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

Lupus Erythematosus, Systemic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01702740
• Other study ID #: CR013000
• Secondary ID: C0136T032006-002
• Status: Completed
• Phase: Phase 1
• First received: July 6, 2012
• Last updated: October 5, 2012
• Start date: March 2007
• Est. completion date: October 2009

Study information

• Verified date: October 2012
• Source: Centocor Research & Development, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Cutaneous
• Lupus Erythematosus, Systemic

Intervention

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.
• 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.
• 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.
• Placebo
Form=liquid for infusion, route=intravenous use, every 2 weeks for 6 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Centocor Research & Development, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events		Up to 26 weeks	No
Primary	Pharmacokinetic profile of CNTO 136	Blood serum concentration over time	Up to 22 weeks	No
Primary	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	No
Primary	Electrocardiograms (ECGs)		Up to 26 weeks	No
Primary	Sitting blood pressure		Up to 26 weeks	No
Primary	Heart rate		Up to 26 weeks	No
Primary	Respiration rate		Up to 26 weeks	No
Primary	Oral temperature		Up to 26 weeks	No
Primary	Hemoglobin		Up to 26 weeks	No
Primary	Hematocrit		Up to 26 weeks	No
Primary	Platelets and total white blood cells (WBC)		Up to 26 weeks	No
Primary	Albumin and total protein		Up to 26 weeks	No
Primary	Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)		Up to 26 weeks	No
Primary	Blood urea nitrogen (BUN), calcium, creatinine, and total bilirubin		Up to 26 weeks	No
Primary	Chloride, potassium, and sodium		Up to 26 weeks	No
Primary	Bicarbonate		Up to 26 weeks	No
Primary	Creatine kinase		Up to 26 weeks	No
Primary	Gamma-glutamyl-transferase		Up to 26 weeks	No
Primary	Glucose		Up to 26 weeks	No
Primary	Lymphocytes and neutrophils		Up to 26 weeks	No
Primary	Inorganic phosphate		Up to 26 weeks	No
Primary	Fasting Lipid Panel	Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and triglycerides.	Up to 8 weeks	No
Secondary	Pharmacodynamics evaluations	Percentage change from baseline in serum and plasma biomarker data	Up to 22 weeks	No
Secondary	Immune response	The formation of antibodies to CNTO 136	Up to 22 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	SELENA-SLEDAI Flare Composite	Assesses the presence and severity of lupus flare. Scores range from 0 (mild) to 105 (severe).	Up to 22 weeks	No