Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care

Phase 1

Completed

Conditions: Systemic Lupus Erythematosus

Interventions: Drug: Placebo
Drug: BOS161721

Registration Number: NCT03371251

Lead Sponsor: Boston Pharmaceuticals

Brief Summary: This study will be conducted to assess the safety, tolerability, and immunogenicity of repeat doses of BOS161721 (20 milligrams \[mg\], 60 mg, and 120 mg) administered subcutaneously in adult participants with moderately to severely active Systemic Lupus Erythematosus (SLE) on limited background standard of care treatment, in order to estimate the optimal dose.

BOS161721 at the chosen dose will be compared to placebo for response on the SLE Responder Index 4, with sustained reduction of oral corticosteroids, in the same participant population.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 143

Inclusion Criteria

Men and women, ages 18 to 70 years, inclusive
Participants must be mentally capable of giving consent and there must be evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study
Participants must have Systemic Lupus Erythematosus (SLE) as defined by meeting 4 of the Systemic Lupus International Collaborating Clinics classification criteria for SLE (with at least 1 clinical and 1 immunologic criterion OR Lupus nephritis as the sole clinical criterion in the presence of anti-nuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) antibodies), either sequentially or simultaneously
At screening, participants must have at least 1 of the following:
1. Elevated ANA ≥ 1:80 via immunofluorescent assay at the central laboratory
2. Positive anti-dsDNA or anti-Smith (anti-Sm) above the normal level as determined by the central laboratory
At screening, the total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score must be ≥ 8, including points from at least 1 of the following clinical components:

a. Arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, and vasculitis Note: Points from lupus headache and organic brain syndrome will also be excluded from qualifying total and clinical SLEDAI-2K scores at screening and Day 0.
A clinical SLEDAI-2K score of ≥ 6 at screening at Day 0. Clinical SLEDAI-2K score is defined as follows:
1. Contains points from arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, or vasculitis
2. Excludes parameters which require central laboratory results: hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA, decreased complement, thrombocytopenia, and leukopenia Note: Points from lupus headache and organic brain syndrome will also be excluded from qualifying total and clinical SLEDAI-2K scores at screening and Day 0.
Participants must have at least 1 qualifying A or 2Bs from the following manifestations of SLE, as defined by the British Isles Lupus Assessment Group (BILAG) criteria as modified for use in this study, which must be confirmed by the central data reviewer:
1. BILAG A or B score in the mucocutaneous body system. If a BILAG B score is due to BILAG number 6, mild skin eruption, the CLASI activity score including erythema and scale/hypertrophy must be ≥ 3 excluding points from mucosal ulcers and alopecia.
2. BILAG A or B score in the musculoskeletal body system due to active polyarthritis Note: Hips, shoulders, back, neck, and temporomandibular joints do not count towards the total number of joints with active synovitis.

If only one "B" and no "A" score is present in the mucocutaneous body system or in the musculoskeletal body system due to arthritis, then at least 1 "B" must be present in at least 1 other body system for a total of 2 "B" BILAG body system scores.

Participants must be currently receiving at least 1 of the following:

Administration for a minimum of 12 weeks, and a stable dose for at least 56 days (8 weeks prior to Day 0) of the following permitted steroid sparing agents: azathioprine (AZA), mycophenolate mofetil or mycophenolic acid, chloroquine, hydroxychloroquine, or methotrexate
If AZA, myocophenolate mofetil, mycophenolic acid, hydroxychloroquine, or MTX were discontinued prior to screening, the washout period must be ≥ 12 weeks.
Corticosteroids (CSs) (prednisone or prednisone-equivalent) at a stable dose of up to 30 mg/day for at least 6 weeks prior to Day 0

i. For participants whose only SLE treatment is CSs, the stable CS dose must be ≥ 10 mg/day for at least 6 weeks prior to Day 0 and no more than 30 mg/day at the time of randomization.

ii. Topical steroids may be used, but the dose must be stable for at least 6 weeks prior to Day 0. PRN topical steroids are not permitted.

Women of childbearing potential (WOCBP):
1. Must have a negative serum pregnancy test at screening. Urine pregnancy test must be negative prior to first dose
2. Must not be breastfeeding
3. Must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 52 weeks
Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 52 weeks
Participants must demonstrate willingness and ability to comply with the scheduled study visits, treatment plans, laboratory tests, and other procedures

Exclusion Criteria

Participants presenting with any of the following will not be included in this study:

Drug-induced SLE, rather than "idiopathic" SLE
Other systemic autoimmune disease (eg, erosive arthritis, rheumatoid arthritis [RA], multiple sclerosis [MS], systemic sclerosis, or vasculitis not related to SLE). RA-Lupus overlap (Rupus), and secondary Sjogren syndrome are allowed.
Any major surgery within 6 weeks of study drug administration (Day 0) or any elective surgery planned during the course of the study
Any history or risk for tuberculosis (TB), specifically those with:
1. Current clinical, radiographic, or laboratory evidence of active TB
2. History of active TB
3. Latent TB defined as positive QuantiFERON-TB Gold In Tube or other diagnostic test in the absence of clinical manifestations. Latent TB is not excluded if the participant has documented completion of adequate course of prophylactic treatment with regimen recommended by local health authority guideline, or the participant has started treatment with isoniazid, or other regimen recommended by local health authority guidelines for at least 1 month before Day 0 and continues to receive the prophylactic treatment during study until the treatment course is completed
Active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG A criteria, with the exception of mononeuritis multiplex and polyneuropathy, which are allowed
Severe proliferative lupus nephritis (World Health Organization Class III, IV), which requires or may require induction treatment with cytotoxic agents or high dose CSs
Concomitant illness that, in the opinion of the investigator or the Sponsor or their designee, is likely to require additional systemic glucocorticosteroid therapy during the study, (eg, asthma), is exclusionary. However, treatment for asthma with inhalational CSs therapy is allowed.
Use or planned use of concomitant medication outside of standard of baseline treatment for SLE from Day -1 or for any time during the study
Active and clinically significant infection (bacterial, fungal, viral, or other) within 60 days prior to first dose of study drug. Clinically significant is defined as requiring systemic parenteral antibiotics or hospitalization
A history of opportunistic infection, or a history of recurrent or severe disseminated herpes zoster or disseminated herpes simplex within the last 3 years
Chronic viral hepatitis B (HBV) and hepatitis C (HCV), unless participant received curative treatment for HCV and has a documented negative viral load, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
Cryptosporidium in the stool sample at screening
White blood cells < 1,200/millimeters cubed (mm^3) (1.2 × 10^9/Liter [L]) at screening
Absolute neutrophil count < 500/mm^3 at screening
CD4+ count < 150/microliter (µL) at screening
Platelets < 50,000/mm^3 (50 × 10^9/L) or < 35,000/mm^3 (35 × 10^9/L) if related to SLE, at screening
Hemoglobin < 8 grams per deciliter (g/dL) or < 7 g/dL at screening if related to SLE
Proteinuria > 3.0 g/day (3000 milligrams per day [mg/day]) at screening or equivalent level of proteinuria as assessed by protein/creatinine ratio (3 mg/mg or 339 milligrams per millimole [mg/mmol])
Serum creatinine > 2.0 mg/dL at screening or creatinine clearance < 40 milliliters per minute (mL/minute) based on Cockcroft-Gault calculation
Serum alanine aminotransferase and/or serum aspartate aminotransferase > 2 × the upper limit of normal (ULN) at screening, unless explicitly related to lupus based on the investigator's judgment
Creatinine kinase > 3.0 × ULN at screening unless related to lupus myositis
Total bilirubin > 1.5 × ULN at screening (unless related to Gilbert's syndrome)
Any other laboratory test results that, in the opinion of the Investigator or the Sponsor or Sponsor's designee, might place a participant at unacceptable risk for participating in this study
History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibodies (mAb) (eg, IgG protein) or molecules made of components of mAbs
History substance and/or alcohol abuse, or dependence within the past 1 year, at the investigator's judgment
History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell cancer, or cervical cancer in situ resolved by excision)
Any other severe acute or chronic medical or psychiatric condition, including recent (within the past year) medical conditions (eg, cardiovascular conditions, respiratory illnesses) that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, Sponsor, or Sponsor's designee, would make the participant inappropriate for entry into this study
Investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the investigator, or participants who are employees of the sponsor or directly involved in the conduct of the trial
Currently participating in, or who have participated in other interventional (drug or device) clinical study within 30 days or 5 half-lives of baseline, whichever is longer
Recent (within the past 12 months) or active suicidal ideation or behavior based on participant responding "yes" to question 3, 4, or 5 on the Columbia Suicide severity Rating Scale
Current or pending incarceration
Current or pending compulsory detainment for treatment of either a psychiatric or physical (eg, infectious disease) illness
Currently taking a total daily dose of > 30 mg morphine or morphine equivalent
Body mass index (BMI) ≥ 40.0

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1b: Placebo 20, 60, 120 mg	Placebo	Participants will be randomized to receive a 20 mg, 60 mg, or 120 mg SC dose of placebo. Participants may receive a total of 7 SC monthly doses of placebo on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.
Phase 2: Placebo	Placebo	Participants will be randomized to receive a 120 mg SC dose of placebo (as determined from Phase 1b of the study). Participants may receive a total of 7 SC monthly doses of placebo on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.
Phase 1b: BOS161721 20, 60, 120 mg	BOS161721	Participants will be randomized to receive a 20 milligram (mg), 60 mg, or 120 mg subcutaneous (SC) dose of BOS161721. Participants may receive a total of 7 SC monthly doses of BOS161721 on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.
Phase 2: BOS161721	BOS161721	Participants will be randomized to receive a 120 mg SC dose of BOS161721 (as determined from Phase 1b of the study). Participants may receive a total of 7 SC monthly doses of BOS161721 on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.

Primary Outcome Measures

Name	Time	Method
Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210	Day 210	The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group (BILAG) 2004 Index and the Physician's Global Assessment (PGA). Response based on the SRI-4 is defined by: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B) compared with baseline; and 3) no deterioration from baseline in the PGA by ≥ 30 millimeters. The SLEDAI-2K total score falls between 0 and 105, with higher scores representing increased disease activity.The SRI-4 response in participants with moderate to severe SLE is associated with broad improvements in clinical and participant-reported outcomes.
Phase 1b: Number of Participants With Adverse Events (AEs)	Up to Day 270	The safety, tolerability, and immunogenicity of repeat doses of BOS161721 (20, 60, and 120 mg) administered SC were assessed in adult participants with moderate to severe SLE on limited background standard of care treatment, in order to estimate the optimal dose.

Secondary Outcome Measures

Name	Time	Method
Phase 1b: Terminal Elimination Half-life (t1/2)	Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180	The PK of BOS161721 was characterized and the optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F)	Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180	The PK of BOS161721 was characterized and the optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG)	Baseline (Day 0); Day 180	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 2: Mean Change From Baseline in PGA	Baseline, Day 210	The PGA is used to assess Investigator's general impression on the patient's overall status of SLE disease activity via visual analogue scale (100 mm) with 0 being "very good, asymptomatic and no limitation of normal activities" with 100 mm being "most severe possible disease ever seen in all SLE patients".
Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3)	Baseline (Day 0); Days 30, 44, 60, and 90 (pre-dose [trough] samples only)	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and pharmacodynamic (PD) data in participants with moderate to severe SLE.
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit	Days 30, 60, 90, 120, 150, 180, 210, 240, and 270	The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) 2004 Index. Response based on the SRI-4 is defined by: 1) ≥ 4-point reduction in the SLEDAI-2K global score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B); and 3) no deterioration from baseline in the Physician's Global Assessment (PGA) by ≥ 30 millimeters. The SRI-4 response in participants with moderate to severe SLE is associated with broad improvements in clinical and participant-reported outcomes. SRI-5 and SRI-6 are composite indices of SLE disease improvement that consist of scores derived from the SLEDAI-2K and the BILAG 2004 Index. The SRI-5 and SRI-6 are computed with a minimal five-point or six-point improvement in SLEDAI-2K being required, respectively.
Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast)	Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180	The PK of BOS161721 was characterized and the optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels	Baseline (Day 0); Day 210	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm)	Baseline (Day 0); Day 180	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.
Phase 2: Number of Participants With Medication Failures	Days 30, 60, 90, 120, 150, 180, and 210	Effect of BOS161721 compared with placebo for response on clinical indicators of SLE activity was assessed in adult participants with moderate to severe SLE on limited background standard of care treatment.
Phase 2: Time to First BILAG Flare (≥ 1 New or Recurrent BILAG A or > 1 New or Recurrent BILAG B) Relative to Baseline Through Day 210	Baseline; Day 210	The BILAG-2004 index is an organ-specific 97-question assessment based on the principle of the doctor's intent to treat. Only clinical features attributable to SLE disease activity were recorded and based on the participant's condition in the last 4 weeks compared with the previous 4 weeks. It was scored as not present (0), improved (1), the same (2), worse (3), or new (4). Disease activity was graded separately for 9 body systems to 5 different grades (A to E) as follows: A is very active disease, B is moderate activity, C is mild stable disease, D is inactive now but previously active, and E indicates the organ was never involved. A shift from BILAG-2004 Grade A or B to a lower grade indicates a clinically relevant change in disease activity as the BILAG-2004 grades mirror the decision points for treatment interventions.
Phase 2: Number of Participants With AEs	Up to Day 270	The safety and tolerability of repeat doses of BOS161721 (120 mg) administered SC were assessed in adult participants with moderate to severe SLE on limited background standard of care treatment.
Phase 1b: Maximum Observed Concentration (Cmax)	Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180	The PK of BOS161721 was characterized and the optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 1b: First Time to Maximum Concentration (Tmax)	Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180	The PK of BOS161721 was characterized and the optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit	Baseline (Day 0); Days 30, 60, 90, 120, 150, 180, 210, 240, and 270	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE..
Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB)	Baseline (Day 0); Day 180	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.
Phase 2: Number of Participants With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210	Day 210	The BICLA is a responder index developed to measure response to therapy, and it includes scores from the BILAG, SLEDAI-2K, and Physician's Global Assessment (PGA). BICLA response is defined as: 1) at least 1 gradation of improvement in baseline BILAG 2004 scores in all body systems with moderate disease activity at entry (eg, all B \[moderate disease\] scores falling to C \[mild\], or D \[no activity\]); 2) no new BILAG A or more than 1 new BILAG B scores; 3) no worsening of total SLEDAI-2K score from baseline; 4) ≤ 10% deterioration in PGA score; and 5) no treatment failure. The PGA is measured on a 0 to 100 mm scale with score 0 to be No Disease Activity and score 100 to be the most Severe Disease Activity.
Phase 2: Mean Change From Baseline in CLASI at Day 210	Baseline, Day 210	The CLASI is a comprehensive tool for the assessment of disease activity (CLASI-A) and damage (CLASI-B) in cutaneous lupus, shown to be valid, reliable, and sensitive to changes in disease activity. Response is defined as 50% improvement from baseline in "A" or "B" scores. This assessment was applied to all participants as all were required to have cutaneous disease activity. The total score represents the sum of the individual scores and ranges from 0 to 70 (CLASI-A) and 0 to 58 (CLASI-B). Higher scores are awarded for more severe manifestations. Change from baseline was calculated as the post-baseline value minus the baseline value.
Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210	Baseline, Day 210	The SLEDAI-2K is a validated instrument that measures disease activity in SLE participants at the time of the visit and in the previous 30 days. It is a global index and includes 24 clinical and laboratory variables that are weighted by the type of manifestation, but not by severity. The total score falls between 0 and 105, with higher scores representing increased disease activity. A SLEDAI -2K of 6 or more generally represents moderately to severely active disease. Change from baseline was calculated as the post-baseline value minus the baseline value.
Phase 1b: Mean Change From Baseline in Abrogation of IL-21 Gene Signature	Baseline (Day 0); Days 15, 90, 180, and 270	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 2: Number of Participants With a Sustained Reduction From Baseline of Oral Corticosteroid (CS) (≤ 7.5 mg/Day and < Day 0 Dose) Between Day 150 and Day 210	Day 150 to Day 210	Effect of BOS161721 compared with placebo for response on clinical indicators of SLE activity was assessed in adult participants with moderate to severe SLE on limited background standard of care treatment.
Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F)	Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180	The PK of BOS161721 was characterized and the optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype	Baseline (Day 0); Day 180	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.
Phase 2: Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210	Day 210	The CLASI is a comprehensive tool for assessment of disease activity (CLASI-A) in cutaneous lupus, shown to be valid, reliable, and sensitive to changes in disease activity. Response is defined as at least 50% improvement from baseline in "A" scores. This assessment was applied to all participants as all were required to have cutaneous disease activity. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.
Phase 2: Mean Change From Baseline in the Total Number of Swollen Joints, Tender Joints, and Active Joints (Swelling and Tenderness in the Same Joint) in the American College of Rheumatology-28 (ACR-28) Joint Count	Baseline, Day 210	The ACR-28 joint count evaluated the number of tender and swollen joints in the shoulder, elbow, wrist, hand, and knee joints. Joints of the feet were excluded. Change from baseline was calculated as the post-baseline value minus the baseline value.
Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index	Baseline; Day 180	The SLICC/ACR damage index is a validated instrument to assess damage, defined as irreversible impairment, continuously persistent for 6 months (ascertained by clinical assessment), occurring since the onset of lupus, and it is based on a weighted scoring system. This index records damage occurring in participants with SLE regardless of cause, with demonstrated content, face, criterion, and discriminant validity. A score of 0=no damage. Total maximum score is 47 and increasing score indicates increasing disease severity.
Mean Percent Change in CS Administration From the Baseline Day 0 Dose Through Day 210 in Participants Receiving ≥ 7.5 mg/Day Prednisone Equivalent at Day 0	Baseline; Day 210	The percent reduction in CS administration from Day 0 through Day 210 was determined based on the average daily CS usage.
Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210	Days 30, 60, 90, 120, 150, 180, 210	The BILAG-2004 index is an organ-specific 97-question assessment based on the principle of the doctor's intent to treat. Only clinical features attributable to SLE disease activity were recorded and based on the participant's condition in the last 4 weeks compared with the previous 4 weeks. It was scored as not present (0), improved (1), the same (2), worse (3), or new (4). Disease activity was graded separately for 9 body systems to 5 different grades (A to E) as follows: A is very active disease, B is moderate activity, C is mild stable disease, D is inactive now but previously active, and E indicates the organ was never involved. A shift from BILAG-2004 Grade A or B to a lower grade indicates a clinically relevant change in disease activity as the BILAG-2004 grades mirror the decision points for treatment interventions.
Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening	Days 30, 60, 90, 120, 150, 180, and 210	The PGA is used to assess Investigator's general impression on the patient's overall status of SLE disease activity via visual analogue scale (100 mm) with 0 being "very good, asymptomatic and no limitation of normal activities" with 100 mm being "most severe possible disease ever seen in all SLE patients". PGA worsening is defined as an increase of ≥ 30 mm from baseline.
Phase 2: Time to Medication Failure	Up to Day 270	Participants who received prohibited medications or undergo unallowable corticosteroid (CS) usage were considered "medication failures".
Phase 2: Duration of Longest SRI-4 Response	Up to Day 270	The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from SLEDAI-2K, BILAG 2004 Index and PGA. Response based on the SRI-4 is defined by: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B) compare with baseline; and 3) no deterioration from baseline in the PGA by ≥ 30 millimeters. The total SLEDAI-2K score falls between 0 and 105, with higher scores representing increased disease activity. The PGA is used to assess Investigator's general impression on the patient's overall status of SLE disease activity via visual analogue scale (100 mm) with 0 being "very good, asymptomatic and no limitation of normal activities" with 100 mm being "most severe possible disease ever seen in all SLE patients". The SRI-4 response in participants with moderate to severe SLE is associated with broad improvements in clinical and participant-reported outcomes.

Trial Locations

Locations (67): Hospital Militar Central - Servicio de Reumatología
🇦🇷
Ciudad Autonoma de Buenos Aires, Argentina
Centro Medico Privado de Reumatologia
🇦🇷
San Miguel De Tucumán, Argentina
Centro de Investigaciones Reumatologicas
🇦🇷
San Miguel De Tucumán, Argentina
University Multiprofile Hospital for Active Treatment Plovdiv
🇧🇬
Plovdiv, Bulgaria
Centro Integral de Reumatologia del Caribe CIRCARIBE S.A.S
🇨🇴
Barranquilla, Colombia
DE Klinikai Központ
🇭🇺
Debrecen, Hungary
Southern Philippines Medical Center
🇵🇭
Davao City, Philippines
Mary Mediatrix Medical Center
🇵🇭
Lipa City, Philippines
Reumatika-Centrum Reumatologii
🇵🇱
Warszawa, Poland
Centre for Rheumatology Immunology and Arthritis
🇺🇸
Fort Lauderdale, Florida, United States
Clinic of Robert Hozman/Clinical Investigation Specialists, Inc.
🇺🇸
Skokie, Illinois, United States
June DO PC
🇺🇸
Lansing, Michigan, United States
Accurate Clinical Research Inc
🇺🇸
Houston, Texas, United States
Medicity S.A.S.
🇨🇴
Bucaramanga, Colombia
Servimed S.A.S.
🇨🇴
Bucaramanga, Colombia
Philippine General Hospital
🇵🇭
Manila, Philippines
Centrum Kliniczno - Badawcze J. Brzezicki, B. Gronkiewicz Brzezicka Spółka Lekarska
🇵🇱
Elbląg, Poland
Clinical Research of West Florida
🇺🇸
Tampa, Florida, United States
Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States
Pinnacle Research Group
🇺🇸
Anniston, Alabama, United States
TriWest Research Associates
🇺🇸
El Cajon, California, United States
Valerius Medical Group and Research Center
🇺🇸
Los Alamitos, California, United States
Omega Research Consultants
🇺🇸
DeBary, Florida, United States
Westlake Medical Research
🇺🇸
Thousand Oaks, California, United States
Millennium Research
🇺🇸
Ormond Beach, Florida, United States
Aa Mrc Llc
🇺🇸
Grand Blanc, Michigan, United States
The Arthritis Center
🇺🇸
Palm Harbor, Florida, United States
Diagnostic Consultative Center Sveti Georgi EOOD
🇧🇬
Plovdiv, Bulgaria
Joint and Muscle Research Institute
🇺🇸
Charlotte, North Carolina, United States
Ramesh C. Gupta M.D.
🇺🇸
Memphis, Tennessee, United States
Framingham Centro Medico
🇦🇷
La Plata, Argentina
Medical Center - 1 - Sevlievo EOOD
🇧🇬
Sevlievo, Bulgaria
Preventive Care S.A.S.
🇨🇴
Bogota, Colombia
Hospital Pablo Tobon Uribe
🇨🇴
Medellín, Colombia
Research Institute of Clinical Medicine Ltd
🇬🇪
Tbilisi, Georgia
Clinica de Artritis Temprana
🇨🇴
Cali, Colombia
V. Tsitlanadze Scientifically-Practical Rheumatology Center Ltd
🇬🇪
Tbilisi, Georgia
LTD New Hospitals
🇬🇪
Tbilisi, Georgia
Mtskheta Street Clinic Ltd
🇬🇪
Tbilisi, Georgia
Multiprofile Clinic Consilium Medulla Ltd
🇬🇪
Tbilisi, Georgia
First Medical Center
🇬🇪
Tbilisi, Georgia
Qualiclinic Kft.
🇭🇺
Budapest, Hungary
Békés Megyei Központi Kórház Pándy Kálmán Tagkórház
🇭🇺
Gyula, Hungary
Centro Integral en Reumatología S.A. de C.V. (CIRSA)
🇲🇽
Guadalajara, Mexico
Hospital Civil de Guadalajara Fray Antonio Alcalde
🇲🇽
Guadalajara, Mexico
CLIDITER S.A. de C.V. (Centro de Investigación y Tratamiento de las Enfermedades Reumaticas)
🇲🇽
Mexico City, Mexico
Angeles University Foundation Medical Center
🇵🇭
Angeles City, Philippines
Hogar Clinica San Juan De Dios
🇵🇪
Cayma, Peru
Centro de Investigación Clínica Trujillo E.I.R.L.
🇵🇪
La Libertad, Peru
Hospital Nacional Cayetano Heredia
🇵🇪
Lima, Peru
Instituto de Ginecología y Reproducción
🇵🇪
Santiago De Surco, Peru
Clinica San Juan Bautista
🇵🇪
Lima, Peru
University of Santo Tomas Hospital
🇵🇭
Manila, Philippines
Centrum Medyczne Plejady
🇵🇱
Kraków, Poland
NZOZ Lecznica MAK-MED
🇵🇱
Nadarzyn, Poland
Centrum Nowoczesnych Terapii Dobry Lekarz sp. z o.o
🇵🇱
Kraków, Poland
Prywatna Praktyka Lekarska Prof. UM dr hab. med Pawel Hrycaj
🇵🇱
Poznań, Poland
SANUS Szpital Specjalistyczny sp. z o.o
🇵🇱
Stalowa Wola, Poland
Centrum Medyczne AMED oddział w Łodzi
🇵🇱
Łódź, Poland
Spitalul Clinic Judetean De Urgenta Cluj Napoca
🇷🇴
Cluj-Napoca, Romania
Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL
🇷🇴
Braşov, Romania
Spitalul Clinic de Recuperare Iasi #2
🇷🇴
Iaşi, Romania
National Scientific Center at Institute of Cardiology named after acad. M.D. Strazhesko
🇺🇦
Kyiv, Ukraine
Kyiv Regional Clinical Hospital
🇺🇦
Kyiv, Ukraine
Odesa Regional Clinical Hospital
🇺🇦
Odesa, Ukraine
Vinnytsia Regional Clinical Hospital
🇺🇦
Vinnytsia, Ukraine
Communal Non-Profit Enterprise "Ternopil University Clinic" of Ternopil Regional Council
🇺🇦
Ternopil, Ukraine