A Phase 1 Study of MEDI7734 in Type I Interferon-Mediated Autoimmune Diseases

A Phase 1, Randomized, Blinded, Single-Dose, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of MEDI7734 in Type I Interferon-Mediated Autoimmune Diseases

To evaluate the safety and tolerability of escalating, single subcutaneous doses of MEDI7734 in adult subjects with type I interferon-mediated autoimmune diseases.

Study Overview

• Status: Completed
• Conditions: Dermatomyositis, Polymyositis, Sjogren's, SLE, SSc
• Intervention / Treatment: Biological: MEDI7734; Biological: Placebo

Detailed Description

MEDI7734 is a human monoclonal antibody that binds to and causes temporary depletion of plasmacytoid dendritic cells (pDCs), a type of white blood cell. The objectives of this study are to evaluate the safety, drug levels, and pDC levels in subjects who are given a single injection of MEDI7734 or a placebo.

The study will be conducted in subjects with at least one of the five following autoimmune diseases: dermatomyositis, polymyositis, Sjogren's syndrome, systemic lupus erythematosus, or systemic sclerosis.

After a screening period, subjects will be randomized in a 3:1 ratio to receive a single dose of MEDI7734 or matching placebo, administered as a subcutaneous (under the skin) injection. After that, subjects will be evaluated periodically at the study site over at least the next 85 days.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
    • Birmingham, Alabama, United States, 35294
      • Research Site
  • Connecticut
    • Danbury, Connecticut, United States, 6810
      • Research Site
  • Florida
    • DeBary, Florida, United States, 32713
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Miami Springs, Florida, United States, 33166
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Age 18-65 years old
2. Diagnoses of dematomyositis, polymyositis, Sjogren's syndrome, systemic lupus erythematosus and/or systemic sclerosis based on standard criteria.
3. Weight 40-120kg
4. Stable disease such that in the opinion of the investigator it is unlikely that a change in subject's therapeutic regimen would be required during the subsequent 3 months.

Key Exclusion Criteria:

1. History of a hypersensitivity reaction or anaphylaxis to a previous mAb or human immunoglobulin therapy.
2. Chronic hepatitis B, chronic hepatitis C, or HIV infection.
3. History of latent or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening.
4. Herpes zoster infection within 3 months before randomization
5. Any of the following medications within 6 months of Day 1: cyclophosphamide, leflunomide > 20 mg/day, abatacept.
6. Receipt of a mAb within 5 published half-lives prior to Day 1.
7. Receipt of rituximab or an experimental B-cell depleting mAb within 6 months of Day 1.
8. Receipt of rituximab or an experimental B-cell depleting mAb without return of CD19 or CD20 count to above the lower limit of normal.
9. Receipt of alemtuzumab, bone marrow transplantation, stem cell transplantation, total lymphoid irradiation, or T-cell vaccination therapy -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MEDI7734; Three subjects (cohort 1) and six subjects (cohort 2-5) will receive MEDI7734 for a total of 27 subjects.	Biological: MEDI7734; Three subjects (cohort 1) and six subjects (cohort 2-5) will receive MEDI7734 for a total of 27 subjects.
Placebo Comparator: Placebo; One subject (cohort 1) and two subjects (cohort 2-5) will receive placebo, for a total of 9 subjects.	Biological: Placebo; One subject (cohort 1) and two subjects (cohort 2-5) will receive placebo, for a total of 9 subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Event	The safety and tolerability of MEDI7734 as measured by the incidence of any adverse events that occur on or after the day of administration of investigational product through the end of follow-up. Laboratory measurements, vital sign measurements, and electrocardiogram (ECG) parameters will also be evaluated as part of safety.	Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-drug antibodies	Presence of anti-drug antibodies (ADA)	Day 85
Pharmacokinetics Cmax	Maximum concentration of drug achieved	Day 85
Pharmacokinetics Tmax	Time at which maximum concentration of drug is achieved	Day 85
Pharmacokinetic	Half Life	Day 85
Pharmacokinetic	AUC	Day 85
Pharmacodynamics	Blood levels of plasmacytoid cells.	Day 85

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type I Interferon signature	Neutralization ratio of the type I IFN signature	Day 85

Collaborators and Investigators

• Sponsor: Viela Bio
• Collaborators: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2016
• Primary Completion (Actual): October 23, 2017
• Study Completion (Actual): November 27, 2017

Study Registration Dates

• First Submitted: May 3, 2016
• First Submitted That Met QC Criteria: May 19, 2016
• First Posted (Estimate): May 23, 2016

Study Record Updates

• Last Update Posted (Actual): December 21, 2018
• Last Update Submitted That Met QC Criteria: December 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Polymyositis, dermatomyositis, Sjogren's syndrome, SLE, SSc
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Immune System Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Dermatomyositis; Autoimmune Diseases; Polymyositis
• Other Study ID Numbers: D6080C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AstraZeneca's policy is to share data with researchers if the request is in scope of our policy. Additional information can be found on astrazenecaclinicaltrials.com.