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

Systemic Lupus Erythematosus Clinical Trial

Official title:

A Randomized Double-Blind Phase 1b/2 Combined Staggered Multiple Dose Escalation Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03371251
• Other study ID #: BOS161721-02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 10, 2018
• Est. completion date: November 26, 2020

Study information

• Verified date: February 2022
• Source: Boston Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: November 26, 2020
• Est. primary completion date: November 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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:

1. 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

2. If AZA, myocophenolate mofetil, mycophenolic acid, hydroxychloroquine, or MTX were discontinued prior to screening, the washout period must be = 12 weeks.

3. 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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• BOS161721
SC administration
• Placebo
SC administration

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boston Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Colombia,  Georgia,  Hungary,  Mexico,  Peru,  Philippines,  Poland,  Romania,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Number of Participants With Adverse Events (AEs)	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.	Up to Day 270
Primary	Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at 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.	Day 210
Secondary	Phase 1b: Maximum Observed Concentration (Cmax)	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.	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
Secondary	Phase 1b: First Time to Maximum Concentration (Tmax)	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.	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
Secondary	Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast)	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.	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
Secondary	Phase 1b: Terminal Elimination Half-life (t1/2)	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.	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
Secondary	Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F)	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.	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
Secondary	Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F)	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.	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
Secondary	Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3)	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and pharmacodynamic (PD) data in participants with moderate to severe SLE.	Baseline (Day 0); Days 30, 44, 60, and 90 (pre-dose [trough] samples only)
Secondary	Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.	Baseline (Day 0); Day 210
Secondary	Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.	Baseline (Day 0); Day 180
Secondary	Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE..	Baseline (Day 0); Days 30, 60, 90, 120, 150, 180, 210, 240, and 270
Secondary	Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB)	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.	Baseline (Day 0); Day 180
Secondary	Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm)	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.	Baseline (Day 0); Day 180
Secondary	Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG)	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.	Baseline (Day 0); Day 180
Secondary	Phase 1b: Mean Change From Baseline in Abrogation of IL-21 Gene Signature	The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.	Baseline (Day 0); Days 15, 90, 180, and 270
Secondary	Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit	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.	Days 30, 60, 90, 120, 150, 180, 210, 240, and 270
Secondary	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	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.	Day 150 to Day 210
Secondary	Phase 2: Number of Participants With New or Recurrent BILAG Flares (= 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through 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.	Days 30, 60, 90, 120, 150, 180, 210
Secondary	Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening	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.	Days 30, 60, 90, 120, 150, 180, and 210
Secondary	Phase 2: Number of Participants With a BILAG-based Composite Lupus Assessment (BICLA) Response at 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.	Day 210
Secondary	Phase 2: Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at 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.	Day 210
Secondary	Phase 2: Number of Participants With Medication Failures	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.	Days 30, 60, 90, 120, 150, 180, and 210
Secondary	Phase 2: Mean Change From Baseline in CLASI at 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.	Baseline, Day 210
Secondary	Phase 2: Mean Change From Baseline in PGA	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".	Baseline, Day 210
Secondary	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	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.	Baseline, Day 210
Secondary	Phase 2: Mean Change From Baseline in SLEDAI-2K at 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.	Baseline, Day 210
Secondary	Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index	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.	Baseline; Day 180
Secondary	Phase 2: Time to Medication Failure	Participants who received prohibited medications or undergo unallowable corticosteroid (CS) usage were considered "medication failures".	Up to Day 270
Secondary	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	The percent reduction in CS administration from Day 0 through Day 210 was determined based on the average daily CS usage.	Baseline; Day 210
Secondary	Phase 2: Duration of Longest SRI-4 Response	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.	Up to Day 270
Secondary	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	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.	Baseline; Day 210
Secondary	Phase 2: Number of Participants With AEs	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.	Up to Day 270