Safety and Efficacy of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)
- Conditions
- Active Systemic Lupus Erythematosus (SLE)MedDRA version: 21.1Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-000328-16-GR
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 320
- Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
- Age = 18 years to = 75 years at screening visit .
- Fulfills classification criteria for SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE (Aringer et al, 2019), with antinuclear antibody = 1:80 by immunofluorescence on Hep-2 cells being present at screening.
- Hybrid SLEDAI score = 6 points with a Clinical hSLEDAI score = 4 points. The Clinical hSLEDAI is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results, including urine or immunologic parameters.
Additional protocol-specific rules are applied at screening and throughout the study, as follows:
- Arthritis: Arthritis (at least 3 tender and swollen joints) must involve joints in the hands or wrists for the hSLEDAI scoring.
- Alopecia: Subjects should have hair loss without scarring; should neither have alopecia areata nor androgenic alopecia; and should have a CLASI activity score for alopecia = 2.
- Oral ulcers: Ulcers location and appearance must be documented by the investigator.
- Scleritis and Episcleritis: the presence of stable SLE-related scleritis and episcleritis (ie, that will likely not require initiation/increase in immunosuppressants/immunomodulators as outlined in the inclusion/exclusion criteria) must be documented by an ophthalmologist and other causes excluded.
- Renal: subjects with urine protein/creatinine ratio < 3000 mg/g (or equivalent method) in a clear catch spot urine sample can enroll and be scored in the hSLEDAI, provided the subject has a clinical hSLEDAI = 4 and did not receive induction treatment for nephritis within the last year.
- Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be accompanied by objective findings to be scored in the hSLEDAI.
- Unless there is a documented intolerance, subjects must be taking:
•Only 1 of the following SLE treatments: anti malarial
(hydroxychloroquine, chloroquine, or quinacrine), azathioprine,
methotrexate, leflunomide, mycophenolate mofetil/acid mycophenolic,
or dapsone.
OR
•2 of the above-mentioned SLE treatments in which 1 must be anti
malarial (hydroxychloroquine, chloroquine, or quinacrine).
Treatment should be taken for = 12 weeks prior to screening and must be a stable dose for = 8 weeks prior to screening.
- For subjects taking OCS, dose must be = 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit for = 2 weeks prior to screening visit
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 295
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
- Urine protein creatinine ratio = 3000 mg/g (or equivalent) at screening or induction therapy for lupus nephritis within 1 year prior to screening visit.
- Active CNS lupus within 1 year prior to screening including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.
- Diagnosis of any inflammatory joint or skin disease other than SLE (confirmed accurate by the PI) currently present or within 1 year prior to screening which would interfere with SLE disease assessment based on investigator judgment.
- Any disease other than SLE that has required treatment with oral or parenteral CS for > 2 weeks within 6 weeks prior to screening.
- Active infection OR infection for which anti-infectives were initiated within 4 weeks prior to screening OR presence of serious infection, defined as requiring hospitalization or IV anti-infectives within 8 weeks prior to screening.
- Active tuberculosis or latent tuberculosis with no documented past history of adequate treatment per local standard of care.
- Positive test for tuberculosis during screening defined as either positive or indeterminate QuantiFERON®-TB or T-spot test OR positive purified protein derivative (PPD).(see details in protocol).
- Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb) in the presence of detectable viral DNA in peripheral blood. (see exception details in protocol).
- Positive for hepatitis C antibody in the presence of detectable viral ribonucleic acid (RNA) in peripheral blood, assessed by PCR. (see exception details in protocol).
- Known history of HIV or positive serology for HIV antibodies at screening.
- Presence of 1 or more significant concurrent medical conditions per investigator judgment (see details in protocol).
- Any history of malignancy with the following exceptions:
•resolved non-melanoma skin cancers > 5 years prior to screening
•resolved cervical carcinoma > 5 years prior to screening
•resolved malignant colon polyps > 5 years prior to screening
- Currently receiving or had treatment with: cyclophosphamide,
chlorambucil, nitrogen mustard, or any other alkylating agent within 6 months prior to screening; sirolimus or oral calcineurin inhibitors or
thalidomide within 4 weeks prior screening.
- Currently receiving or had treatment with a Janus Kinase (JAK)
inhibitor within 1month prior to screening.
- Currently receiving or had treatment with an immune checkpoint inhibitor.
- Current or previous treatment with a biologic agent with
immunosuppressive/immunomodulatory activity for SLE or other
conditions as follows: rituximab within 6 months prior to screening;
abatacept, belimumab, and anifrolumab within the past 3 months prior to screening; other biologics within less than 5 drug half-lives or within the period of pharmacodynamic activity, when relevant, prior to screening.
- Subjects who have received intra-articular, intra-lesional, or systemic corticosteroid injections within 6 weeks prior to screening.
-Subjects who have received live vaccines within 5 weeks prior to screening, or plan to receive live vaccines during the treatment period and up to 16 weeks after the last administration of the investigational product.
- Currently receiving treatment in another investigational device or drug study.
- Ending a treatment with an investigational drug or investigational
device less than 5 drug h
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the efficacy of AMG 570 at week 52 as measured by the Systemic Lupus Erythematosus Responder Index (SRI-4);Secondary Objective: - Evaluate the efficacy of AMG 570 at week 24 <br>- Evaluate the efficacy of AMG 570 at week 52<br>- Evaluate the efficacy of AMG 570 as measured by SRI-4 response with oral corticosteroid (OCS) tapering <br>- Evaluate the efficacy of AMG 570 on disease flares<br>- Evaluate the efficacy of AMG 570 on joints and skin<br>- Describe the efficacy of AMG 570 using patient reported outcomes<br>- 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 52;Timepoint(s) of evaluation of this end point: - Week 52
- Secondary Outcome Measures
Name Time Method