Systemic Lupus Erythematosus MedDRA version: 21.1 Level: LLT Classification code 10025139 Term: Lupus erythematosus systemic System Organ Class: 100000004859
Conditions
Interventions
Product Name: AMG592
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG 592
Other descriptive name: RECOMBINANT FACTOR FC FUSION PROTEIN
Concentration unit: mg/ml milligram(s)/milli
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent prior to initiation of any study specific activities/procedures. - Age = 18 years to 60 years at screening. - Fulfils diagnostic criteria for SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) criteria or by at least 4 of the 11 criteria of the 1997 American College of Rheumatology (ACR) classification criteria for SLE, with at least one of the following being present at screening: ? Antinuclear antibody 1:80; or ? Elevated anti-dsDNA antibodies - Phase 2a Subjects Only: At least one of the following at screening: ? SLEDAI 2K 6 without including anti-dsDNA or C3 and C4 complement toward the total score. If a subject qualifies for the study by scoring for arthritis on the SLEDAI 2K form, they must have 3 swollen and/or tender joints; or CLASI score 10 - Phase 2a Subjects Only: Meets SLE diagnostic and severity requirements per Central Review team at screening - Phase 2a Subjects Only: Taking at least 1 but not more than 3 of the following SLE treatments: mycophenolate mofetil, azathioprine, methotrexate, hydroxychloroquine, chloroquine, dapsone (confirmed by blood specific drug levels) or quinacrine. Subjects must be on SLE treatment for = 12 weeks and have a stable dose for 4 weeks prior to day 1. - Phase 1b Subjects only: May be taking = 3 systemic SLE treatments and the dose must be stable for = 4 weeks prior to day 1. - Prednisone dose = 20 mg daily (or other equivalent oral corticosteroid) with stable dose = 2 weeks prior to day 1 - Phase 1b Subjects Only: Normal or clinically acceptable ECG values (12-lead reporting ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline based on opinion of the investigator. - Immunizations (tetanus, diphtheria, pertussis [Td/Tdap]), seasonal influenza (during flu season), and pneumococcal (polysaccharide) vaccinations] up to date per local standards as determined by the investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: cerebritis 1 year prior to screening - Phase 2a only: Spot urine protein to creatinine ratio > 2 mg/g at screening - Diagnosis of inflammatory joint or skin disease other than SLE which would interfere with SLE disease assessment based on investigator judgement. - Diagnosis of fibromyalgia which would interfere with SLE assessment - Prosthetic joint infection within 3 years of screening or native joint infection within 1 year prior to screening. - Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1. - Known history of active tuberculosis - Positive test for tuberculosis during screening defined as either: positive purified protein derivative (PPD) (= 5 mm of induration at 48 to 2 hours after test is placed) OR positive Quantiferon test o a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test and negative chest X-ray o a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a positive or indeterminate Quantiferon test are allowed if they have ALL of the following at screening: no symptoms per tuberculosis worksheet provided by Amgen, documented history of a completed course of adequate prophylaxis (completed treatment for latent tuberculosis per local standard of care prior to the start of investigational product), no known exposure to a case of active tuberculosis after most recent prophylaxis, negative chest X-ray - Positive for hepatitis B surface antigen, hepatitis B core antibody or detectable hepatitis C virus RNA by PCR [HepCAb], followed by hepatitis C virus RNA by PCR if HepCAb is positive). A history of hepatitis B vaccination without history of hepatitis B is allowed. - Phase 1b Subjects Only: Positive for Human Immunodeficiency Virus (HIV) at screening, or known to be HIV positive Phase 2a Subjects Only: Known history of HIV - Presence of one or more significant concurrent medical conditions per investigator judgment, including but not limited to the following: poorly controlled diabetes or hypertension chronic kidney disease stage IIIb, IV, or V symptomatic heart failure myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization severe chronic pulmonary disease (eg, requiring oxygen therapy) multiple sclerosis or any other demyelinating disease major chronic inflammatory disease or connective tissue disease other than SLE (eg, RA) - Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within 5 years of screening - History of alcohol or substance abuse within 6 months of screening - Phase 1b Subjects Only: Current smoker, and/or use of any nicotine or tobacco containing products within the last 6 months prior to day 1. These types of products include but are not limited to: snuff, chewing tobacco, cigars, cigarettes, electronic cigarettes, pipes, or nicotine patches. - Phase 1b Subjects Only: Subject unwilling to limit alcohol consumption to = 1 drink of alcohol per day and 3 drinks per week for the duration of the study, where a drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits. - Currently receiving or had
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Phase 1b: • To characterize the pharmacokinetic (PK)profile following treatment with AMG 592 • To evaluate anti-AMG 592 antibody formation Phase 2a: • To evaluate the effect of treatment with AMG 592 on other measures of disease activity at various time points • To evaluate the effect of AMG 592 on tapering of corticosteroids • To evaluate the safety of AMG 592 • To evaluate anti-AMG 592 antibody formation • To characterize the PK of AMG 592 in subjects with SLE;Primary end point(s): Phase 1b • Treatment-emergent adverse events • Clinically significant changes in physical examinations, vital signs, and laboratory safety tests Phase 2a • SRI-4 response at week 24 in subjects with a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score = 6 at baseline • CLASI activity score change from baseline at week 24 in subjects with a CLASI activity score = 10 at baseline;Timepoint(s) of evaluation of this end point: Throughout study, Week 24;Main Objective: Phase 1b: To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of AMG 592 in subjects with systemic lupus erythematosus (SLE) Phase 2a: • To evaluate the efficacy of AMG 592 at week 24 as measured by the Systemic Lupus Erythematosus Responder Index (SRI-4) in subjects with moderate to severe SLE • To evaluate the efficacy of AMG 592 at week 24 as measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index score (CLASI) activity score in subjects with cutaneous SLE | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b • AMG 592 serum concentration and PK parameters including, but not limited to, maximum observed concentration (Cmax), the time of maximum observed concentration (Tmax), and area under the concentration-time curve over a dosing interval (AUCtau) after the first and last doses • Incidence of anti-AMG 592 antibodies • Cross-reactivity of anti-AMG 592 antibodies with human interleukin-2 (IL-2) • Incidence of anti-AMG 592 and anti-IL 2 neutralizing antibodies Phase 2a • SRI-4 response at week 24 in subjects with baseline SLEDAI 2K score = 6 who achieve a prednisone dose reduction to = 10 mg/day and = their baseline prednisone dose at week 16 and maintained through week 24 • SRI-4 response at week 52 in subjects with a SLEDAI 2K score = 6 at baseline • SRI-4 response at week 52 in subjects with baseline SLEDAI 2K score = 6 who achieve a prednisone dose reduction to = 10 mg/day and = their baseline prednisone dose at week 44 and maintained through week 52 • Change from baseline in SLEDAI 2K and Physician Global Asssessment (PGA) at week 24 and week 52 in subjects with a SLEDAI 2K score = 6 at baseline • CLASI activity score 50% improvement from baseline at weeks 12, 24, 36, and 52 in subjects with a CLASI activity score = 10 at baseline • CLASI activity score change from baseline at weeks 12, 36 and 52, in subjects with a CLASI activity score = 10 at baseline • Proportion of subjects at week 16 and maintained through week 24 with a prednisone dose reduction to = 7.5 mg/day and = their baseline prednisone dose • Proportion of subjects at week 44 and maintained through week 52 with a prednisone dose reduction to = 7.5 mg/day and = their baseline prednisone dose • Treatment-emergent adverse events • Clinically significant changes in vital signs, laboratory safety tests • Incidence of anti-AMG 592 antibodies • Cross-reactivity of anti-AMG 592 antibodies with IL-2 • Incidence of anti-AMG 592 and anti-IL 2 neutralizing | — |
Countries
France, Germany, Poland, United States
Contacts
Public ContactMedical Information
Amgen GmbH
Outcome results
None listed