Efficacy and Safety of Efavaleukin Alfa in Subjects with Active Systemic Lupus Erythematosus

• Register: EUCTR
• Last refreshed on: 10 February 2025
• Main ID: EUCTR2020-003509-72-GR
• Date of registration: 22/04/2021
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc.
• Public title: Efficacy and Safety of Efavaleukin Alfa in Subjects with Active Systemic Lupus Erythematosus
• Scientific title: 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 (VIOLET)
• Date of first enrolment: 17/06/2021
• Target sample size: 320
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003509-72
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Bulgaria, Canada, Chile, Colombia, France, Greece, Hong Kong, Italy, Japan, Mexico, Poland, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Turkey, United States

Contacts

• Name: Medical Information
• Affiliation: Amgen Hellas ?.?.?.

• Name: Medical Information
• Affiliation: Amgen Hellas ?.?.?.

Key inclusion & exclusion criteria

Inclusion criteria:
Screening:
101 Subject has provided informed consent prior to initiation of any
study specific activities/procedures.
102 Age = 18 years to 75 years at screening.
103 Fulfills classification criteria for SLE according to the 2019
EULAR)/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 Phadia method will be used for the purposes of hSLEDAI scoring during screening and throughout the study.
110 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 and immunologic parameters. Including the following protocol specific rules:
- Arthritis: for hSLEDAI scoring purposes, a minimum of 3 joints with
pain and signs of inflammation (ie, tenderness with swelling or effusion) must involve small joints in the hands, wrists, or a combination of joints in hands and wrists.
- Alopecia: subjects should have active hair loss without scarring; should neither have alopecia areata nor androgenic alopecia; and should have a CLASI activity score for alopecia
- 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 < 2000 mg/g (or
equivalent) in a clean catch spot urine sample can enroll and be scored
in the hSLEDAI, provided the subject has a clinical hSLEDAI = 4.
- Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be accompanied by objective findings to be scored in the hSLEDAI.
105 BILAG index score (BILAG 2004) of = 1 A item or = 2 B items.
106 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 subject may enter the study on OCS alone (prednisone = 10 mg/day or equivalent) only if the subject has previously documented trial of anti-malarial or immunosuppressant treatment for SLE. Subjects 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.
107 For subjects taking OCS, the dose must be = 20 mg/day of
prednisone or OCS equivalent, and the dose must be stable for = 2 weeks prior to screening visit.
Day 1 (Baseline):
The baseline/day 1 visit should occur after confirmation of eligibility by the adjudication team within 33 days after the screening visit. At the baseline/day 1 visit, the following 2 criteria should be assessed prior to randomization:
108 Stability of SLE treatments: OCS and other
immunosuppressants/immunomodulator agents and doses must be
stable since screening visit.
109 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)
Are the trial subject
Exclusion criteria:
231 Lupus nephritis if any of the following are present:
urine protein creatinine ratio = 2000 mg/g at screening, OR requiring induction therapy currently or within 1 year prior to screening, OR
histological evidence of diffuse proliferative glomerulonephritis within 12 weeks prior to screening.
202 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.
232 Currently present or within 1 year prior to screening a diagnosis of any chronic inflammatory disease other than SLE which would interfere with SLE disease assessment.
204 History of any disease other than SLE that has required treatment with oral or parenteral corticosteroids for > 2 weeks within 4 months prior to screening.
205 Active infection for which anti-infectives are indicated currently or within 4 weeks prior to screening visit OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to screening visit.
206 Active tuberculosis or latent tuberculosis with no documented past history of adequate treatment per local standard of care.
207 Positive test for tuberculosis during screening defined as: either a positive or indeterminate QuantiFERON®-TB or T-spot test OR positive purified protein derivative (PPD) (= 5 mm of induration at 48 to 72 hours after test is placed).
233 Positive for hepatitis B surface antigen (HBsAg); or positive for
hepatitis B core antibody (HBcAb). A positive history of hepatitis B surface antibody (HBsAb) vaccination without history of hepatitis B infection (ie, positive HBsAg), negative HBsAg and negative HBcAb is allowed.
234 Positive for hepatitis C antibody
210 Known history of HIV or positive HIV test at screening.
235 Presence of 1 or more significant concurrent medical conditions,
including but not limited to the following: poorly controlled diabetes or hypertension symptomatic heart failure myocardial infarction or
unstable angina pectoris within the past 12 months severe chronic
pulmonary disease requiring oxygen therapy multiple sclerosis or any
other demyelinating disease
212 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 breast ductal carcinoma in situ > 5 years of screening
213 Currently receiving or had treatment with: cyclophosphamide,
chlorambucil, nitrogen mustard, or any other alkylating agent within 6 months prior to screening or sirolimus within 4 weeks prior to screening.
237 Currently receiving or had treatment with a Janus kinase (JAK)
inhibitor within less than 5 drug half-lives prior to screening.
215 Currently receiving or had treatment with an immune checkpoint
inhibitor
216 Currently receiving or had treatment within 12 months prior to
screening with T-cell depleting agents
217 Currently receiving or had treatment with an IL-2 based therapy
238 Current or previous treatment with a biologic agent with
immunosuppressive/immunomodulatory activity as follows: rituximab within 6 months prior to screening; abatacept, belimumab, and anifrolumab within the past 3 months prior to screening; other biologics within < 5 drug half-lives prior to screening.
219 Subjects who have received intraarticular, intralesional, or
intramuscularcorticosteroids within 2 weeks

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Immune system processes [G12]

Active Systemic Lupus Erythematosus
MedDRA version: 21.1 Level: LLT Classification code 10025139 Term: Lupus erythematosus systemic System Organ Class: 100000004859

Intervention(s)

Product Name: Efavaleukin Alfa
Product Code: AMG 592
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: EFAVALEUKIN ALFA
Current Sponsor code: AMG 592
Other descriptive name: RECOMBINANT FACTOR FC FUSION PROTEIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): - SRI-4 response at week 52

Secondary Objective: - Evaluate the efficacy of efavaleukin alfa at week 52, as measured by the BICLA index responses
- Evaluate the efficacy of efavaleukin alfa at week 52, as measured by LLDAS response
- Evaluate the efficacy of efavaleukin alfa at week 52, as measured by OCS tapering
- Evaluate the efficacy of efavaleukin alfa at week 24, as measured by SRI-4 response
- Evaluate the efficacy of efavaleukin alfa at week 24, as measured by the BICLA index responses
- Evaluate the efficacy of efavaleukin alfa at weeks 24 and 52, as measured by hSLEDAI
- Evaluate the efficacy of efavaleukin alfa on joints and skin
- Evaluate the efficacy of efavaleukin alfa using BILAG score
- Evaluate the efficacy of efavaleukin alfa using patient reported outcomes
- Characterize the safety of efavaleukin alfa
- Characterize the PK of efavaleukin alfa

Timepoint(s) of evaluation of this end point: Week 52

Main Objective: Evaluate the efficacy of efavaleukin alfa at week 52, as measured by the SRI-4 response

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 8, 12, 24, 36, and 52

Secondary end point(s): - BICLA response at week 52
- LLDAS response at week 52
- Reduction of OCS to = 7.5 mg/day by week 44 and sustained through week 52 in subjects with a baseline OCS dose = 10 mg/day
- SRI-4 response at week 24
- BICLA response at week 24
- hSLEDAI response (ie, reduction = 4 points from baseline) at
week 24
? hSLEDAI response (ie, reduction = 4 points from baseline) at
week 52
- Improvement from baseline in tender and swollen joint count
= 50% at weeks 8, 12, 24, 36, and 52 in subjects with = 6 tender and
swollen joints involving in hands and wrists at baseline
- Improvement from baseline in CLASI activity score = 50% at
week 8, 12, 24, 36, and 52 in subjects with a CLASI activity
score = 8 at baseline
- Annualized flare rate (as 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
- Change from baseline in fatigue standardized score using the PROMIS Fatigue SF 7a at week 12, 24, 36, and 52
- Change from baseline in the physical component score, mental
component score and individual domains of the SF 36 v2 at week
12, 24, 36, and 52
- Change from baseline in the domain scores on the Lupus QoL
at weeks 12, 24, 36, and 52
- Treatment-emergent adverse events
- Serious adverse events
- Clinically significant changes in laboratory values and vital signs
- Trough and sparse post-dose serum concentrations of efavaleukin alfa

Secondary ID(s)

20200234

NCT04680637

2020-003509-72-FR

Source(s) of Monetary Support

Amgen Inc.

Ethics review

Status: Approved
Approval date: 17/06/2021
Contact:

Results

• Results available: Yes
• Date Posted: 07/06/2024
• Date Completed: 24/05/2023
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003509-72/results