Trial Outcomes & Findings for Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus (NCT NCT04680637)

Participants were enrolled at 73 centers in 13 countries (Bulgaria, Chile, Colombia, Greece, Italy, Japan, Mexico, Poland, Russian Federation, Spain, Switzerland, Taiwan, and the United States) between 06 May 2021 and 24 May 2023.

A total of 464 participants were screened, of which 168 participants were enrolled and received efavaleukin alfa.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1. Limitations in physical activities because of health problems. 2. Limitations in social activities because of physical or emotional problems. 3. Limitations in usual role activities because of physical health problems. 4. Bodily pain. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perceptions. The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a systemic lupus erythematosus (SLE)-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1. Physical health. 2. Pain. 3. Planning. 4. Intimate relationships. 5. Burden to others. 6. Emotional health. 7. Body image. 8. Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes.

A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment and had emerged or worsened during treatment. A serious TEAE was defined as any untoward medical occurrence that, met at least 1 of the following criteria: * Resulted in death (fatal). * Was immediately life-threatening. * Required in-patient hospitalization or prolongation of existing hospitalization. * Resulted in persistent or significant disability/incapacity. * Was a congenital anomaly/birth defect. * Was any other medically important serious event. Clinically significant changes from baseline in laboratory values and vital signs were also recorded as TEAEs.

Serum efavaleukin alfa concentrations by timepoint after multiple dose subcutaneous administration of efavaleukin alfa to participants with active systemic lupus erythematosus. Lower limit of quantification= 0.100 ng/mL.