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

• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Nephritis; Systemic Lupus Erythematosus	Drug: AMG 811	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: March 2009
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; 2 subjects of each cohort (cohort 1 to 6) will receive placebo	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.
AMG811; Six subjects in each cohort (cohort 1 to 6) will receive AMG 811	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.

Outcome Measures

Primary Outcome Measures :

1. 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 Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United States, Arizona

Research Site

Phoenix, Arizona, United States, 85013

United States, Connecticut

Research Site

Danbury, Connecticut, United States, 06810

United States, Kansas

Research Site

Kansas City, Kansas, United States, 66160

United States, New York

Research Site

Manhasset, New York, United States, 11030

Research Site

New York, New York, United States, 10003

United States, Pennsylvania

Research Site

Duncansville, Pennsylvania, United States, 16635

United States, Texas

Research Site

Amarillo, Texas, United States, 79106

Research Site

Dallas, Texas, United States, 75231

France

Research Site

Paris Cedex 13, France, 75651

Hong Kong

Research Site

Hong Kong, Hong Kong

Malaysia

Research Site

Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50603

Mexico

Research Site

Mexico, Distrito Federal, Mexico, 14000

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00818948 History of Changes
• Other Study ID Numbers: 20070283
• First Posted: January 8, 2009
• Last Update Posted: September 15, 2014
• Last Verified: August 2014

Keywords provided by Amgen:

Lupus; Nephritis

Additional relevant MeSH terms:

Nephritis; Glomerulonephritis; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Kidney Diseases; Urologic Diseases