Safety and Efficacy of AMG 592 in Subjects With Active Systemic Lupus Erythematosus

Phase 1

• Conditions: Systemic Lupus Erythematosus; Therapeutic area: Body processes [G] - Immune system processes [G12]; MedDRA version: 21.1Level: LLTClassification code 10025139Term: Lupus erythematosus systemicSystem Organ Class: 100000004859

• Registration Number: EUCTR2017-002564-40-DE
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-12-04
• Last Update Posted: 29 April 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 140

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified