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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00818948
First received: December 18, 2008
Last updated: September 11, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Nephritis
Systemic Lupus Erythematosus
Drug: AMG 811
Phase 1

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
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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serum and urine PK parameters of AMG 811 [ Time Frame: 197 days ] [ Designated as safety issue: Yes ]

Enrollment: 56
Study Start Date: March 2009
Study Completion Date: August 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00818948

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:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00818948     History of Changes
Other Study ID Numbers: 20070283
Study First Received: December 18, 2008
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Lupus
Nephritis

Additional relevant MeSH terms:
Glomerulonephritis
Lupus Erythematosus, Systemic
Nephritis
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on November 25, 2014