Safety Study of AMG 811 in Subjects With Discoid Lupus Erythematosus

NCT01164917 | Terminated Phase 1

• 1 other identifier: 20100011
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

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).

Conditions

Cutaneous Lupus; Discoid Lupus; Lupus; Systemic Lupus Erythematosus

Keywords

Lupus; Discoid Lupus; Cutaneous Lupus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

AMG811

ACTIVE COMPARATOR

All will receive AMG 811, either on Day 1 or Day 85

Drug: AMG811

AMG811 Placebo

PLACEBO COMPARATOR

All will receive placebo, either on Day 1 or Day 85

Drug: AMG811 Placebo

Interventions

AMG811 DRUG

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.

AMG811

AMG811 Placebo DRUG

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

AMG811 Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Amgen: lead

Study Sites (8)

Research Site

Santa Monica, California, 90404, United States

Location

Research Site

Stanford, California, 94305, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Ann Arbor, Michigan, 48103, United States

Location

Research Site

Durham, North Carolina, 27710, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Dallas, Texas, 75231, United States

Location

Research Site

Salt Lake City, Utah, 84107, United States

Location

Related Publications (1)

• 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.

  PMID: 28118537 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Lupus Erythematosus, Cutaneous; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 19, 2010
• Study Start: August 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: March 1, 2013
• Last Updated: September 16, 2014

Record last verified: 2014-09

Locations

US (8)