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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04058028




Registration number
NCT04058028
Ethics application status
Date submitted
30/07/2019
Date registered
15/08/2019
Date last updated
29/10/2020

Titles & IDs
Public title
Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)
Scientific title
A Phase 2 Dose Ranging 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
Secondary ID [1] 0 0
20170588
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus (SLE) 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 570
Treatment: Drugs - Placebo for AMG 570

Experimental: AMG 570, Dose A - Investigational product solution in vial

Experimental: AMG 570, Dose B - Investigational product solution in vial

Experimental: AMG 570, Dose C - Investigational product solution in vial

Placebo Comparator: Placebo for AMG 570 - Placebo Investigational product solution in vial


Treatment: Drugs: AMG 570
AMG 570 will be presented in 5 mL glass vial

Treatment: Drugs: Placebo for AMG 570
Placebo for AMG 570 will be presented in 5 mL glass vial

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 24 - SRI-4 response at Week 24 is defined as a greater than or equal to 4-point decrease in the hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score; no new British Isles Lupus Assessment Group (BILAG) 2004 A domain score and no greater than 1 new BILAG 2004 B scores compared with baseline; and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3).
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Tender and swollen joint count = 50% improvement from baseline at week 12, 24, 36, and 52 in subjects with = 6 tender and swollen joints involving the hands and wrists at baseline - A 28-joint count will be used to evaluate the effect of AMG 570 on additional SLE efficacy endpoints. A total 28 joints will be scored for presence or absence of swelling. A separated score for joints in the hands and wrists will be calculated
Timepoint [1] 0 0
Baseline, Week 12, 24, 36, and 52
Secondary outcome [2] 0 0
Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) activity score = 50% improvement from baseline at week 12, 24, 36, and 52 in subjects with a CLASI activity score = 8 at baseline - To evaluate the effect of AMG 570 on additional SLE efficacy endpoints
Timepoint [2] 0 0
Baseline, Week 12, 24, 36, and 52
Secondary outcome [3] 0 0
Subject incidence of Treatment-Emergent Adverse Events - To characterize the safety of AMG 570
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
Subject incidence of Serious adverse events - To characterize the safety of AMG 570
Timepoint [4] 0 0
52 weeks
Secondary outcome [5] 0 0
Number of Subjects with significant changes in laboratory values - To characterize the safety of AMG 570
Timepoint [5] 0 0
52 weeks
Secondary outcome [6] 0 0
Number of Subjects with significant changes in vital signs - To characterize the safety of AMG 570
Timepoint [6] 0 0
52 weeks
Secondary outcome [7] 0 0
Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS-Fatigue SF7A) score change from baseline - To describe the effect of treatment with AMG 570 using patient reported outcomes
Timepoint [7] 0 0
Baseline, Week 12, 24, 36, 44 and 52
Secondary outcome [8] 0 0
Medical Outcomes Short Form 36 version 2 Questionnaire (SF36v2) score change from baseline - To describe the effect of treatment with AMG 570 using patient reported outcomes
Timepoint [8] 0 0
Baseline, Week 12, 24, 36, 44 and 52
Secondary outcome [9] 0 0
Modified Lupus Quality of Life (QoL) score and change from baseline - To describe the effect of treatment with AMG 570 using patient reported outcomes
Timepoint [9] 0 0
Baseline, Week 12, 24, 36, 44 and 52
Secondary outcome [10] 0 0
Patient Global Assessment (PtGA) score change from baseline - This is an 11-point NRS with 0 indicating lowest disease and 10 highest disease activity.
Timepoint [10] 0 0
Baseline, Week 12, 24, 36, 44 and 52
Secondary outcome [11] 0 0
Serum AMG 570 trough concentrations - To characterize the pharmacokinetics (PK) of AMG 570
Timepoint [11] 0 0
52 Weeks
Secondary outcome [12] 0 0
AMG 570 terminal elimination half-life, if possible - To characterize the pharmacokinetics (PK) of AMG 570
Timepoint [12] 0 0
52 weeks
Secondary outcome [13] 0 0
SRI-4 at week 52 with reduction of OCS to less than or equal to 7.5 mg/day by week 44 and sustained through week 52 in subjects with a baseline OCS dose = 10 mg/day - To evaluate the efficacy of AMG 570 with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.
Timepoint [13] 0 0
week 52
Secondary outcome [14] 0 0
Percent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 52 - SRI-4 response at Week 52 is defined as a greater than or equal to 4-point decrease in the hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score; no new British Isles Lupus Assessment Group (BILAG) 2004 A domain score and no greater than 1 new BILAG 2004 B scores compared with baseline; and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3).
Timepoint [14] 0 0
Week 52
Secondary outcome [15] 0 0
Percent of patients achieving Lupus Low Disease Activity State (LLDAS) at week 52 - LLDAS response at week 52 is defined as a hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score = 4 with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, and fever) and no haemolytic anaemia or gastrointestinal activity; no new findings of lupus disease activity compared with the previous assessment; = 1-point in Physician Global Assessment (PGA) (scale 0 to 3) current prednisolone-equivalent dosage = 7.5 mg/day; and standard maintenance dosages of immunosuppressive drugs and approved biologics.
Timepoint [15] 0 0
Week 52
Secondary outcome [16] 0 0
Percent on patients achieving The British Isles Lupus Assessment Group (BILAG) based Combined Lupus Assessment (BICLA) index responses - BICLA response is defined as at least 1 gradation of improvement in baseline BILAG domain scores in all body systems with moderate or severe disease activity at entry (eg, all A [severe disease] domain scores falling to B [moderate], C [mild], or D [no activity], and all B domain scores falling to C or D); no new BILAG 2004 A domain score and no greater than 1 new BILAG 2004 B domain scores compared with baseline; less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3); and no initiation of non-protocol treatment.
Timepoint [16] 0 0
Week 24 and Week 52

Eligibility
Key inclusion criteria
Inclusion Criteria Screening Visit:

- 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.

- Anti-dsDNA results based on the Farr assay will be used to SLE classification
criteria, while test results from the Phadia method will be used for the purposes of
hSLEDAI scoring during screening and throughout the study.

- 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 must involve joints in the hands or wrists, and for the hSLEDAI
score the distribution should not involve the ankles, knees, hips, elbows, or
shoulders

- 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 must be documented by an ophthalmologist and other causes excluded.

- Renal: subjects with urine protein/creatinine ratio < 3000 mg/g (or equivalent) 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.

- 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. If
subject is taking 2 of the above mentioned SLE treatments, 1 of these must be
either hydroxychloroquine, quinacrine, or chloroquine.

- 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.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria Screening Visit

Subjects are excluded from the study if any of the following criteria apply:

Disease Related

- History of lupus nephritis requiring induction therapy within 1 year or active lupus
nephritis defined as urine protein creatinine ratio = 3000 mg/g (or equivalent) at
screening.

- History of 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Research Site - Sydney
Recruitment hospital [2] 0 0
Research Site - Woodville South
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Oklahoma
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Argentina
State/province [10] 0 0
Tucuman
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Plovdiv
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Sofia
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha 2
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux
Country [17] 0 0
France
State/province [17] 0 0
Caen Cedex 9
Country [18] 0 0
France
State/province [18] 0 0
Lille cedex 01
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Strasbourg
Country [21] 0 0
France
State/province [21] 0 0
Toulouse
Country [22] 0 0
Germany
State/province [22] 0 0
Leipzig
Country [23] 0 0
Hungary
State/province [23] 0 0
Debrecen
Country [24] 0 0
Hungary
State/province [24] 0 0
Gyula
Country [25] 0 0
Italy
State/province [25] 0 0
Milano
Country [26] 0 0
Italy
State/province [26] 0 0
Pisa
Country [27] 0 0
Italy
State/province [27] 0 0
Roma
Country [28] 0 0
Italy
State/province [28] 0 0
Rozzano MI
Country [29] 0 0
Japan
State/province [29] 0 0
Chiba
Country [30] 0 0
Japan
State/province [30] 0 0
Fukuoka
Country [31] 0 0
Japan
State/province [31] 0 0
Hokkaido
Country [32] 0 0
Japan
State/province [32] 0 0
Miyagi
Country [33] 0 0
Japan
State/province [33] 0 0
Nagasaki
Country [34] 0 0
Japan
State/province [34] 0 0
Okayama
Country [35] 0 0
Japan
State/province [35] 0 0
Shizuoka
Country [36] 0 0
Japan
State/province [36] 0 0
Tokyo
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Suwon-si, Gyeonggi-do
Country [39] 0 0
Mexico
State/province [39] 0 0
Baja California Norte
Country [40] 0 0
Mexico
State/province [40] 0 0
Guanajuato
Country [41] 0 0
Mexico
State/province [41] 0 0
Jalisco
Country [42] 0 0
Mexico
State/province [42] 0 0
Yucatán
Country [43] 0 0
Poland
State/province [43] 0 0
Katowice
Country [44] 0 0
Poland
State/province [44] 0 0
Krakow
Country [45] 0 0
Poland
State/province [45] 0 0
Lublin
Country [46] 0 0
Poland
State/province [46] 0 0
Stalowa Wola
Country [47] 0 0
Poland
State/province [47] 0 0
Wroclaw
Country [48] 0 0
Portugal
State/province [48] 0 0
Lisboa
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Kemerovo

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine if AMG 570 could be a useful therapeutic agent in
the current treatment landscape where subjects with systemic lupus erythematosus (SLE) have
ongoing disease activity despite treatment with standard of care therapies.
Trial website
https://clinicaltrials.gov/show/NCT04058028
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04058028