Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Interventions
- Drug: Placebo for Rozibafusp Alfa
- Registration Number
- NCT04058028
- Lead Sponsor
- Amgen
- Brief Summary
The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ongoing disease activity despite treatment with standard of care therapies.
- Detailed Description
This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including oral corticosteroids (OCS), immunosuppressants and immunomodulators. Previous biologic use is allowed with an adequate washout period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 244
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo for Rozibafusp Alfa Placebo for Rozibafusp Alfa Placebo Investigational product solution in vial Rozibafusp Alfa, Dose A Rozibafusp Alfa Investigational product solution in vial Rozibafusp Alfa, Dose C Rozibafusp Alfa Investigational product solution in vial Rozibafusp Alfa, Dose B Rozibafusp Alfa Investigational product solution in vial
- Primary Outcome Measures
Name Time Method Number of Participants With a SLE Responder Index (SRI-4) Response at Week 52 Week 52 SRI-4 response at Week 52 is defined as a ≥ 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 score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3), and no use of more than protocol allowed therapies.
- Secondary Outcome Measures
Name Time Method Number of Participants With a SRI-4 Response at Week 24 Week 24 SRI-4 response at Week 24 is defined as a ≥ 4-point decrease in the hSLEDAI score, and no new BILAG 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in PGA (scale 0 to 3), and no use of more than protocol allowed therapies.
Number of Participants Who Achieved a BILAG Based Combined Lupus Assessment (BICLA) Response at Week 24 Week 24 The BICLA response is defined as:
1. An improvement in baseline BILAG domain scores across all body systems with moderate (domain B) or severe disease activity (domain A)
2. No new BILAG 2004 A domain score and no \> 1 new BILAG 2004 B domain scores compared with baseline
3. No worsening of the hSLEDAI score from baseline
4. No ≥ 0.3-point deterioration from baseline in PGA
5. No use of more than protocol-allowed therapies
6. No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants.Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52 Week 52 LLDAS was defined as meeting all the following conditions:
1. hSLEDAI ≤ 4, with no activity in major organ system (renal, central nervous system \[CNS\], cardiopulmonary, vasculitis, fever) and hemolytic anemia or gastrointestinal activity
2. No new lupus disease activity as compared with the previous assessment
3. PGA ≤ 1 (on a scale of 0 to 3)
4. Current prednisone or equivalent dose of ≤ 7.5 mg/day
5. Well-tolerated standard maintenance doses of immunosuppressive drugs and approved treatments, as allowed and specified in the protocol.Number of Participants Who Achieved a BICLA Response at Week 52 Week 52 The BICLA response is defined as:
1. An improvement in baseline BILAG domain scores across all body systems with moderate (domain B) or severe disease activity (domain A)
2. No new BILAG 2004 A domain score and no \> 1 new BILAG 2004 B domain scores compared with baseline
3. No worsening of the hSLEDAI score from baseline
4. No ≥ 0.3-point deterioration from baseline in PGA
5. No use of more than protocol-allowed therapies
6. No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants.Number of Participants Achieving a SRI-4 Response 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 Up to Week 52 SRI-4 response is defined as a ≥ 4-point decrease in the hSLEDAI score, and no new BILAG 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in PGA (scale 0 to 3), and no use of more than protocol allowed therapies. Participants also had to meet a reduction if OCS to ≤ 7.5 mg/day by Week 44 sustained through Week 52.
Annualized Moderate and Severe Flare Rate Over 52 Weeks as Measured by Safety of Estrogens in Systemic Lupus Erythematosus National Assessment [SELENA] -Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] Flare Index (SFI) Up to Week 52 The SFI, serves as a composite outcome measure incorporating the SELENA-SLEDAI score, and classifications of flares into mild, moderate, and severe, along with the PGA of disease activity. The SFI details specific clinical manifestations for each organ system and categorizes flares into mild, moderate, and severe based on treatment decisions. Moderate and severe flare: • Moderate: meeting criteria like SELENA-SLEDAI score change of 3 to 12 points, SLE symptom development, prednisone dose increase, non-steroidal anti-inflammatory drugs (NSAIDs)/hydrochloroquine addition, or PGA score increase by 1 to 2.5. • Severe: meeting criteria like SELENA-SLEDAI increase over 12 points, onset or worsening of severe symptoms, significant prednisone dose escalation, introduction of potent immunosuppressants, hospitalization, or PGA score reaching 2.5 or higher. Annualized flare rate was calculated as the number of flares divided by flare exposure time in days, multiplied by 365.25 for each Group.
Annualized Severe Flare Rate Over 52 Weeks as Measured by SFI Up to Week 52 The SFI, serves as a composite outcome measure incorporating the SELENA-SLEDAI score, and classifications of flares into mild, moderate, and severe, along with the PGA of disease activity. The SFI details specific clinical manifestations for each organ system and categorizes flares into mild, moderate, and severe based on treatment decisions. Severe flare: meeting criteria like SELENA-SLEDAI increase over 12 points, onset or worsening of severe symptoms, significant prednisone dose escalation, introduction of potent immunosuppressants, hospitalization, or PGA score reaching 2.5 or higher. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days, multiplied by 365.25 for each Group.
Annualized Flares Rate Over 52 Weeks 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 Up to Week 52 The BILAG flare index was derived from BILAG 2004, 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.
The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days, multiplied by 365.25 for each Group.Number of Participants With ≥6 Tender and Swollen Joints in Hands and Wrists at Baseline Achieving ≥50% Improvement From Baseline at Weeks 12, 24, 36, and 52 Week 12, 24, 36, and 52 The tender and swollen joint count is a physical assessment where for each swollen and tender joint a score of 1 is assigned. Scores are then summed up to provide a total score for both swollen and tender joints. Higher total score indicate a severe disease activity and a lower score indicates a lees severe disease activity.
Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score ≥8 at Baseline Achieving ≥50% Improvement From Baseline at Weeks 12, 24, 36, and 52 Week 12, 24, 36, and 52 The CLASI is an assessment tool consisting of two scores: one for disease activity and one for damage. Activity Score: Ranges from 0 to 70, and is assessed based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss, and non-scarring alopecia. Higher scores indicate more severe disease activity.
Damage Score: Ranges from 0 to 56, and is evaluated through dyspigmentation and scarring, including scarring alopecia. Dyspigmentation that remains visible for more than 12 months is considered permanent, and its score is doubled. Higher scores indicate greater damage.Change From Baseline in Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS-Fatigue SF7a) Score at Weeks 12, 24, 36, 44, and 52 Week 12, 24, 36, 44, and 52 The PROMIS-Fatigue SF7a is a 7-item instrument that assesses the experience of fatigue as well as its impact on physical, mental and social activities. Each item is scored on a 5-point Likert scale, ranging from "1" (Never) to "5" (Always). The scores of all 7 items are summed up with a total raw score range of 7(low level of fatigue)-35(high level of fatigue). Raw scores are converted to a T-score ranging from 29.4(low level of fatigue)-83.2(high level of fatigue).
Change From Baseline in the Short Form 36 Version 2 (SF-36v2) Health Survey Physical Component Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Mental Component Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Physical Functioning Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Physical Role Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Bodily Pain Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey General Health Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Vitality Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Social Role Functioning Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Emotional Role Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Mental Health Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in Lupus Quality of Life Questionnaire (LupusQoL) Score at Weeks 12, 24, 36, 44, and 52 Week 12, 24, 36, 44, and 52 The LupusQoL questionnaire consists of 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Each item in the questionnaire is scored on a 5 point scale and items within a given domain are summed and converted to a 0-100 scale. Each domain is scored 0-100 with higher scores representing better quality of life in the specific domain. Lower scores signify poorer quality of life within the domain.
Change From Baseline in Patient Global Assessment Score (PtGA) at Weeks 12, 24, 36, 44, and 52 Week 12, 24, 36, 44, and 52 The PtGA assesses disease activity on a 10 cm numeric rating scale (NRS; 0 to 10 cm). The scale for the assessment ranges from "very well" (0) to "very poor" (10).
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Up to approximately 68 weeks An adverse event (AE) was any negative medical occurrence linked to an intervention in humans, regardless of its relation to the intervention. Treatment-emergent AEs (TEAEs) were those that occurred after the first intervention dose. A serious adverse event (SAE) included outcomes such as death, life-threatening situations, hospitalization or an extended hospital stay, significant incapacity, congenital defects, or other crucial medical events. AE severity followed the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 scale: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death). Clinically significant laboratory results or other assessments (e.g., ECGs, scans, vital signs) that worsened from baseline and were deemed important by the investigator, independent of disease progression, were also considered.
Serum Concentration of Rozibafusp Alfa Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 36, Week 44, Week 52, Week 56, Week 60, Week 64, and Week 68 Terminal Half-life of Rozibafusp Alfa Up to Week 68
Trial Locations
- Locations (142)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Imaging Endpoints
🇺🇸Scottsdale, Arizona, United States
Medvin Clinical Research
🇺🇸Covina, California, United States
Southern California Permanente Medical Group
🇺🇸Fontana, California, United States
University of California San Diego
🇺🇸La Jolla, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Stanford University Hospitals and Clinics
🇺🇸Palo Alto, California, United States
TriWest Research Associates
🇺🇸San Diego, California, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Scroll for more (132 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States