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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01389895




Registration number
NCT01389895
Ethics application status
Date submitted
23/06/2011
Date registered
8/07/2011
Date last updated
10/01/2014

Titles & IDs
Public title
Safety Study of AMG 557 in Subjects With Subacute Cutaneous Lupus Erythematosus
Scientific title
A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of AMG 557 in Subjects With Subacute Cutaneous Lupus Erythematosus
Secondary ID [1] 0 0
20100037
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous Lupus 0 0
Lupus 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 557
Treatment: Drugs - AMG 557 Placebo

Active Comparator: AMG 557 - 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.

Placebo Comparator: AMG 557 Placebo - All will receive placebo on Day 1, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, and Day 99.


Treatment: Drugs: AMG 557
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.

Treatment: Drugs: AMG 557 Placebo
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
253 Days
Secondary outcome [1] 0 0
Determine the pharmacokinetic (PK) profile of AMG 557 after multiple subcutaneous (SC) doses in subacute cutaneous lupus erythematosus (SCLE) subjects.
Timepoint [1] 0 0
253 Days
Secondary outcome [2] 0 0
Characterize the mean change and variability in serum SS-A and SS-B autoantibodies.
Timepoint [2] 0 0
253 Days
Secondary outcome [3] 0 0
Characterize change in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (CLASI-a) score.
Timepoint [3] 0 0
253 Days

Eligibility
Key inclusion criteria
- 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.

-
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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).

- 29. 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;

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Woolloongabba
Recruitment hospital [2] 0 0
Research Site - Carlton
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3053 - Carlton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01389895
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01389895