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

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

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.

Official Title
-----------------
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

Conditions
-----------------
Dermatomyositis, Polymyositis, Sjogren's, SLE, SSc

Intervention / Treatment
-----------------
* Biological: MEDI7734
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Age 18-65 years old Diagnoses of dematomyositis, polymyositis, Sjogren's syndrome, systemic lupus erythematosus and/or systemic sclerosis based on standard criteria. Weight 40-120kg 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: History of a hypersensitivity reaction or anaphylaxis to a previous mAb or human immunoglobulin therapy. Chronic hepatitis B, chronic hepatitis C, or HIV infection. History of latent or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening. Herpes zoster infection within 3 months before randomization Any of the following medications within 6 months of Day 1: cyclophosphamide, leflunomide > 20 mg/day, abatacept. Receipt of a mAb within 5 published half-lives prior to Day 1. Receipt of rituximab or an experimental B-cell depleting mAb within 6 months of Day 1. Receipt of rituximab or an experimental B-cell depleting mAb without return of CD19 or CD20 count to above the lower limit of normal. Receipt of alemtuzumab, bone marrow transplantation, stem cell transplantation, total lymphoid irradiation, or T-cell vaccination therapy -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polymyositis, dermatomyositis, Sjogren's syndrome, SLE, SSc