A Study to Evaluate the Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE) With Inadequate Response to Standard of Care (SOC) Therapy
- Conditions
- Active Systemic Lupus ErythematosusMedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-000328-16-FR
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 300
- Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
- Age ? 18 years to ? 75 years at visit 1.
- Fulfills classification criteria for SLE according to the SLICC criteria or by at least 4 of the 11 criteria of the 1997 modification of the ACR classification criteria for SLE, with at least 1 of the following being present at screening: Antinuclear antibody ? 1:80; or Elevated anti-dsDNA antibodies by the Farr assay.
- SLEDAI-2K score ? 6 points with Clinical SLEDAI-2K score ? 4 points. The Clinical SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures. For a subject whose clinical SLEDAI-2K score requires any of the following components, the subject must meet the following additional criteria:
o Arthritis: 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 in the hands or wrists, and the distribution should not involve the ankles, elbows, shoulders, or hips.
o Alopecia: Subjects scoring for alopecia on the SLEDAI-2K should have patchy hair loss without scarring; subjects should neither have alopecia areata nor androgenic alopecia.
o Oral ulcers: Subjects scoring for oral ulcers on the SLEDAI-2K should have physician documented location and appearance.
o Rash: To contribute to the minimally required clinical SLEDAI-2K score, rash must have been present for a minimum of 1 week, must cover at least 5% of the body surface area if discoid and 10% of the body surface area if any other type of lupus rash. Rash must have physician documented location and appearance.
- Must be taking at least 1 but not more than 2 of the following SLE treatments: mycophenolate mofetil, azathioprine, methotrexate, hydroxychloroquine, chloroquine, dapsone, or quinacrine. Treatment should be taken for ?12 weeks prior to screening and must be a stable dose for ? 8 weeks prior to screening. Patients cannot be taking two immunosuppresants (ie, mycophenolate mofetil, azathioprine, or methotrexate) simultaneously.
- For subjects taking OCS, dose must be ? 20 mg/day of prednisone or OCS equivalent, and the dose must be stable ? 4 weeks prior to screening.
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 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
- History of lupus nephritis requiring induction therapy within 1 year or active lupus nephritis (defined as any of the following: clean catch, spot urine protein creatinine ratio > 3000 mg/g at screening or active urinary sediment attributable to SLE).
- History of CNS lupus within 1 year prior to screening or active CNS lupus including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.
- Currently present or within 1 year prior to screening a diagnosis of any inflammatory joint or skin disease other than SLE (confirmed accurate by the PI) which would interfere with SLE disease assessment based on investigator judgement.
- History of any disease other than SLE that has required treatment with oral or parenteral corticosteroids for > 2 weeks within 6 months 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 or indeterminate QuantiFERON®-TB or T-spot test OR positive purified protein derivative (PPD) (? 5 mm of induration at 48 to 72 hours after test is placed).
- Positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B DNA polymerase chain reaction [PCR] test) or detectable hepatitis C virus RNA by PCR (screening is generally done by hepatitis C antibody [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.
- Known history of HIV or positive serology for HIV antibodies at screening.
- Presence of 1 or more significant concurrent medical conditions per investigator judgment, including but not limited to the following:
o poorly controlled diabetes or hypertension (ie, systolic blood pressure > 170 mmHg and/or diastolic blood pressure > 100 mmHg)
o symptomatic heart failure (New York Heart Association class III or IV)
o myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization
o severe chronic pulmonary disease (eg, requiring oxygen therapy)
o multiple sclerosis or any other demyelinating disease
o major chronic inflammatory disease or connective tissue disease other than SLE (eg, RA, mixed connective tissue disease [MCTD], antiphospholipid antibody syndrome)
- Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent ? 6 months prior to day 1 OR oral calcineurin inhibitors (eg, cyclosporine, tacrolimus, sirolimus, voclosporin) ? 4 weeks prior to day 1.
- Currently receiving or had treatment with a JAK inhibitor or oral, targeted investigational agent (eg, Bruton’s tyrosine kinase inhibitor) < 3 months or 5 half-lives (whichever is longer) prior to day 1.
- Prior treatment with an immune checkpoint inhibitor (eg, PD-1 i
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of AMG 570 at week 24 as measured by the Systemic Lupus Erythematosus Responder Index (SRI-4) in subjects with SLE with inadequate response to SOC therapy;<br> Secondary Objective: - To evaluate the efficacy of AMG 570 with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy (key secondary). <br> - To evaluate the effect of AMG 570 on the efficacy response after 52 weeks of treatment (key secondary).<br> - To evaluate the effect of AMG 570 on additional SLE efficacy endpoints.<br> - To describe the effect of treatment with AMG 570 using patient reported outcome.<br> - To characterize the safety of AMG 570.<br> - To characterize the pharmacokinetics (PK) of AMG 570.<br> ;Primary end point(s): - SRI-4 response at week 24.;Timepoint(s) of evaluation of this end point: - Week 24
- Secondary Outcome Measures
Name Time Method