A Study to Evaluate Safety and Tolerability of IV or SC Dose of MEDI-545 in Patients With Systemic Lupus Erythematosus.

A Phase II, Multicenter, Open-Label, Dose-Escalation Study to Evaluate Safety and Tolerability of IV or SC Dose of MEDI-545, a Fully Human Monoclonal Antibody Directed Against Interferon Alpha Subtypes, in Japanese Patients Who Have Systemic Lupus Erythematosus (SLE)

The purpose of the study is to evaluate the safety and tolerability of MEDI-545 in Japanese adult SLE patients. This will be done by collecting the data from 3 cohorts of IV doses and 1 cohort of SC doses.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: MEDI-545; Drug: MEDI-545; Drug: MEDI-545; Drug: MEDI-545; Drug: MEDI-545; Drug: MEDI-545 600

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chiba-shi, Japan, 260-8712
    • Research Site
  • Fukuoka-shi, Japan, 810-8563
    • Research Site
  • Kanazawa-shi, Japan, 920-8650
    • Research Site
  • Kawagoe-shi, Japan, 350-8550
    • Research Site
  • Kitakyushu-shi, Japan, 807-8555
    • Research Site
  • Sapporo-shi, Japan, 060-8638
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have previously met ≥4 of the 11 revised ACR criteria
• Have positive antinuclear antibody test (ANA) at ≥1:80 serum dilute in the past or at screening
• Have at least 1 system with a score of A or 2 systems with a score of B on the BILAG index at screening, or have a SELENA-SLEDAI score ≥6

Exclusion Criteria:

• Have received prednisone >20 mg/day (or an equivalent dose of another oral corticosteroid) within 14 days before Visit 2 (Day 1)

• Have received the following medications within 28 days before Visit 2 (Day 1):

  • Systemic cyclophosphamide at any dose
  • Cyclosporine at any dose
  • Tacrolimus at any dose
  • Thalidomide at any dose
  • Mycophenolate mofetil >2 g/day
  • Methotrexate >15 mg/week
  • Azathioprine >2 mg/kg/day
• Women who have a positive pregnancy test (serum hCG) at Visit 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI-545 1.0 mg/kg; Cohort 1	Drug: MEDI-545; Stage I: MEDI-545 1.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 1.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 3.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 3.0 mg/kg IV once every 2 weeks for a total of 79 doses; Drug: MEDI-545; Stage I: MEDI-545 10.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 10.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 100 mg SC, on Day 1 and weekly or once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 100 mg SC once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 1,200 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 1,200 mg IV once every 4 weeks for a total of 40 doses
Experimental: MEDI-545 3.0 mg/kg; Cohort 2	Drug: MEDI-545; Stage I: MEDI-545 1.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 1.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 3.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 3.0 mg/kg IV once every 2 weeks for a total of 79 doses; Drug: MEDI-545; Stage I: MEDI-545 10.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 10.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 100 mg SC, on Day 1 and weekly or once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 100 mg SC once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 1,200 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 1,200 mg IV once every 4 weeks for a total of 40 doses
Experimental: MEDI-545 10.0 mg/kg; Cohort 3	Drug: MEDI-545; Stage I: MEDI-545 1.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 1.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 3.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 3.0 mg/kg IV once every 2 weeks for a total of 79 doses; Drug: MEDI-545; Stage I: MEDI-545 10.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 10.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 100 mg SC, on Day 1 and weekly or once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 100 mg SC once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 1,200 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 1,200 mg IV once every 4 weeks for a total of 40 doses
Experimental: MEDI-545 100 mg; Cohort 4	Drug: MEDI-545; Stage I: MEDI-545 1.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 1.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 3.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 3.0 mg/kg IV once every 2 weeks for a total of 79 doses; Drug: MEDI-545; Stage I: MEDI-545 10.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 10.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 100 mg SC, on Day 1 and weekly or once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 100 mg SC once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 1,200 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 1,200 mg IV once every 4 weeks for a total of 40 doses
Experimental: MEDI-545 600 mg; Cohort 5	Drug: MEDI-545 600; Stage I: MEDI-545 600 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 600 mg IV once every 4 weeks for a total of 40 doses.
Experimental: MEDI-545 1,200 mg; Cohort 6	Drug: MEDI-545; Stage I: MEDI-545 1.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 1.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 3.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 3.0 mg/kg IV once every 2 weeks for a total of 79 doses; Drug: MEDI-545; Stage I: MEDI-545 10.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 10.0 mg/kg IV once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 100 mg SC, on Day 1 and weekly or once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 100 mg SC once every 2 weeks for a total of 79 doses.; Drug: MEDI-545; Stage I: MEDI-545 1,200 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 1,200 mg IV once every 4 weeks for a total of 40 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Each Category of Adverse Events in Stage I	Stage I (up to 1 year)
Number of Participants in Each Category of Adverse Events (AE) in Stage II	Stage II (1 year to 3.5 years after first dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Undre Curve (AUC) of MEDI-545 After First Dose in Stage I		After first dose in Stage I (0 upto 28 days)
AUC0-14 of MEDI-545 After First Dose in Stage I	Summary of area under the concentration-time curve from zero to Day 14.	After first dose in Stage I
Maximum Observed Concentration (Cmax) of MEDI-545 After First Dose in Stage I		After first dose in Stage I
Change From Baseline in 21-gene Signature Fold Change in Stage I	21-gene signature fold change is pharmacodynamics (PD) parameter measuring expression of type I IFN-inducible gene.	Stage I
Number of Participants With Positive Anti-drug Antibody (ADA) During Stage I		Stage I

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: MedImmune LLC
• Investigators: Principal Investigator: Tsutomu Takeuchi, Department of Internal Medicine School of Medicine Keio University; Principal Investigator: Yoshiya Tanaka, The University Hospital, University of Occupational and Environmental Health, Japan

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2009
• Primary Completion (Actual): November 7, 2012
• Study Completion (Actual): July 11, 2016

Study Registration Dates

• First Submitted: December 11, 2009
• First Submitted That Met QC Criteria: December 13, 2009
• First Posted (Estimate): December 15, 2009

Study Record Updates

• Last Update Posted (Actual): November 19, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Immune System Diseases; tolerability; safety; Japanese; Systemic Lupus Erythematosus; Autoimmune Disease; MEDI-545; phase 2
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal; Sifalimumab
• Other Study ID Numbers: D2800C00001