December 18, 2020
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December 23, 2020
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October 4, 2023
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May 6, 2021
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May 22, 2023 (Final data collection date for primary outcome measure)
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Percent of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 52 [ Time Frame: Week 52 ] SRI-4 response 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 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) VAS (scale 0 to 3).
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Same as current
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- Percent of Participants Achieving a British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 24 and Week 52 [ Time Frame: Week 24 and Week 52 ]
BICLA response is defined as at least 1 gradation of improvement in baseline British Isles Lupus Assessment Group (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.
- Percent of Participants Achieving a Lupus Low Disease Activity State (LLDAS) Response at Week 52 [ Time Frame: Week 52 ]
LLDAS response 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 Participants with a Reduction of Oral Corticosteroid (OCS) to Less Than or Equal to 7.5 mg/day by Week 44 and Sustained Through Week 52 in Participants with a Baseline OCS Dose ≥ 10 mg/day [ Time Frame: Week 52 ]
To evaluate the efficacy of efavaleukin alfa with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.
- Percent of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 [ Time Frame: Week 24 ]
SRI-4 response 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).
- Percent of Participants Achieving a Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) Response at Week 24 and Week 52 [ Time Frame: Week 24 and Week 52 ]
hSLEDAI response is defined as a greater than or equal to 4-point decrease in score.
- Tender and Swollen Joint Count ≥ 50% Improvement from Baseline at Weeks 8, 12, 24, 36, and 52 in Participants with ≥ 6 Tender and Swollen Joints Involving the Hands and Wrists at Baseline [ Time Frame: Baseline, Week 8, 12, 24, 36, and 52 ]
A 28-joint count will be used to evaluate the effect of efavaleukin alfa 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.
- Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score ≥ 50% Improvement from Baseline at Week 8, 12, 24, 36, and 52 in Participants with a CLASI Activity Score ≥ 8 at Baseline [ Time Frame: Baseline, Week 8, 12, 24, 36, and 52 ]
To evaluate the effect of efavaleukin alfa on additional SLE efficacy endpoints.
- Percent of Participants who Experience a Flare [ Time Frame: Week 52 ]
A flare is defined as a British Isles Lupus Assessment Group (BILAG) score designation of 'worse' or 'new'.
- Change from Baseline in Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS Fatigue SF 7A) Fatigue Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes.
- Change from Baseline in Medical Outcomes Short Form-36 Questionnaire Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes.
- Change from Baseline in Lupus Quality of Life (QoL) Questionnaire Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes.
- Number of Participants who Experience a Treatment-Emergent Adverse Event (AE) and Serious Adverse Event (SAE) [ Time Frame: Up to Week 56 ]
To characterize the safety of efavaleukin alfa.
- Number of Participants who Experience a Clinically Significant Change in Laboratory Values and Vital Sign Measurements [ Time Frame: Up to Week 56 ]
To characterize the safety of efavaleukin alfa.
- Trough Serum and Sparse Postdose Serum Concentration of Efavaleukin Alfa [ Time Frame: Up to Week 52 ]
To characterize the pharmacokinetics (PK) of efavaleukin alfa.
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- Percent of Participants Achieving a British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 24 and Week 52 [ Time Frame: Week 24 and Week 52 ]
BICLA response is defined as at least 1 gradation of improvement in baseline British Isles Lupus Assessment Group (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.
- Percent of Participants Achieving a Lupus Low Disease Activity State (LLDAS) Response at Week 52 [ Time Frame: Week 52 ]
LLDAS response 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 Participants with a Reduction of Oral Corticosteroid (OCS) to Less Than or Equal to 7.5 mg/day by Week 44 and Sustained Through Week 52 in Participants with a Baseline OCS Dose ≥ 10 mg/day [ Time Frame: Week 52 ]
To evaluate the efficacy of efavaleukin alfa with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.
- Percent of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 [ Time Frame: Week 24 ]
SRI-4 response 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).
- Percent of Participants Achieving a Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) Response at Week 24 and Week 52 [ Time Frame: Week 24 and Week 52 ]
hSLEDAI response is defined as a greater than or equal to 4-point decrease in score.
- Tender and Swollen Joint Count ≥ 50% Improvement from Baseline at Weeks 8, 12, 24, 36, and 52 in Participants with ≥ 6 Tender and Swollen Joints Involving the Hands and Wrists at Baseline [ Time Frame: Baseline, Week 8, 12, 24, 36, and 52 ]
A 28-joint count will be used to evaluate the effect of efavaleukin alfa 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
- Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score ≥ 50% Improvement from Baseline at Week 8, 12, 24, 36, and 52 in Participants with a CLASI Activity Score ≥ 8 at Baseline [ Time Frame: Baseline, Week 8, 12, 24, 36, and 52 ]
To evaluate the effect of efavaleukin alfa on additional SLE efficacy endpoints
- Percent of Participants who Experience a Flare [ Time Frame: Week 52 ]
A flare is defined as a British Isles Lupus Assessment Group (BILAG) score designation of 'worse' or 'new'.
- Change from Baseline in Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS Fatigue SF 7A) Fatigue Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes
- Change from Baseline in Medical Outcomes Short Form-36 Questionnaire Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes
- Change from Baseline in Lupus Quality of Life (QoL) Questionnaire Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes
- Number of Participants who Experience a Treatment-Emergent Adverse Event (AE) and Serious Adverse Event (SAE) [ Time Frame: Up to Week 56 ]
To characterize the safety of efavaleukin alfa
- Number of Participants who Experience a Clinically Significant Change in Laboratory Values and Vital Sign Measurements [ Time Frame: Up to Week 56 ]
To characterize the safety of efavaleukin alfa
- Trough Serum and Sparse Postdose Serum Concentration of Efavaleukin Alfa [ Time Frame: Up to Week 52 ]
To characterize the pharmacokinetics (PK) of efavaleukin alfa
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Not Provided
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Not Provided
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Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus
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A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus With Inadequate Response to Standard of Care Therapy
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The primary objective is to evaluate the efficacy and safety of efavaleukin alfa in subjects with active systemic lupus erythematosus.
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Not Provided
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Interventional
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Phase 2
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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Active Systemic Lupus Erythematosus
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- Drug: Efavaleukin Alfa
Administered as a subcutaneous (SC) injection.
Other Name: AMG 592
- Drug: Placebo
Administered as a subcutaneous (SC) injection.
- Other: Standard of Care
Standard of care procedures and therapies for managing active systemic lupus erythematosus will be carried out according to each investigator's standard procedures.
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- Placebo Comparator: Placebo + Standard of Care
Interventions:
- Drug: Placebo
- Other: Standard of Care
- Experimental: Efavaleukin Alfa Dose Level One + Standard of Care
Interventions:
- Drug: Efavaleukin Alfa
- Other: Standard of Care
- Experimental: Efavaleukin Alfa Dose Level Two + Standard of Care
Interventions:
- Drug: Efavaleukin Alfa
- Other: Standard of Care
- Experimental: Efavaleukin Alfa Dose Level Three + Standard of Care
Interventions:
- Drug: Efavaleukin Alfa
- Other: Standard of Care
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Not Provided
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Terminated
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168
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320
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May 22, 2023
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May 22, 2023 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Participant has provided informed consent prior to initiation of any study specific activities/procedures.
- Participant is aged between 18 and 75.
- Fulfills classification criteria for systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE 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.
- British-Isles Lupus Assessment Group (BILAG) index score (BILAG 2004) of ≥ 1 A item or ≥ 2 B items.
- Must be taking ≥ 1 of the following SLE treatments (or regional equivalent): hydroxychloroquine, chloroquine, quinacrine, mycophenolate mofetil, azathioprine, methotrexate, dapsone, or oral calcineurin inhibitors, or OCS. A participant may enter the study on OCS alone (prednisone ≥ 10 mg/day or equivalent) only if the participant has previously documented trial of anti-malarial or immunosuppressant treatment for SLE. Participants must be on a stable dose for ≥ 8 weeks prior to screening for all antimalarials and immunosuppressants, with the exception of OCS doses which must be stable for ≥ 2 weeks prior to screening.
- For participants taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit and for ≥ 2 weeks prior to screening visit.
- Stability of SLE treatments: OCS and other immunosuppressants/immunomodulator agents and doses must be stable since screening visit.
- Disease activity: active disease as indicated by clinical hSLEDAI score ≥ 4 must be observed (clinical hSLEDAI score is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results including urine and immunologic parameters).
Exclusion Criteria:
Note: Abatacept is not considered a CTLA-4 inhibitor and is referred to below.
- Currently receiving or had treatment within 12 months prior to screening with T-cell depleting agents (eg, antithymocyte globulin, Campath).
- Currently receiving of had treatment with an interleukin 2 (IL-2) based therapy (eg, Proleukin).
- Current or previous treatment with a biologic agent with immunosuppressive/immunomodulatory activity as follows: rituximab within 6 months prior to screening; abatacept and belimumab within the past 3 months prior to screening; other biologics within < 5 drug half lives prior to screening.
- Participants who have received intraarticular, intralesional, or intramuscular corticosteroids within 2 weeks prior to screening or intravenous corticosteroids within 6 weeks prior to screening.
- Participants who have received live vaccines within 5 weeks prior to screening, or plan to receive live vaccines during the treatment period and up to 6 weeks after the end of treatment period in the study.
- Currently receiving treatment in another investigational device or drug study.
- Ending a treatment with an investigational drug or investigational device less than 3 months or 5 half-lives from the last dose of the investigational drug (whichever is longer) at screening.
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Sexes Eligible for Study: |
All |
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18 Years to 75 Years (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Austria, Bulgaria, Canada, Chile, Colombia, France, Greece, Hong Kong, Italy, Japan, Korea, Republic of, Mexico, Poland, Russian Federation, Spain, Switzerland, Taiwan, Turkey, United States
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NCT04680637
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20200234
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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. Further details are available at the URL below. |
URL: |
https://www.amgen.com/datasharing |
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Amgen
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Same as current
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Amgen
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Same as current
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Not Provided
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Amgen
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October 2023
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