Safety Study of AMG 557 in Subjects With Subacute Cutaneous Lupus Erythematosus

NCT01389895 | Terminated Phase 1

• 1 other identifier: 20100037
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 10

Brief Summary

This study will be a multicenter, randomized, double-blind, placebo-controlled, multiple dose study in which approximately 24 subjects with SCLE will be enrolled. Cohort 1 will consist of 12 subjects (6 AMG 557: 6 placebo) randomized to receive AMG 557 210 mg or matching placebo. Cohort 2 will consist of 12 subjects (6 AMG 557: 6 placebo) randomized to receive AMG 557 140 mg or matching placebo. Enrollment of Cohort 2 (140 mg) will be initiated after enrollment of Cohort 1 (210 mg) is completed.

Conditions

Cutaneous Lupus; Lupus

Keywords

Lupus; Cutaneous lupus

Outcome Measures

Primary Outcomes (1)

• Safety evaluation: Subject incidence of treatment-emergent adverse events, vital signs, physical examinations, clinical laboratory safety tests, ECGs, and the incidence of binding and neutralizing antibodies to AMG 557

  253 Days

Secondary Outcomes (3)

• Determine the pharmacokinetic (PK) profile of AMG 557 after multiple subcutaneous (SC) doses in subacute cutaneous lupus erythematosus (SCLE) subjects.

  253 Days

• Characterize the mean change and variability in serum SS-A and SS-B autoantibodies.

  253 Days

• Characterize change in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (CLASI-a) score.

  253 Days

Study Arms (2)

AMG 557

ACTIVE COMPARATOR

All will receive AMG 557 on Day 1, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, and Day 99.

Drug: AMG 557

AMG 557 Placebo

PLACEBO COMPARATOR

All will receive placebo on Day 1, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, and Day 99.

Drug: AMG 557 Placebo

Interventions

AMG 557 DRUG

AMG 557 (210 mg) or (140 mg ) will be administered as subcutaneous injections in the anterior abdomen of the subjects. Twelve subjects will be randomized to receive AMG 557. Beginning on Day 1, subjects will receive either 210 mg AMG 557 or 140 mg AMG 557 once weekly for 3 weeks on Day 1, Day 8, and Day 15 and following with 6 additional doses of AMG 557 every other week on Day 29, Day 43, Day 57, Day 71, Day 85, and Day 99. Subjects will be followed out to Day 253 for safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) assessments.

AMG 557

AMG 557 Placebo DRUG

AMG 557 Placebo (210 mg) or (140 mg )will be administered as subcutaneous injections in the anterior abdomen of the subjects. Twelve subjects will be randomized to receive placebo. Beginning on Day 1, subjects will receive placebo once weekly for 3 weeks on Day 1, Day 8, and Day 15 and following with 6 additional doses of placebo every other week on Day 29, Day 43, Day 57, Day 71, Day 85, and Day 99. Subjects will be followed out to Day 253 for safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) assessments.

AMG 557 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;
• Body mass index from 18 to 35 kg/m2 at screening;
• Diagnosis of subacute cutaneous lupus erythematosus (SCLE) with or without systemic lupus erythematosus (SLE). SCLE as defined by the Gilliam and Sontheimer classification (J Am Acad Dermatol 1981; 4(4):471-475). SLE is defined by the most recent American College of Rheumatology criteria, including positive antinuclear antibodies (ANA) during screening or by documented history (at least 1:80 by indirect immunofluorescent assay);
• A history of skin biopsy consistent with the diagnosis of SCLE;
• Positive SS-A and/or SS-B antibodies at screening;
• Intolerance of anti-malarial therapy or ≥ 3 months of anti-malarial therapy with residual disease activity as defined by: at least 2 areas with at least level 2 erythema or 3 areas with at least level 1 erythema using cutaneous lupus erythematosus disease area and severity index (CLASI). The total CLASI activity must be ≥ 10;
• Subject must have stable disease activity for 3 months prior to screening in the clinical judgment of the Principal Investigator (PI) with no anticipated changes in therapy;
• Stable dose of topical steroids no stronger than medium-potency (Class III or Class VII) for ≥ 2 weeks from screening is permitted;
• Prednisone ≤ 10 mg/day (or equivalent) is permitted;
• Stable doses of methotrexate ≤ 20 mg/week, azathioprine ≤ 150 mg/day, and 6-mercaptopurine ≤ 150 mg/day for 12 weeks prior to screening are permitted.

You may not qualify if:

• Drug-induced SCLE;
• Any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of SCLE, SLE, or Sjögren's syndrome) that would, by its progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures per the investigator's discretion. This includes any age related co-morbidities such as presence of congestive heart failure, angina, chronic obstructive pulmonary disease, and asthma;
• Presence or history of vasculitis (comprising internal organs or extremities or leading to peripheral neuropathy) within the last 3 years, presence or history of active Central Nervous System (CNS) lupus (defined as seizure disorder, cerebral vascular accident, psychosis ascribed to SLE , encephalitis, meningitis, and myelitis) requiring therapy within the last 3 years;
• History of malignancy;
• Signs or symptoms of a viral, bacterial or fungal infection within 30 days of study randomization, or recent history of repeated infections;
• Underlying condition other than SCLE, SLE, Sjögren's syndrome that predisposes one to infections (eg, history of splenectomy);
• Administration of \>10 mg/day prednisone (or equivalent) in the 30 days prior to randomization;
• Prior use of any following biological agents: Rituximab, Lymphostat-B, TACl-Ig, and CTLA4-Ig;
• Current treatment (within 3 months or 5 half-lives of screening) with thalidomide, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, Intravenous (IV) immunoglobulin, plasmapheresis, oral or IV cyclophosphamide;
• Receiving or has received any investigational drug (or is currently using an investigational device) within the 30 days or 5 half-lives (whichever is longer), prior to receiving the first dose of study medication).
• \. Use of any other over-the-counter or prescription medications within the 14 days or 5 half-lives (whichever is longer), prior to receiving the first dose of study medication. Acetaminophen (up to 2 g per day) for analgesia and hormone replacement therapy (eg, estrogen, thyroid) will be allowed. In addition, prescription drugs for hypertension or hypercholesterolemia, oral hypoglycemic drugs, or NSAIDs will be allowed; however, NSAIDS are not permitted within 24 hours of skin biopsies to reduce the risk of bleeding. Other medications may be approved following review by the Principal Investigator and the Amgen Medical Monitor. Written documentation of this review and Amgen acknowledgement is required for subject participation;

Sponsors & Collaborators

• Amgen: lead

Study Sites (10)

Research Site

Birmingham, Alabama, 35233, United States

Location

Research Site

Ann Arbor, Michigan, 48103, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Austin, Texas, 78705, United States

Location

Research Site

Dallas, Texas, 75231, United States

Location

Unknown Facility

Dallas, Texas, 75231, United States

Location

Research Site

Dallas, Texas, 75235, United States

Location

Research Site

Woolloongabba, Queensland, 4102, Australia

Location

Research Site

Carlton, Victoria, 3053, Australia

Location

Research Site

Peterborough, Ontario, K9J 1Z2, Canada

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

AMG 557

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: July 8, 2011
• Study Start: October 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: January 10, 2014

Record last verified: 2014-01

Locations

CA (1); AU (2); US (7)