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A Study of AMG 557 in Adults With Systemic Lupus Erythematosus
This study is enrolling participants by invitation only.
Sponsored by: Amgen
Information provided by: Amgen
ClinicalTrials.gov Identifier: NCT00774943
  Purpose

This is a Phase 1, randomized, placebo-controlled, double-blind, dose-escalation study of repeat SC doses of AMG 557 in adults with Systemic Lupus Erythematosus.


Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: AMG 557
Phase I

MedlinePlus related topics: Lupus
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Factorial Assignment, Safety Study
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Ascending, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 557 in Subjects With Systemic Lupus Erythematosus

Further study details as provided by Amgen:

Primary Outcome Measures:
  • Subject incidence of treatment-emergent adverse events and the incidence of antibodies to AMG 557. [ Time Frame: Throughout study period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serum PK profile of AMG 557 after multiple dose administrations. Biomarkers of pharmacodynamic activity for AMG 557. [ Time Frame: Throughout study period ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: December 2008
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
AMG 557: Active Comparator Drug: AMG 557
A total of 4 cohorts will be administered multiple doses of drug or placebo subcutaneously. Dose escalation will take place by cohort.
Placebo: Placebo Comparator Drug: AMG 557
A total of 4 cohorts will be administered multiple doses of drug or placebo subcutaneously. Dose escalation will take place by cohort.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Before any study-specific procedure, the appropriate written informed consent must be obtained;
  • Men and women, between the ages of 18 and 70 years old, inclusive, at the time of randomization;
  • Diagnosis of SLE as defined by the most recent ACR criteria, including a positive ANA at screening or documented positive ANA (the titer should be at least 1:80) in the past.
  • SLE duration of at least six months, as diagnosed by a physician;
  • Stable disease, defined as no change in SLE therapy within the previous 30 days; and, in the opinion of the investigator, no anticipated need for a change in SLE therapy will be required while the subject is enrolled in the study;
  • Normal or clinically acceptable ECG (12-lead reporting ventricular rate and PR, QRS, QT, QTc) at screening and Day -1 based on the opinion of the investigator;
  • Body mass index from 18 to 40 kg/m2 at screening;
  • Able and willing to complete entire study according to study schedule.
  • Immunizations up to date, with a minimum of tetanus, diphtheria, pertussis (td/Tdap), pneumococcal (polysaccharide) and influenza (during flu season) vaccinations, as determined by the Principal Investigator.

Exclusion Criteria:

  • Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies (confirmed by PCR or RIBA);
  • Have had signs or symptoms of a viral, bacterial or fungal infection within 30 days of study randomization;
  • Evidence of active or latent tuberculosis as assessed by PPD or Quantiferon testing at screening;
  • Have donated blood or experienced a loss of blood >500mL within 4 weeks of randomization;
  • History of ethanol or drug abuse within the last one year prior to randomization;
  • Evidence of significant renal insufficiency, defined by:

The glomerular fitration rate < 50 mL/min using the Cockroft and Gault equation;

  • Evidence of liver disease (eg, serum ALT or AST > 2x upper limit of normal);
  • Total WBC <3000 x 106/L;
  • Neutrophil count < 1500 x106/L
  • Platelet count <75,000 x 106/L
  • Hemoglobin <10g/dL
  • Any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of SLE) that would, by it progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures in the medical judgment of the investigator. This includes any age related co-morbidites such as presence of congestive heart failure, angina, chronic obstructive pulmonary disease, asthma, and malignancies (other than resected squamous and basal cell carcinoma of the skin).
  • 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 CNS lupus (defined as seizure disorder, cerebral vascular accident, psychosis ascribed to SLE , encephalitis, meningitis, and myelitis) requiring therapy within the last 3 years;
  • Uncontrolled hypertension (Blood pressure > 150/95);
  • Poorly controlled diabetes (HbA1c > 8%);
  • Any history of granulomatous disease including autoimmune granulomatous vasculitis and sarcoidosis;
  • Underlying condition that predisposes the subject to infections (eg, history of splenectomy);
  • Any disorder or condition that prevents the subject from providing truly informed consent;
  • Prior administration of any other biologic that primarily targets the immune system (eg, Lymphostat-B, TACI-Ig, or CTLA4-Ig) in the past 9 months. This includes prior administration of AMG 557;
  • Presence of AMG 557 anti-bodies;
  • Prior administration of rituximab > 9 months with CD19+ B cells <5/µL;
  • Administration of cyclophosphamide (or any other alkylating agent), cyclosporine, tacrolimus, or sirolimus, or > 100 mg/day prednisone or equivalent in the 6 months prior to randomization;
  • Participated in an investigational drug trial involving a monoclonal antibody (not targeting the immune system) within 3 months or 5 half-lives, whichever time period is longer, prior to randomization;
  • Participated in any another investigational drug or device trial within the previous 30 days or 5 half-lives, whichever time period is longer, prior to randomization;
  • Administration of >10 mg/day prednisone (or equivalent) in the 30 days prior to randomization;
  • Known sensitivity to mammalian derived products;
  • Unwilling to practice an effective method of double-barrier contraception as determined by the investigator for the duration of the study;
  • Positive serum hCG at screening or positive urine hCG on D-1; or females who are currently lactating;
  • Known allergies to shellfish or any excipients found in KLH;
  • Previous immunization with KLH.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00774943

Locations
United States, Pennsylvania
Research Site
Duncansville,, Pennsylvania, United States
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

AmgenTrials clinical trials website  This link exits the ClinicalTrials.gov site

Responsible Party: Amgen Inc. ( Global Development Leader )
Study ID Numbers: 20060169
Study First Received: October 16, 2008
Last Updated: December 11, 2008
ClinicalTrials.gov Identifier: NCT00774943  
Health Authority: Canada: Health Canada;   United Kingdom: Medicines and Healthcare Products Regulatory Agency;   United States: Food and Drug Administration

Keywords provided by Amgen:
Systemic lupus erythematosus
ICOSL
B7RP-1
Costimulation

Study placed in the following topic categories:
Autoimmune Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases

Additional relevant MeSH terms:
Immune System Diseases

ClinicalTrials.gov processed this record on January 16, 2009