Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)

Amgen244 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

244

Conditions

Systemic Lupus Erythematosus (SLE)

Interventions

Rozibafusp AlfaDRUG

Rozibafusp Alfa will be presented in 5 mL glass vial

Placebo for Rozibafusp AlfaDRUG

Placebo for Rozibafusp Alfa will be presented in 5 mL glass vial

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria Screening Visit: * Subject has provided informed consent prior to initiation of any study-specific activities/procedures. * Age ≥ 18 years to ≤ 75 years at screening visit. * Fulfills classification criteria for SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE (Aringer et al, 2019), 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. * Additional protocol-specific rules are applied at screening and throughout the study, as follows: * Arthritis: Arthritis (at least 3 tender and swollen joints) must involve joints in the hands or wrists for the hSLEDAI scoring. * Alopecia: Subjects should have hair loss without scarring; should neither have alopecia areata nor androgenic alopecia; and should have a CLASI activity score for alopecia ≥ 2. * Oral ulcers: Ulcers location and appearance must be documented by the investigator. * Scleritis and Episcleritis: the presence of stable SLE-related scleritis and episcleritis must be documented by an ophthalmologist and other causes excluded. * Renal: subjects with urine protein/creatinine ratio \< 3000 mg/g (or equivalent method) in a clear catch spot urine sample can enroll and be scored in the hSLEDAI, provided the subject has a clinical hSLEDAI ≥ 4 and did not receive induction treatment for nephritis within the last year. * Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be accompanied by objective findings to be scored in the hSLEDAI. * Unless there is a documented intolerance, subjects must be taking: * Only 1 of the following SLE treatments: anti-malarial (hydroxychloroquine, chloroquine, or quinacrine), azathioprine, methotrexate, leflunomide, mycophenolate mofetil/acid mycophenolic, or dapsone. OR • 2 of the above-mentioned SLE treatments in which 1 must be anti-malarial (hydroxychloroquine, chloroquine, or quinacrine). * Treatment should be taken for ≥ 12 weeks prior to screening and must be a stable dose for ≥ 8 weeks prior to screening. * For subjects taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit for ≥ 2 weeks prior to screening visit. Exclusion Criteria Screening Visit Subjects are excluded from the study if any of the following criteria apply: Disease Related * Urine protein creatinine ratio ≥ 3000 mg/g (or equivalent) at screening or induction therapy for lupus nephritis within 1 year prior to screening visit. * 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.

Locations (147)

Outcomes

Primary Outcomes

Number of Participants With a SLE Responder Index (SRI-4) Response at 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.

Time frame: Week 52

Secondary Outcomes

Number of Participants With a SRI-4 Response at 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.

Time frame: Week 24

Number of Participants Who Achieved a BILAG Based Combined Lupus Assessment (BICLA) Response at 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.

Time frame: Week 24

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

Data from ClinicalTrials.gov

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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

...and 137 more locations

Number of Participants Who Achieved a BICLA Response at Week 52

Time frame: Week 52

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

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.

Time frame: Up to 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)

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.

Time frame: Up to Week 52

Annualized Severe Flare Rate Over 52 Weeks as Measured by SFI

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.

Time frame: Up to Week 52

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

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.

Time frame: Up to Week 52

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

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.

Time frame: Week 12, 24, 36, and 52

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

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.

Time frame: Week 12, 24, 36, and 52

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

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).