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

Systemic Lupus Erythematosus Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00818948
• Other study ID #: 20070283
• Status: Completed
• Phase: Phase 1
• First received: December 18, 2008
• Last updated: September 11, 2014
• Start date: March 2009
• Est. completion date: August 2014

Study information

• Verified date: August 2014
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a 2-part, multi-center, randomized, double-blind, placebo-controlled, multiple dose escalation study, enrolling approximately 48 subjects. Part A of the study will enroll subjects with Systemic Lupus Erythematosus (SLE) without Glomerulonephritis (GN) into 3 cohorts. Part B of the study will enroll SLE subjects with GN into 3 cohorts. The purpose of the study is to evaluate the multiple dose of AMG 811 on safety. Tolerability and pharmacokinetics.

Description:

Part A of the study will enroll SLE without GN (non-renal) subjects into 3 cohorts (6 AMG 811: 2 placebo). All subjects will receive a dose of AMG 811 or placebo every 4 weeks beginning with Day 1 (D1) for a total of 3 injections. Subjects will be followed through to study day 197, 5 months from the last dose of study medication.

Part B of the study will enroll SLE subjects with GN into Cohorts 4, 5, and 6 (6 AMG 811: 2 placebo). Similar to Part A, subjects in Cohorts 4, 5, and 6 will be dosed every 4 weeks with AMG 811 or placebo for a total of 3 injections followed by a 5 month follow-up period. For Cohort 6, subjects will be followed by a 6 month follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: August 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glomerulonephritis
• Lupus Erythematosus, Systemic
• Nephritis
• Systemic Lupus Erythematosus

Intervention

Drug:
• AMG 811
Part A of the study will enroll SLE without GN (non-renal) subjects into 3 cohorts (6 AMG 811: 2 placebo). All subjects will receive a dose of AMG 811 or placebo every 4 weeks beginning with day 1 (D1) for a total of 3 injections. Subjects will be followed through to study day 197, 5 months from the last dose of study medication. Part B of the study will enroll SLE subjects with GN into Cohorts 4, 5 and 6 (6 AMG 811: 2 placebo). Similar to Part A, subjects in Cohorts 4, 5 and 6 will be dosed every 4 weeks with AMG 811 or placebo for a total of 3 injections followed by a 5 month follow-up period. For Cohort 6, subjects will be followed by a 6 month follow-up period.

Locations

Country	Name	City	State
France	Research Site	Paris Cedex 13
Hong Kong	Research Site	Hong Kong
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Mexico	Research Site	Mexico	Distrito Federal
United States	Research Site	Amarillo	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Danbury	Connecticut
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Kansas City	Kansas
United States	Research Site	Manhasset	New York
United States	Research Site	New York	New York
United States	Research Site	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		197 days	Yes
Secondary	Serum and urine PK parameters of AMG 811		197 days	Yes

External Links

•   AmgenTrials clinical trials website