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

Phase 2TerminatedNCT04680637

Amgen168 enrolled

Overview

The primary objective is to evaluate the efficacy and safety of efavaleukin alfa in subjects with active systemic lupus erythematosus.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

168

Conditions

Active Systemic Lupus Erythematosus

Interventions

Efavaleukin AlfaDRUG

Administered as a subcutaneous (SC) injection.

PlaceboDRUG

Administered as a subcutaneous (SC) injection.

Standard of CareOTHER

Standard of care procedures and therapies for managing active systemic lupus erythematosus will be carried out according to each investigator's standard procedures.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (150)

Outcomes

Primary Outcomes

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

A participant achieved an SRI-4 response if all the following criteria were met: * ≥ 4-point reduction from baseline in Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score (scale 0-105, with higher scores indicating more disease activity). * No new British-Isles Lupus Assessment Group (BILAG) A score and no \> 1 new BILAG B organ domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). * \< 0.3-points deterioration from baseline in Physician Global Assessment (PGA) visual analogue (VAS) score (scale 0 to 3, with higher scores indicating more severe disease). Participants were considered non-responders for using more than protocol-permitted therapies.

Time frame: Week 52

Secondary Outcomes

Number of Participants Who Achieved a BILAG-based Composite Lupus Assessment (BICLA) Response at Week 52

A participant achieved a BICLA response if all the following criteria were met: * At least 1 gradation of improvement in baseline BILAG domain scores in all body systems with moderate or severe disease activity at entry and no \> 1 BILAG B domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). * No worsening of the hSLEDAI score from baseline (scale 0-105, with higher scores indicating more disease activity). * \< 0.3-points deterioration from baseline in PGA VAS (scale 0 to 3, with higher scores indicating more severe disease). * No initiation of non-protocol treatment.

Time frame: Week 52

Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52

A participant achieved an LLDAS response if all the following criteria were met: * hSLEDAI ≤ 4 (scale 0-105, higher scores indicating more disease activity) with no activity in major organ systems (renal \[proteinuria, hematuria, pyuria, urinary casts\], central nervous system \[seizure, psychosis, organic brain syndrome, cranial nerve disorder, cerebrovascular accident\], cardiopulmonary \[pericarditis, pleurisy\], vasculitis and fever) \& no hemolytic anemia or gastrointestinal activity in BILAG. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active) to E (never present). * No new lupus disease activity compared with previous assessment defined as no new descriptor scores in hSLEDAI. * A score of \< 1 in PGA VAS score (scale 0 to 3, with higher scores indicating more severe disease). * Current prednisolone dose ≤ 7.5 mg daily. * No increase or initiation of immunosuppressive drugs.

Data from ClinicalTrials.gov

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University of Alabama at Birmingham,Arthritis Clinical Intervention Program

Birmingham, Alabama, United States

Arizona Arthritis and Rheumatology Associates PC

Gilbert, Arizona, United States

Arizona Arthritis And Rheumatology Associates PC

Glendale, Arizona, United States

Arizona Arthritis and Rheumatology Associates PC

Tucson, Arizona, United States

Loma Linda University Health Care

Loma Linda, California, United States

University of California Los Angeles

Los Angeles, California, United States

University of California Irvine

Orange, California, United States

Robin K Dore MD Inc

Tustin, California, United States

Arthritis and Rheumatic Disease Specialties

Aventura, Florida, United States

Life Clinical Trials

Aventura, Florida, United States

...and 140 more locations

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

Participants taking OCS could begin tapering OCS after the Week 12 assessment up to the Week 44 assessment with initiation of tapering based upon clinical judgement of the treating physician. The tapering schedule was at the discretion of the investigator but should not have been tapered more than 20% of the prior dose per week. Tapering OCS before Week 12 was not encouraged but may have been allowed based upon investigator's judgement. Between weeks 44 and 52, the OCS dosing must again have remained stable.

Time frame: Baseline to Week 52

Number of Participants Who Achieved a SRI-4 Response at Week 24

A participant achieved an SRI-4 response if all the following criteria were met: * ≥ 4-point reduction from baseline in hSLEDAI score (scale 0-105, with higher scores indicating more disease activity). * No new BILAG A score and no \> 1 new BILAG B organ domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). * \< 0.3-points deterioration from baseline in PGA VAS score (scale 0 to 3, with higher scores indicating more severe disease). Participants were considered non-responders for using more than protocol-permitted therapies.

Time frame: Week 24

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

The hSLEDAI is a global index that evaluates disease activity and includes both laboratory and clinical parameters. The score ranges from 0 to 105, with higher scores indicating more disease activity. A participant achieved a hSLEDAI response if there was a ≥ 4-point reduction in hSLEDAI from baseline.

Time frame: Week 24 and 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

The swollen and tender join count assessments were performed at the site by an experienced independent and blinded joint evaluator. Joints in hands and wrists were scored for the simultaneous presence (1) or absence (0) of swelling and tenderness. Scores ranged from 0-28. A higher score indicates more severe disease.

Time frame: Weeks 8, 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

The CLASI consists of 2 scores, the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The total score ranges from 0-70, with higher scores indicating more severe disease.

Time frame: Weeks 8, 12, 24, 36 and 52

Annualized Flare Rate Over 52 Weeks

A flare was defined as a BILAG score designation of "worse" or "new" resulting in a B score in ≥ 2 organs or an A score in ≥ 1 organ. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied by 365.25.

Time frame: Up to 52 weeks

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

The PROMIS Fatigue SF 7a assesses the experience of fatigue as well as its impact on physical, mental and social activities. The score ranges from 7 to 35, with higher scores indicating more fatigue. A negative change from baseline indicates a reduction in fatigue. Efficacy data collected after the study termination decision date were censored and excluded from analyses for that particular visit.