A Study of AMG 557 in Adults With Systemic Lupus Erythematosus

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00774943
• Date of registration: 16/10/2008
• Prospective Registration: Yes
• Primary sponsor: Amgen
• Public title: A Study of AMG 557 in Adults With Systemic Lupus Erythematosus
• Scientific 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
• Date of first enrolment: December 2008
• Target sample size: 58
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00774943
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Canada, United States

Contacts

• Name: MD
• Affiliation: Amgen

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: AMG 557

Primary Outcome(s)

Subject incidence of treatment-emergent adverse events and the incidence of antibodies to AMG 557. [Time Frame: Throughout study period]

Secondary Outcome(s)

Serum PK profile of AMG 557 after multiple dose administrations. Biomarkers of pharmacodynamic activity for AMG 557. [Time Frame: Throughout study period]

Secondary ID(s)

20060169

Source(s) of Monetary Support

Please refer to primary and secondary sponsors