A Safety and Tolerability Study of MEDI-570 in Systemic Lupus Erythematosus

A Phase 1, Double-blind, Randomized, Single Ascending Dose Study of the Safety and Tolerability of MEDI-570 in SLE

The purpose of this study is to evaluate the safety and tolerability of MEDI-570 in adult subjects with moderately to severely active systemic lupus erythematosus (SLE).

Study Overview

• Status: Terminated
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Other: Placebo; Biological: MEDI-570 0.03 MG; Biological: MEDI-570 0.1 MG; Biological: MEDI-570 0.3 MG; Biological: MEDI-570 1 MG

Detailed Description

This is a Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and tolerability of escalating single subcutaneous doses of MEDI-570 in adult subjects with moderately to severely active SLE.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada
      • Research Site
• Mexico
  • Chihuahua, Mexico
    • Research Site
  • Guadalajara, Mexico
    • Research Site
  • Mexico, Mexico
    • Research Site
• Peru
  • Lima, Peru
    • Research Site
  • Trujillo, Peru
    • Research Site
• South Africa
  • Cape Town, South Africa
    • Research Site
  • Johannesburg, South Africa
    • Research Site
• United States
  • California
    • Long Beach, California, United States
      • Research Site
    • San Leandro, California, United States
      • Research Site
  • Florida
    • Ft. Lauderdale, Florida, United States
      • Research Site
    • Ocala, Florida, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
  • Michigan
    • Lansing, Michigan, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
  • North Carolina
    • Winston-Salem, North Carolina, United States
      • Research Site
  • Ohio
    • Columbus, Ohio, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meet or have met at least 4 of the 11 revised American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE)
• Score greater than or equal to (>=) 6 points on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at Screening
• Ability to complete the study period, including follow-up period through Day 169
• Willingness to forego other forms of experimental treatment during the study.

Exclusion Criteria:

• History of cancer except basal cell carcinoma treated with apparent success with curative therapy >=1 year before randomization into the study
• Evidence of active or latent tuberculosis (TB)
• History of primary immunodeficiency
• Evidence of infection at any time with hepatitis B or C virus or human immunodeficiency virus (HIV)-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at Screening
• History of sepsis or serious, recurrent, chronic infection, current signs and symptoms of clinically significant chronic infection, or recent (within 6 months before Baseline visit) serious infection
• Any history or evidence of opportunistic infection within 6 months of Screening including severe cytomegalovirus (CMV) or herpetic infections (such as disseminated herpes, herpes encephalitis, ophthalmic herpes)
• Receipt of cyclophosphamide (intravenous or oral) within 6 months of Screening
• Have any absolute contraindications to skin punch biopsies, for example, a history of coagulation disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; A single double-blind dose of placebo matched to MEDI-570 subcutaneous injection on Day 1.	Other: Placebo; A single double-blind dose of placebo matched to MEDI-570 subcutaneous injection on Day 1.
Experimental: MEDI-570 0.03 MG; A single open-label dose of MEDI-570, 0.03 milligram (mg) subcutaneous injection on Day 1.	Biological: MEDI-570 0.03 MG; A single open-label dose of MEDI-570, 0.03 milligram (mg) subcutaneous injection on Day 1.
Experimental: MEDI-570 0.1 MG; A single open-label dose of MEDI-570, 0.1 mg subcutaneous injection on Day 1.	Biological: MEDI-570 0.1 MG; A single open-label dose of MEDI-570, 0.1 mg subcutaneous injection on Day 1.
Experimental: MEDI-570 0.3 MG; A single double-blind dose of MEDI-570, 0.3 mg subcutaneous injection on Day 1.	Biological: MEDI-570 0.3 MG; A single double-blind dose of MEDI-570, 0.3 mg subcutaneous injection on Day 1.
Experimental: MEDI-570 1 MG; A single double-blind dose of MEDI-570, 1 mg subcutaneous injection on Day 1.	Biological: MEDI-570 1 MG; A single double-blind dose of MEDI-570, 1 mg subcutaneous injection on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 169 that were absent before treatment or that worsened relative to pretreatment state.	Day 1 to Day 169

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameters for MEDI-570	Following pharmacokinetic parameters were to be evaluated by using non-compartmental analysis: t1/2 = terminal phase elimination half-life which is the time measured for the serum concentration to decrease by one half; tmax = time to maximum observed serum concentration; Cmax = maximum observed serum concentration; AUC (0-t) = area under the serum concentration-time curve from time 0 to last measurable concentration; AUC (0-infinity) = area under the serum concentration-time curve from time 0 to extrapolated infinite time obtained from AUC (0-t) plus AUC (t-infinity); Vz/F = apparent volume of distribution, which is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug; CL/F = apparent clearance which is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Predose and postdose on Day 1; Day 3, 5, 8, 15, 29, 57, 85, 113, 141, and 169
Number of Participants With Anti-Drug Antibodies to MEDI-570 at Any Visit		Predose on Day 1; Day 85, 113, and 169

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: AstraZeneca
• Investigators: Study Director: David Close, PhD, MedImmune Ltd

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: April 14, 2010
• First Submitted That Met QC Criteria: May 19, 2010
• First Posted (Estimate): May 20, 2010

Study Record Updates

• Last Update Posted (Estimate): August 26, 2014
• Last Update Submitted That Met QC Criteria: August 11, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: SLE; Systemic lupus erythematosus; MEDI-570
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: MI-CP209