Clinical trial NCT01164917: Safety Study of AMG 811 in Subjects With Discoid Lupus Erythematosus
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cutaneous Lupus
Discoid Lupus
Lupus
Systemic Lupus Erythematosus
Keywords: Lupus
Discoid Lupus
Cutaneous Lupus
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-07-19
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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;

Primary outcomes:
measure: 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
timeFrame: 197 days
Secondary outcomes:
measure: PK parameters, Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score and IFN-gamma related gene expression in skin biopsy samples
timeFrame: 197 days
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Werth VP, Fiorentino D, Sullivan BA, Boedigheimer MJ, Chiu K, Wang C, Arnold GE, Damore MA, Bigler J, Welcher AA, Russell CB, Martin DA, Chung JB. Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-gamma Antibody, in Patients With Discoid Lupus Erythematosus. Arthritis Rheumatol. 2017 May;69(5):1028-1034. doi: 10.1002/art.40052. Epub 2017 Mar 31.