Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)

JRCT ID: jRCT2080225306

Registered date:11/08/2020

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: Systemic Lupus Erythematosus (SLE)
• Date of first enrollment: 19/02/2020
• Target sample size: 320
• Countries of recruitment: United States,Argentina,Australia,Bulgaria,Canada,Czechia,France,Germany,Greece,Hong Kong,Hungary,Italy,Korea,Mexico,Poland,Portugal,Russian Federation,Spain
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : Rozibafusp Alfa
INN of investigational material : Rozibafusp Alfa
Therapeutic category code : 339 Other agents relating to blood and body fluids
Dosage and Administration for Investigational material : Rozibafusp Alfa 70 mg, 280 mg, or 420 mg will be administered subcutaneously every 2 weeks

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Placebo will be administered subcutaneously once every 2 weeks.

Outcome(s)

Primary Outcome

Efficacy
1. Percent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 52 [ Time Frame: 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, and no new British Isles Lupus Assessment Group (BILAG) 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3), and no use of more than protocol allowed therapies.

Secondary Outcome

safety
efficacy
exploratory
pharmacokinetics
1. Percent of patients achieving a SRI-4 response at week 24 [ Time Frame: 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, and no new British Isles Lupus Assessment Group (BILAG) 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3), and no use of more than protocol allowed therapies.
2. Percent of patients achieving Lupus Low Disease Activity State (LLDAS) at week 52 [ Time Frame: 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.
3. Percent of patients achieving The British Isles Lupus Assessment Group (BILAG) based Combined Lupus Assessment (BICLA) index responses [ Time Frame: Week 24 and Week 52 ]
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 >than 1 new BILAG 2004 B domain scores compared with baseline; no worsening of the hSLEDAI score from baseline; no >= 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3); and no use of more than protocol-allowed therapies; and no initiation of non-protocol treatment for SLE.
4. 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 [ Time Frame: week 52 ]
To evaluate the efficacy of Rozibafusp Alfa with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.
5. Annualized moderate and severe flare rate [ Time Frame: 52 weeks ]
Measured by SELENA-SLEDAI Flare Index.
6. Annualized severe flare rate [ Time Frame: 52 weeks ]
Measured by SELENA-SLEDAI Flare Index.
7. Annualized flare rate [ Time Frame: 52 weeks ]
Measured by BILAG score designation of "worse" or "new" resulting in a B score in >= 2 organs or an A score in >= 1 organ) over 52 weeks.
8. Total tender and swollen joint count (limited to hands and wrists): >= 50% improvement from baseline at week 12, 24, 36, and 52 in subjects with >= 6 tender and swollen joints in the hands and wrists at baseline [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
A joint count will be used to evaluate the effect of Rozibafusp Alfa on additional SLE efficacy endpoints.
9. 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 [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To evaluate the effect of Rozibafusp Alfa on additional SLE efficacy endpoints
10. Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS-Fatigue SF7A) score change from baseline [ Time Frame: Baseline, Week 12, 24, 36, 44 and 52 ]
To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes
11. Medical Outcomes Short Form 36 version 2 Questionnaire (SF-36v2) physical component score change from baseline [ Time Frame: Baseline, Week 12, 24, 36, 44 and 52 ]
To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes
12. Medical Outcomes Short Form 36 version 2 Questionnaire (SF-36v2) mental component score individual domains change from baseline [ Time Frame: Baseline, Week 12, 24, 36, 44 and 52 ]
To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes
13. Lupus Quality of Life (QoL) score and change from baseline [ Time Frame: Baseline, Week 12, 24, 36, 44 and 52 ]
To describe the effect of treatment with Rozibafusp Alfa using patient reported outcomes
14. Patient Global Assessment (PtGA) score change from baseline [ Time Frame: Baseline, Week 12, 24, 36, 44 and 52 ]
This is an 11-point NRS with 0 indicating lowest disease and 10 highest disease activity.
15. Patient incidence of Treatment-Emergent Adverse Events [ Time Frame: 52 weeks ]
To characterize the safety of Rozibafusp Alfa
16. Patient incidence of Serious adverse events [ Time Frame: 52 weeks ]
To characterize the safety of Rozibafusp Alfa
17. Number of patients with significant changes in laboratory values [ Time Frame: 52 weeks ]
To characterize the safety of Rozibafusp Alfa
18. Number of patients with significant changes in vital signs [ Time Frame: 52 weeks ]
To characterize the safety of Rozibafusp Alfa
19. Serum Rozibafusp Alfa trough concentrations [ Time Frame: 52 Weeks ]
To characterize the pharmacokinetics (PK) of Rozibafusp Alfa
20. Rozibafusp Alfa terminal elimination half-life, if possible [ Time Frame: 52 weeks ]
To characterize the pharmacokinetics (PK) of Rozibafusp Alfa

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

Inclusion Criteria Screening Visit:
1. Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
2. Age >= 18 years to <= 75 years at screening visit.
3. 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.
4. 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 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.
5. 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.
6. 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.

Exclude criteria

Exclusion Criteria Screening Visit
Subjects are excluded from the study if any of the following criteria apply:
Disease Related:
1. Urine protein creatinine ratio >= 3000 mg/g (or equivalent) at screening or induction therapy for lupus nephritis within 1 year prior to screening visit.
2. 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.

Related Information

• Primary Sponsor: Amgen K.K.
• Secondary ID(s): NCT04058028,JapicCTI-205402