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

NCT00818948 | Completed Phase 1

• 1 other identifier: 20070283
• Study Type: interventional
• Target: 56
• Locations: 5 countries
• Sites: 12

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.

Conditions

Nephritis; Systemic Lupus Erythematosus

Keywords

Lupus; Nephritis

Outcome Measures

Primary Outcomes (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

  197 days

Secondary Outcomes (1)

• Serum and urine PK parameters of AMG 811

  197 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

2 subjects of each cohort (cohort 1 to 6) will receive placebo

Drug: AMG 811

AMG811

OTHER

Six subjects in each cohort (cohort 1 to 6) will receive AMG 811

Drug: AMG 811

Interventions

AMG 811 DRUG

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; Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• \- 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.

You may not qualify if:

• 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;
• 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).

Sponsors & Collaborators

• Amgen: lead

Study Sites (12)

Research Site

Phoenix, Arizona, 85013, United States

Location

Research Site

Danbury, Connecticut, 06810, United States

Location

Research Site

Kansas City, Kansas, 66160, United States

Location

Research Site

Manhasset, New York, 11030, United States

Location

Research Site

New York, New York, 10003, United States

Location

Research Site

Duncansville, Pennsylvania, 16635, United States

Location

Research Site

Amarillo, Texas, 79106, United States

Location

Research Site

Dallas, Texas, 75231, United States

Location

Research Site

Paris, 75651, France

Location

Research Site

Hong Kong, Hong Kong

Location

Research Site

Kuala Lumpur, Kuala Lumpur, 50603, Malaysia

Location

Research Site

Mexico City, Mexico City, 14000, Mexico

Location

Related Publications (1)

• Boedigheimer MJ, Martin DA, Amoura Z, Sanchez-Guerrero J, Romero-Diaz J, Kivitz A, Aranow C, Chan TM, Chong YB, Chiu K, Wang C, Sohn W, Arnold GE, Damore MA, Welcher AA, Sullivan BA, Kotzin BL, Chung JB. Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-gamma monoclonal antibody, in SLE subjects without or with lupus nephritis. Lupus Sci Med. 2017 Sep 14;4(1):e000226. doi: 10.1136/lupus-2017-000226. eCollection 2017.

  PMID: 29018537 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Nephritis; Lupus Erythematosus, Systemic

Interventions

AMG 811

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: January 8, 2009
• Study Start: March 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 15, 2014

Record last verified: 2014-08

Locations

FR (1); MY (1); US (8); HK (1); ME (1)