Safety Study of AMG 811 in Subjects With Systemic Lupus Erythematosus With and Without Glomerulonephritis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00818948
• Date of registration: 18/12/2008
• Prospective Registration: Yes
• Primary sponsor: Amgen
• Public title: Safety Study of AMG 811 in Subjects With Systemic Lupus Erythematosus With and Without Glomerulonephritis
• Scientific title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 811 in Subjects With Systemic Lupus Erythematosus With and Without Glomerulonephritis
• Date of first enrolment: March 2009
• Target sample size: 56
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00818948
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

France, Hong Kong, Malaysia, Mexico, Singapore, United States

Contacts

• Name: MD
• Affiliation: Amgen

Key inclusion & exclusion criteria

Inclusion Criteria:

- Men and women, between the ages of 18 and 70 years of age;

- Body mass index from 18 to 40 kg/m2 [Body Weight (kg)/Height2 (m2)] at screening;

- Diagnosis of SLE at least 6 months before randomization, including a positive
antinuclear antibodies (ANA) during screening; if screening ANA is negative,
documented historical ANA with a titer of at least 1:80 will be acceptable;

- Any concurrent SLE pharmacologic regimen (including mycophenolate mofetil,
azathioprine, leflunomide, methotrexate, and anti-malarials) must be stable for at
least 30 days before randomization;

- Prednisone = 20 mg/day (or equivalent) is permitted; one increase or one decrease of
= 5 mg/day prednisone equivalent will be allowed within 30 days before randomization;

Additional inclusion criteria for Part B:

- Active SLE with GN with no other apparent cause, defined by the following: Renal biopsy
evidence (within 18 months) of nephritis using the WHO or International Society of
Nephrology (ISN)/Renal Pathology Society (RPS) classification of SLE with GN (Class III or
IV); Urine protein/creatinine ratio (UP/Cr) > 1 or 24 hour urine protein > 1g after at
least 12 weeks of treatment with mycophenolate mofetil (at least 1.5 grams/day) or
azathioprine (at least 100 mg orally per day); Superimposed membranous changes are allowed
for those with Class III or Class IV SLE with GN;

- Prednisone = 20 mg/day (or equivalent) at the time of randomization.

Exclusion Criteria:

- Any disorder (including psychiatric), condition or clinically significant disease
(other than a diagnosis of SLE) that would, by its progressive nature and/or
severity, interfere with the study evaluation, completion and/or procedures per the
investigator's discretion;

- Creatinine clearance within the screening period of less than 50 mL/min as calculated
by the Cockcroft-Gault method

- 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 SLE or being on allowed immunosuppressants that
predisposes one to infections

- Prior use of the following agents:

- Administration of an investigational biologic agent that primarily targets the immune
system

- Administration of cyclosporine, tacrolimus, sirolimus, IV immunoglobulin, and/or
plasmapheresis within 3 months of randomization;

- Administration of oral or IV cyclophosphamide (or any other alkylating agent) within
12 months (Part A) or 3 months (Part B) of randomization;

- History of ethanol or drug abuse within the last one year prior to randomization;

Additional exclusion criteria for Part B:

- Rapidly progressive GN (defined as a doubling of serum creatinine within the past 3
months);

- Evidence of significant chronicity, defined as:

> 50% glomeruli with sclerosis or > 50% interstitial fibrosis on renal biopsy; or
International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2003 Class III
(C), IV-S (C) or IV-G (C).



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

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Nephritis

Intervention(s)

Drug: AMG 811

Primary Outcome(s)

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 [Time Frame: 197 days]

Secondary Outcome(s)

Serum and urine PK parameters of AMG 811 [Time Frame: 197 days]

Secondary ID(s)

20070283

Source(s) of Monetary Support

Please refer to primary and secondary sponsors