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
Overview
- Phase
- Phase 1
- Intervention
- AMG 811
- Conditions
- Nephritis
- Sponsor
- Amgen
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
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.
Investigators
Eligibility 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:
Arms & Interventions
Placebo
2 subjects of each cohort (cohort 1 to 6) will receive placebo
Intervention: AMG 811
AMG811
Six subjects in each cohort (cohort 1 to 6) will receive AMG 811
Intervention: AMG 811
Outcomes
Primary Outcomes
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 Outcomes
- Serum and urine PK parameters of AMG 811(197 days)