Safety Study of AMG 811 in Subjects With Discoid Lupus Erythematosus

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, placebo-controlled, two-period, crossover study in which approximately 20 subjects with Discoid Lupus Erythematosus will be enrolled to receive AMG 811 and placebo in one of two sequences (ie, AMG 811 followed by placebo or placebo followed by AMG 811).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single Dose, Two-period, Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of AMG 811 in Subjects With Discoid Lupus Erythematosus

Conditions
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Cutaneous Lupus, Discoid Lupus, Lupus, Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: AMG811
* Drug: AMG811 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, between the ages of 18 and 70 years of age, inclusive, at the time of randomization; Diagnosis of discoid lupus erythematosus (DLE) with or without SLE; Intolerance of anti-malarial therapy or ≥ 3 months of anti-malarial therapy with residual disease activity. The total CLASI activity must be ≥ 10; Stable dose of topical steroids no stronger than medium-potency (Class III or less) for ≥ 2 weeks and/or systemic immunosuppressive therapy at stable dose for ≥ 8 weeks prior to randomization (except for leflunomide which requires ≥ 12 weeks) are permitted; Oral prednisone ≤ 20 mg/day (or equivalent) is permitted; one increase or one decrease of ≤ 5 mg/day prednisone equivalent (not to exceed 20 mg/day) will be allowed within 30 days before randomization; Exclusion Criteria: Any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of DLE or SLE) that would, by its progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures per the investigator's discretion; History of malignancy; Signs or symptoms or relevant history of a viral, bacterial, fungal, and parasitic infection, or recent history of repeated infections; Subjects with evidence of past or active tuberculosis Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies (confirmed by PCR or RIBA) during the screening period; Receipt of a live vaccine within 3 months of study randomization and during the study; Prior use of the following agents: Administration of an investigational biologic agent that primarily targets the immune system - Rituximab, Lymphostat-B, or TACl-Ig within 9 months prior to randomization (or comparable B cell depleting or B cell inhibiting biologics); Rituximab (or other depleting CD20 targeted agents) treated patients must demonstrate a return of CD19+ B cells to > 5/μL; CTLA4-Ig within 3 months prior to randomization; Other agents within 5 half-lives prior to randomization; Administration of cyclosporine, tacrolimus, sirolimus, IV immunoglobulin, and/or plasmapheresis within 3 months of randomization; Administration of thalidomide or lenalidomide within 3 months of randomization; Administration of oral or IV cyclophosphamide (or any other alkylating agent) within 9 months of randomization;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AMG811<br>All will receive AMG 811, either on Day 1 or Day 85 | Drug: AMG811<br>* Twelve subjects will be randomized to receive AMG 811 in Period 1 and will receive AMG 811 Placebo in Period 2. The AMG 811 and AMG 811 Placebo will be administered by injection.<br>|
| Placebo Comparator: AMG811 Placebo<br>All will receive placebo, either on Day 1 or Day 85 | Drug: AMG811 Placebo<br>* 8 subjects will be randomized to receive AMG 811 Placebo in Period 1 and will receive AMG 811 in Period 2. The AMG 811 Placebo and AMG 811 will be administered by injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation: Subject incidence of treatment-emergent adverse events, clinically significant changes in vital signs, physical examination endpoints, clinical laboratory safety tests, ECGs and the development of anti-AMG811 antibodies |  | 197 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters, Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score and IFN-gamma related gene expression in skin biopsy samples |  | 197 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus, Discoid Lupus, Cutaneous Lupus