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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 July 2024
• Main ID: NCT04680637
• Date of registration: 18/12/2020
• Prospective Registration: Yes
• Primary sponsor: Amgen
• 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
• Date of first enrolment: May 6, 2021
• Target sample size: 168
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT04680637
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: MD
• Affiliation: Amgen

Key inclusion & exclusion criteria

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:

- Lupus nephritis if any of the following are present: urine protein creatinine ratio
= 2000 mg/g (or equivalent) at screening, OR requiring induction therapy currently
or within 1 year prior to screening, OR histological evidence (if available) of
diffuse proliferative glomerulonephritis within 12 weeks prior to screening.

- 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.

- Currently present or within 1 year prior to screening a diagnosis of any chronic
inflammatory disease other than SLE (eg, rheumatoid arthritis) which would interfere
with SLE disease assessment.

- 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.

- Active infection (including chronic or localized infections) 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.

- Active tuberculosis or latent tuberculosis with no documented past history of
adequate treatment per local standard of care.

- Positive test for tuberculosis during creening 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).

- Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core
antibody (HBcAb). A history of hepatitis B vaccination without history of hepatitis
B infection (ie, positive hepatitis B surface antibody (HBsAb), negative HBsAg and
negative HBcAb) is allowed.

- Positive for hepatitis C antibody.

- Known history of HIV or positive HIV test at screening.

- Presence of 1 or more significant concurrent medical conditions, including but not
limited to the following:

- poorly controlled diabetes (hemoglobin A1C > 7) or hypertension

- symptomatic heart failure (New York Heart Association class III or IV)

- myocardial infarction or unstable angina pectoris within the past 12 months
prior to screening

- severe chronic pulmonary disease requiring oxygen therapy

- multiple sclerosis or any other demyelinating disease

- 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

- 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 screening.

- Currently receiving or had treatment with a Janus kinase (JAK) inhibitor within 3
months or less than 5 drug half-lives (whichever is longer) prior to screening.

- Currently receiving or had treatment with an immune checkpoint inhibitor (eg,
programmed death 1 [PD-1] inhibitor, programmed death ligand 1 [PD-L1] inhibitor,
cytotoxic T-lymphocyte associated protein 4 [CTLA-4] inhibitor).

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.


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Active Systemic Lupus Erythematosus

Intervention(s)

Drug: Efavaleukin Alfa

Drug: Placebo

Other: Standard of Care

Primary Outcome(s)

Number of Participants Who Achieved a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response at Week 52 [Time Frame: Week 52]

Secondary Outcome(s)

Change From Baseline in Fatigue Standardized Score Using the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Instrument at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Physical Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Vitality Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Bodily Pain Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Physical Component Score of the Medical Outcomes Short Form-36 Questionnaire Version 2 (SF-36V2) at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Burden to Others Domain Score of the LupusQoL at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Pain Domain Score of the LupusQoL at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Planning Domain Score of the LupusQoL at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Number of Participants Who Achieved a BILAG-based Composite Lupus Assessment (BICLA) Response at Week 52 [Time Frame: Week 52]

Annualized Flare Rate Over 52 Weeks [Time Frame: Up to 52 weeks]

Change From Baseline in the Body Image Domain Score of the LupusQoL at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Number of Participants With a Reduction of Oral Corticosteroids (OCS) 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: Baseline to Week 52]

Number of Participants With an Improvement From Baseline in Tender and Swollen Joint Count = 50% at Weeks 8, 12, 24, 36, and 52 in Participants With = 6 Tender and Swollen Joints in Hands and Wrists [Time Frame: Weeks 8, 12, 24, 36 and 52]

Change From Baseline in the General Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Mental Component Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Fatigue Domain Score of the LupusQoL at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Intimate Relationship Domain Score of the LupusQoL at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Emotional Health Domain Score of the LupusQoL at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Change From Baseline in the Mental Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Number of Participants Who Achieved a BICLA Response at Week 24 [Time Frame: Week 24]

Number of Participants With a hSLEDAI Response at Week 24 and Week 52 [Time Frame: Week 24 and Week 52]

Change From Baseline in the Physical Health Domain Score of the Lupus Quality of Life (LupusQoL) at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Number of Participants With an Improvement From Baseline in Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score = 50% at Week 8, 12, 24, 36, and 52 in Participants With a CLASI Activity Score = 8 at Baseline [Time Frame: Weeks 8, 12, 24, 36 and 52]

Change From Baseline in the Social Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52 [Time Frame: Week 52]

Change From Baseline in the Emotional Role Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [Time Frame: Day 1 to Week 56]

Serum Efavaleukin Alfa Concentrations by Timepoint [Time Frame: Day 1: 6-24 and 48-96 hrs, Day 29, Day 43: 6-24 and 48-96 hrs, Day 85, Day 169, Day 253, Day 309, and Day 365]

Change From Baseline in the Physical Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52 [Time Frame: Baseline to Week 12, 24, 36 and 52]

Number of Participants Who Achieved a SRI-4 Response at Week 24 [Time Frame: Week 24]

Secondary ID(s)

20200234

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/06/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT04680637