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

• ClinicalTrials.gov Identifier: NCT04058028
• Recruitment Status: Active, not recruiting
• First Posted: August 15, 2019
• Last Update Posted: March 9, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: July 30, 2019
• First Posted Date: August 15, 2019
• Last Update Posted Date: March 9, 2023
• Actual Study Start Date: February 19, 2020
• Estimated Primary Completion Date: July 11, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 14, 2022)

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.

Original Primary Outcome Measures (submitted: August 13, 2019)

Per cent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 24. [ Time Frame: Week 24 ]

The SRI-4 is a composite endpoint that requires a greater than or equal to 4-point decrease in the SLE Disease Activity Index 2000 (SLEDAI-2K), an absence of worsening in the British Isles Lupus Assessment Group (BILAG) instrument, and an absence of worsening in the Physician's Global Assessment of Disease Activity.

Current Secondary Outcome Measures (submitted: September 14, 2022)

• 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.
• 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.
• 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.
• 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.
• Annualized moderate and severe flare rate [ Time Frame: 52 weeks ]
  Measured by SELENA-SLEDAI Flare Index.
• Annualized severe flare rate [ Time Frame: 52 weeks ]
  Measured by SELENA-SLEDAI Flare Index.
• 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.
• 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.
• 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
• 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
• 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
• 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
• 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
• 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.
• Patient incidence of Treatment-Emergent Adverse Events [ Time Frame: 52 weeks ]
  To characterize the safety of Rozibafusp Alfa.
• Patient incidence of Serious adverse events [ Time Frame: 52 weeks ]
  To characterize the safety of Rozibafusp Alfa.
• Number of patients with significant changes in laboratory values [ Time Frame: 52 weeks ]
  To characterize the safety of Rozibafusp Alfa.
• Number of patients with significant changes in vital signs [ Time Frame: 52 weeks ]
  To characterize the safety of Rozibafusp Alfa.
• Serum Rozibafusp Alfa trough concentrations [ Time Frame: 52 Weeks ]
  To characterize the pharmacokinetics (PK) of Rozibafusp Alfa
• Rozibafusp Alfa terminal elimination half-life, if possible [ Time Frame: 52 weeks ]
  To characterize the pharmacokinetics (PK) of Rozibafusp Alfa

Original Secondary Outcome Measures (submitted: August 13, 2019)

• Per cent of patients with an improvement in tender and swollen join count greater than or equal to 50% amongst those with greater than or equal to 6 tender and greater than or equal to 6 swollen joints at baseline [ Time Frame: Week 12, 24, 36, 52 ]
  A 28-joint count will be used to evaluate the effect of AMG 570 on additional SLE efficacy endpoints.
• Per cent of patients who achieve a greater than or equal to 50% improvement from baseline in the Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) activity score amongst those with a CLASI score greater than or equal to 10 at baseline. [ Time Frame: Week 12, 24, 36, 52 ]
  To evaluate the effect of AMG 570 on additional SLE efficacy endpoints
• Subject incidence of Adverse Events [ Time Frame: 52 weeks ]
  To characterize the safety of AMG 570
• Subject incidence of Serious adverse events [ Time Frame: 52 weeks ]
  To characterize the safety of AMG 570
• Number of Subjects with significant changes in laboratory values [ Time Frame: 52 weeks ]
  To characterize the safety of AMG 570
• Number of Subjects with significant changes in vital signs [ Time Frame: 52 weeks ]
  To characterize the safety of AMG 570
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
  To describe the effect of treatment with AMG 570 using patient reported outcomes
• Medical Outcomes Short Form 36 version 2 Questionnaire (SF36v2) score change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
  To describe the effect of treatment with AMG 570 using patient reported outcomes
• Modified Lupus QoL score and change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
  To describe the effect of treatment with AMG 570 using patient reported outcomes
• Patient Global Assessment (PtGA) score change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
  This is an 11-point NRS with 0 indicating lowest disease and 10 highest disease activity.
• Serum AMG 570 trough concentrations [ Time Frame: 52 Weeks ]
  To characterize the pharmacokinetics (PK) of AMG 570
• AMG 570 terminal elimination half-life, if possible [ Time Frame: 52 weeks ]
  To characterize the pharmacokinetics (PK) of AMG 570
• 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 [ Time Frame: week 52 ]
  To evaluate the efficacy of AMG 570 with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.
• Per cent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 52 [ Time Frame: Week 52 ]
  The SRI-4 is a composite endpoint that requires a greater than or equal to 4-point decrease in the SLE Disease Activity Index 2000 (SLEDAI-2K), an absence of worsening in the British Isles Lupus Assessment Group (BILAG) instrument, and an absence of worsening in the Physician's Global Assessment of Disease Activity.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)
• Official Title: A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Rozibafusp Alfa (AMG 570) in Subjects With Active Systemic Lupus Erythematosus (SLE) With Inadequate Response to Standard of Care (SOC) Therapy
• Brief Summary: The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ongoing disease activity despite treatment with standard of care therapies.
• Detailed Description: This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including oral corticosteroids (OCS), immunosuppressants and immunomodulators. Previous biologic use is allowed with an adequate washout period.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including OCS, immunosuppressants, and immunomodulators. Subjects will be randomized to receive placebo or 1 of 3 doses of Rozibafusp Alfa with the last dose at week 50. Treatment will be administered every 2 weeks (Q2W). All subjects will be required to complete a 16-week follow-up period after the 52-week treatment period.

The first interim analysis (IA) will be executed after the first 40 enrolled subjects have had the opportunity to complete the week 24 assessment. Additional IAs may be executed after approximately every 32 newly enrolled subjects have had the opportunity to complete the week 24 assessment. The last IA will occur when all subjects have had the opportunity to complete the week 24 assessment.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Systemic Lupus Erythematosus (SLE)

Intervention

• Drug: Rozibafusp Alfa
  Rozibafusp Alfa will be presented in 5 mL glass vial
• Drug: Placebo for Rozibafusp Alfa
  Placebo for Rozibafusp Alfa will be presented in 5 mL glass vial

Study Arms

• Experimental: Rozibafusp Alfa, Dose A
  Investigational product solution in vial
  Intervention: Drug: Rozibafusp Alfa
• Experimental: Rozibafusp Alfa, Dose B
  Investigational product solution in vial
  Intervention: Drug: Rozibafusp Alfa
• Experimental: Rozibafusp Alfa, Dose C
  Investigational product solution in vial
  Intervention: Drug: Rozibafusp Alfa
• Placebo Comparator: Placebo for Rozibafusp Alfa
  Placebo Investigational product solution in vial
  Intervention: Drug: Placebo for Rozibafusp Alfa

• Publications *: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 22, 2021): 320
• Original Estimated Enrollment (submitted: August 13, 2019): 300
• Estimated Study Completion Date: July 11, 2023
• Estimated Primary Completion Date: July 11, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.
• 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.

• 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.

Exclusion Criteria Screening Visit

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

Disease Related

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Bulgaria, Canada, Czechia, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Russian Federation, Spain, United States

Administrative Information

• NCT Number: NCT04058028
• Other Study ID Numbers: 20170588
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• URL: http://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: March 2023