Bicarbonate
timeFrame: Up to 26 weeks
measure: Creatine kinase
timeFrame: Up to 26 weeks
measure: Gamma-glutamyl-transferase
timeFrame: Up to 26 weeks
measure: Glucose
timeFrame: Up to 26 weeks
measure: Lymphocytes and neutrophils
timeFrame: Up to 26 weeks
measure: Inorganic phosphate
timeFrame: Up to 26 weeks
measure: Fasting Lipid Panel
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Pharmacodynamics evaluations
timeFrame: Up to 22 weeks
measure: Immune response
timeFrame: Up to 22 weeks
measure: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)
timeFrame: Up to 22 weeks
measure: British Isles Lupus Assessment Group (BILAG) score
timeFrame: Up to 22 weeks
measure: SELENA-SLEDAI Flare Composite
timeFrame: Up to 22 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Centocor Research & Development, Inc.
name: Centocor Research & Development, Inc., PA, USA Clinical Trial
role: STUDY_DIRECTOR
References:
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.