Safety and Tolerability of Intravenous Dose of MEDI-546 in Japanese Subjects With Systemic Lupus Erythematosus.

A Phase 2, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety and Tolerability of Intravenous Dose of MEDI-546, a Human Monoclonal Antibody Directed Against Type I Interferon Receptor (IFNAR), in Japanese Subjects With Active Systemic Lupus Erythematosus (SLE).

The purpose of this study is to assess safety, tolerability, pharmacokinetics and pharmacodynamics of MEDI-546 in Japanese SLE patients.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: MEDI-546; Drug: MEDI-546; Drug: MEDI-546

Detailed Description

A phase 2, multicenter, open-label, dose-escalation study to evaluate the safety and tolerability of intravenous dose of MEDI-546, a human monoclonal antibody directed against type I interferon receptor (IFNAR), in Japanese subjects with active systemic lupus erythematosus (SLE)

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chiba-shi, Japan, 260-8677
    • Research Site
  • Chuo-ku, Japan, 104-8560
    • Research Site
  • Ota-ku, Japan, 143-8541
    • Research Site
  • Sendai-shi, Japan, 980-8574
    • Research Site
  • Shimotsuke-shi, Japan, 329-0498
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Fulfils at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE.
• Weight greater than or equal to 40.0 kg.
• Diagnosis of pediatric or adult SLE with chronic disease activity requiring ongoing treatment or observation for ≥ 24 weeks prior to screening.
• Currently receiving stable dose of oral prednisone and/or antimalarials/immunosuppressives.
• Active moderate to severe SLE disease based on SLE disease activity score.

Exclusion Criteria:

• Active severe or unstable neuropsychiatric SLE.
• Active severe SLE-driven renal disease or unstable renal disease.
• Clinically significant active infection including ongoing and chronic infections.
• Known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus infection or splenectomy that predisposes the subject to infection.
• Confirmed positive tests for hepatitis B or positive test for hepatitis C.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; MEDI-546 100 mg IV	Drug: MEDI-546; Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks; Drug: MEDI-546; Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks; Drug: MEDI-546; Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV.
Experimental: 2; MEDI-546 300 mg IV	Drug: MEDI-546; Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks; Drug: MEDI-546; Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks; Drug: MEDI-546; Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV.
Experimental: 3; MEDI-546 1000 mg IV	Drug: MEDI-546; Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks; Drug: MEDI-546; Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks; Drug: MEDI-546; Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Summary of Adverse Events	Stage I (up to 48 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax		Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29
Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast		Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29
Anti-drug Antibody (ADA)	MEDI-546 antibody detection measured by electrochemiluminescence (ECL).	Stage I (up to Week 48)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: MedImmune LLC
• Investigators: Study Director: Roberta Weiss, MD, MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2012
• Primary Completion (Actual): August 19, 2014
• Study Completion (Actual): February 21, 2017

Study Registration Dates

• First Submitted: March 19, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (Estimate): March 21, 2012

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Systemic Lupus Erythematosus; Tolerability; Japan; Phase2; SLE, MEDI-546
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: D3461C00002