Systemic Lupus Erythematosus
Conditions
Keywords
Adults, BOS161721, standard of care, moderately to severely active Systemic Lupus Erythematosus
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.
Interventions
DRUGBOS161721
SC administration
DRUGPlacebo
SC administration
Sponsors
Boston Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: 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: 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 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 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 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 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 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 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 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: 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 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: 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: 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: 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: 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 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 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 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 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. |
| 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. |
| 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: 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. |
| 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 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 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. |
Countries
Argentina, Bulgaria, Colombia, Georgia, Hungary, Mexico, Peru, Philippines, Poland, Romania, Ukraine, United States
Participant flow
Recruitment details
The study was conducted in in the United States, Georgia, Bulgaria, Hungary, Poland, Argentina, Columbia, Mexico, Romania, Ukraine, Philippines and Peru. The first participant was screened on 10 January 2018 and last participant last visit occurred on 26, November 2020.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b: Placebo Participants were randomized to receive a subcutaneous (SC) dose of placebo. Participants received 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 at Days 210, 240, and 270. | 7 |
| Phase 1b: Cohort 1: BOS161721 20 mg Participants were randomized to receive a 20 mg SC dose of BOS161721. Participants received 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. | 5 |
| Phase 1b: Cohort 2: BOS161721 60 mg Participants were randomized to receive a 60 mg SC dose of BOS161721. Participants received 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 | 9 |
| Phase 1b: Cohort 3: BOS161721 120 mg Participants were randomized to receive a 120 mg SC dose of BOS161721. Participants received 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 | 9 |
| Phase 2: Placebo Participants were randomized to receive a SC dose of placebo (as determined from Phase 1b of the study). Participants received 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. | 37 |
| Phase 2: BOS161721 120 mg Participants were randomized to receive a 120 mg SC dose of BOS161721 (as determined from Phase 1b of the study). Participants received 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. | 76 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Decision by Sponsor | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Phase 1b: Pregnancy, Phase 2: fear of COVID-19 or local restrictions | 1 | 0 | 0 | 0 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Cohort 3: BOS161721 120 mg | Phase 2: BOS161721 120 mg | Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Placebo | Phase 1b: Placebo |
|---|---|---|---|---|---|---|---|
| Age, Continuous BOS161721 | 45.5 years STANDARD_DEVIATION 12.07 | 49.3 years STANDARD_DEVIATION 11.31 | 47.3 years STANDARD_DEVIATION 10.43 | 44.5 years STANDARD_DEVIATION 12.52 | 50.0 years STANDARD_DEVIATION 8.51 | — | — |
| Age, Continuous Placebo | 46.1 years STANDARD_DEVIATION 13.25 | — | — | — | — | 45.7 years STANDARD_DEVIATION 12.52 | 48.1 years STANDARD_DEVIATION 17.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 53 Participants | 2 Participants | 0 Participants | 32 Participants | 1 Participants | 17 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants | 7 Participants | 9 Participants | 44 Participants | 4 Participants | 20 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 0 Participants | 3 Participants | 7 Participants | 0 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 35 Participants | 0 Participants | 0 Participants | 24 Participants | 0 Participants | 11 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 9 Participants | 6 Participants | 45 Participants | 5 Participants | 20 Participants | 5 Participants |
| Sex: Female, Male Female | 133 Participants | 8 Participants | 8 Participants | 69 Participants | 5 Participants | 36 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 1 Participants | 1 Participants | 7 Participants | 0 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 5 | 0 / 9 | 0 / 9 | 0 / 37 | 0 / 76 |
| other Total, other adverse events | 4 / 7 | 2 / 5 | 7 / 9 | 8 / 9 | 22 / 37 | 44 / 76 |
| serious Total, serious adverse events | 1 / 7 | 0 / 5 | 2 / 9 | 0 / 9 | 3 / 37 | 2 / 76 |
Outcome results
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.
Time frame: Up to Day 270
Population: Safety Analysis Set (SS): Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least one evaluable post-baseline safety evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 2 or Higher TEAE | 1 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Injection Site Reaction | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 3 or Higher TEAE | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 3 TEAE | 1 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Resulting in Death | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Serious TEAE | 1 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent Adverse Events (TEAE) | 4 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE of Special Interest | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Serious TEAE | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Resulting in Death | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE of Special Interest | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or Higher TEAE | 4 Participants |
| Phase 1b: Placebo | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE | 1 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Serious TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent Adverse Events (TEAE) | 2 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Serious TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or Higher TEAE | 2 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 2 or Higher TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 3 TEAE | 1 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 3 or Higher TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE of Special Interest | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE of Special Interest | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Injection Site Reaction | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE of Special Interest | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent Adverse Events (TEAE) | 7 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE | 1 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 3 TEAE | 2 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Serious TEAE | 2 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 2 or Higher TEAE | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE of Special Interest | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 3 or Higher TEAE | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Serious TEAE | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Injection Site Reaction | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or Higher TEAE | 6 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Serious TEAE | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Treatment-Emergent Adverse Events (TEAE) | 8 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | TEAE of Special Interest | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Serious TEAE | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE of Special Interest | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Related Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 2 or Higher TEAE | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any CTCAE Grade 3 TEAE | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Injection Site Reaction | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Related CTCAE Grade 3 or Higher TEAE | 0 Participants |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Number of Participants With Adverse Events (AEs) | Any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or Higher TEAE | 7 Participants |
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.
Time frame: Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post-baseline efficacy evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | SRI-4 Response | 19 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | ≥ 4-Point Reduction from Baseline in SLEDAI-2K Global Score | 19 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | No New BILAG A or More than One BILAG B Organ Score Compared with Baseline | 27 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | No Deterioration from Baseline in PGA by >=30mm | 27 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | No Deterioration from Baseline in PGA by >=30mm | 68 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | SRI-4 Response | 40 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | No New BILAG A or More than One BILAG B Organ Score Compared with Baseline | 68 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 | ≥ 4-Point Reduction from Baseline in SLEDAI-2K Global Score | 40 Participants |
Comparison: Statistical Analysis: SRI-4 Responsep-value: 0.843490% CI: [-14.5, 18.5]Pearson's chi-square test
Comparison: Statistical Analysis: \>= 4-Point Reduction from Baseline in SLEDAI-2K Global Scorep-value: 0.843490% CI: [-14.5, 18.5]Pearson's chi-square test
Comparison: Statistical Analysis: No New BILAG A or More than One BILAG B Organ Score Compared with Baselinep-value: 0.014190% CI: [4.5, 30.9]Pearson's chi-square test
Comparison: Statistical Analysis: No Deterioration from Baseline in PGA by \>=30mmp-value: 0.014190% CI: [4.5, 30.9]Pearson's chi-square test
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.
Time frame: Baseline; Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Participants in the Full Analysis Set who received \>= 7.5 mg/day prednisone equivalent at Day 0 were included. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | 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 | -36.61 Percent Reduction in Dose (mg/day) | Standard Deviation 22.389 |
| Phase 1b: Cohort 1: BOS161721 20 mg | 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 | -21.49 Percent Reduction in Dose (mg/day) | Standard Deviation 26.95 |
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.
Time frame: 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
Population: The PK population is defined as all participants who received at least 1 dose (partial or complete) of study treatment and had sufficient concentration data for the calculation of PK parameters. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F) | 0.289 Liter/day | Geometric Coefficient of Variation 18.3 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F) | 0.311 Liter/day | Geometric Coefficient of Variation 179 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F) | 0.218 Liter/day | Geometric Coefficient of Variation 38.8 |
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.
Time frame: 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
Population: The PK population is defined as all participants who received at least 1 dose (partial or complete) of study treatment and had sufficient concentration data for the calculation of PK parameters. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F) | 31.4 Liter | Geometric Coefficient of Variation 33.2 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F) | 18.5 Liter | Geometric Coefficient of Variation 39.6 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F) | 23.0 Liter | — |
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.
Time frame: 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
Population: The PK population is defined as all participants who received at least 1 dose (partial or complete) of study treatment and had sufficient concentration data for the calculation of PK parameters. Here, number analyzed in each row signifies only the participants with available data for each dose.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 2 | 1.04 Day |
| Phase 1b: Placebo | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 1 | 7.01 Day |
| Phase 1b: Placebo | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 7 | 6.18 Day |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 2 | 1.00 Day |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 1 | 7.00 Day |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 7 | 3.55 Day |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 1 | 8.04 Day |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 7 | 8.96 Day |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: First Time to Maximum Concentration (Tmax) | Dose 2 | 1.00 Day |
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.
Time frame: 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
Population: The PK population is defined as all participants who received at least 1 dose (partial or complete) of study treatment and had sufficient concentration data for the calculation of PK parameters. Here, number analyzed in each row signifies only the participants with available data for each dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 2 | 1240 ng/mL | Geometric Coefficient of Variation 23.9 |
| Phase 1b: Placebo | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 1 | 1160 ng/mL | Geometric Coefficient of Variation 42 |
| Phase 1b: Placebo | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 7 | 2580 ng/mL | Geometric Coefficient of Variation 19.1 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 2 | 5670 ng/mL | Geometric Coefficient of Variation 35.7 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 1 | 4610 ng/mL | Geometric Coefficient of Variation 54.8 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 7 | 7820 ng/mL | Geometric Coefficient of Variation 144 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 1 | 5500 ng/mL | Geometric Coefficient of Variation 52.3 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 7 | 20300 ng/mL | Geometric Coefficient of Variation 37.1 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Maximum Observed Concentration (Cmax) | Dose 2 | 7580 ng/mL | Geometric Coefficient of Variation 45.1 |
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.
Time frame: Baseline (Day 0); Days 15, 90, 180, and 270
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and have at least 1 evaluable post baseline efficacy evaluation. Data were not collected for this outcome measure.
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..
Time frame: Baseline (Day 0); Days 30, 60, 90, 120, 150, 180, 210, 240, and 270
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, number analyzed in each row signifies only the participants with available data for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 210 | 0.05 International units per millilitre | Standard Deviation 0.359 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 30 | -1.11 International units per millilitre | Standard Deviation 3.504 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 180 | -2.13 International units per millilitre | Standard Deviation 5.905 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 120 | -0.02 International units per millilitre | Standard Deviation 0.27 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 270 | -1.94 International units per millilitre | Standard Deviation 4.974 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 90 | 0.15 International units per millilitre | Standard Deviation 0.448 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 240 | 0.07 International units per millilitre | Standard Deviation 0.428 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 150 | -0.03 International units per millilitre | Standard Deviation 0.199 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 60 | -1.81 International units per millilitre | Standard Deviation 5.048 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 150 | 0.62 International units per millilitre | Standard Deviation 0.709 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 210 | 0.07 International units per millilitre | Standard Deviation 0.54 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 180 | 0.52 International units per millilitre | Standard Deviation 0.584 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 60 | 0.40 International units per millilitre | Standard Deviation 0.376 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 270 | 0.37 International units per millilitre | Standard Deviation 0.7 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 90 | 0.00 International units per millilitre | Standard Deviation 0.187 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 240 | 0.34 International units per millilitre | Standard Deviation 1.117 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 120 | 0.41 International units per millilitre | Standard Deviation 0.598 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 30 | 0.48 International units per millilitre | Standard Deviation 0.41 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 30 | 5.34 International units per millilitre | Standard Deviation 9.053 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 60 | 8.06 International units per millilitre | Standard Deviation 18.43 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 90 | 19.31 International units per millilitre | Standard Deviation 48.594 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 120 | 12.30 International units per millilitre | Standard Deviation 35.583 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 150 | 17.39 International units per millilitre | Standard Deviation 50.086 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 180 | 8.00 International units per millilitre | Standard Deviation 21.169 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 210 | 6.76 International units per millilitre | Standard Deviation 20.173 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 240 | 6.81 International units per millilitre | Standard Deviation 21.903 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 270 | 7.99 International units per millilitre | Standard Deviation 24.116 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 210 | -17.96 International units per millilitre | Standard Deviation 50.274 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 120 | -15.58 International units per millilitre | Standard Deviation 47.248 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 90 | -13.44 International units per millilitre | Standard Deviation 35.152 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 270 | -9.71 International units per millilitre | Standard Deviation 27.833 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 240 | -18.35 International units per millilitre | Standard Deviation 47.898 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 60 | -6.11 International units per millilitre | Standard Deviation 15.612 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 180 | -17.13 International units per millilitre | Standard Deviation 49.897 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 150 | -11.18 International units per millilitre | Standard Deviation 38.152 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit | Day 30 | -11.51 International units per millilitre | Standard Deviation 32.444 |
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.
Time frame: Baseline (Day 0); Day 180
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and have at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Anti-Cardiolipin IgG Antibody | -0.03 U/mL | Standard Deviation 0.412 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Beta-2 Glycoprotein 1 IgG Antibody | -0.11 U/mL | Standard Deviation 0.358 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Beta-2 Glycoprotein 1 IgG Antibody | -7.48 U/mL | Standard Deviation 23.684 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Anti-Cardiolipin IgG Antibody | 3.55 U/mL | Standard Deviation 5.559 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Anti-Cardiolipin IgG Antibody | 0.07 U/mL | Standard Deviation 0.585 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Beta-2 Glycoprotein 1 IgG Antibody | -0.14 U/mL | Standard Deviation 0.882 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Anti-Cardiolipin IgG Antibody | -0.42 U/mL | Standard Deviation 0.18 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) | Beta-2 Glycoprotein 1 IgG Antibody | 0.02 U/mL | Standard Deviation 0.787 |
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.
Time frame: Baseline (Day 0); Day 180
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and have at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A60 Antibody | 0.00 U/mL | Standard Deviation 0 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A52 Antibody | -0.04 U/mL | Standard Deviation 0.128 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | La Antibody | 0.04 U/mL | Standard Deviation 0.175 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A60 Antibody | 0.00 U/mL | Standard Deviation 0 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | La Antibody | 0.11 U/mL | Standard Deviation 0.108 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A52 Antibody | 0.05 U/mL | Standard Deviation 0.112 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | La Antibody | 1.02 U/mL | Standard Deviation 2.639 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A60 Antibody | -2.62 U/mL | Standard Deviation 7.867 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A52 Antibody | 0.19 U/mL | Standard Deviation 0.567 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A52 Antibody | -2.25 U/mL | Standard Deviation 4.861 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | Sjogrens SS-A60 Antibody | -4.36 U/mL | Standard Deviation 8.684 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) | La Antibody | 0.47 U/mL | Standard Deviation 1.668 |
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.
Time frame: Baseline (Day 0); Day 180
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and have at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm) | -1.87 U/mL | Standard Deviation 4.827 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm) | 0.74 U/mL | Standard Deviation 0.391 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm) | -3.21 U/mL | Standard Deviation 9.419 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm) | 3.61 U/mL | Standard Deviation 19.504 |
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.
Time frame: Baseline (Day 0); Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, number analyzed in each row signifies only the participants with available data for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C3, Day 210 | 0.094 gram/Litre | Standard Deviation 0.2289 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C4, Day 210 | 0.024 gram/Litre | Standard Deviation 0.0391 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C4, Day 210 | -0.038 gram/Litre | Standard Deviation 0.037 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C3, Day 210 | -0.032 gram/Litre | Standard Deviation 0.0876 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C3, Day 210 | 0.050 gram/Litre | Standard Deviation 0.3424 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C4, Day 210 | -0.007 gram/Litre | Standard Deviation 0.0783 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C3, Day 210 | -0.078 gram/Litre | Standard Deviation 0.2879 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels | C4, Day 210 | -0.024 gram/Litre | Standard Deviation 0.041 |
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.
Time frame: Baseline (Day 0); Day 180
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+% of CD19+ | -0.21 Change in percentage of cells | Standard Deviation 3.866 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD4+CD8-% of CD3+ | -1.01 Change in percentage of cells | Standard Deviation 10.866 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138+% of CD19+ | 0.03 Change in percentage of cells | Standard Deviation 0.049 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD4+CD8- | 0.81 Change in percentage of cells | Standard Deviation 12.373 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138-% of CD19+ | -0.20 Change in percentage of cells | Standard Deviation 0.432 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD25+CD127- | 0.31 Change in percentage of cells | Standard Deviation 6.093 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27-% of CD19+ | -1.29 Change in percentage of cells | Standard Deviation 2.963 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD25+CD127- | 8.59 Change in percentage of cells | Standard Deviation 10.618 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD56+% OF CD45+ Lymphocytes | -0.56 Change in percentage of cells | Standard Deviation 2.093 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD25+CD127-% of CD4+CD8- | -1.03 Change in percentage of cells | Standard Deviation 1.388 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD4+CD8- | 3.93 Change in percentage of cells | Standard Deviation 6.906 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+C27-% of CD19+ | 0.20 Change in percentage of cells | Standard Deviation 7.127 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD25+CD127- | 0.20 Change in percentage of cells | Standard Deviation 4.676 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD19+% of CD45+ Lymphocytes | -2.07 Change in percentage of cells | Standard Deviation 3.201 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27+% of CD19+ | 1.29 Change in percentage of cells | Standard Deviation 1.785 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27-CD38++CD24++% of CD19+ | 0.50 Change in percentage of cells | Standard Deviation 1.262 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD8+CD4-% of CD3+ | -3.00 Change in percentage of cells | Standard Deviation 7.792 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD4+CD8- | -0.07 Change in percentage of cells | Standard Deviation 6.366 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27-CD38++CD24++% of CD19+ | 0.56 Change in percentage of cells | Standard Deviation 1.688 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27+% of CD19+ | -3.24 Change in percentage of cells | Standard Deviation 6.08 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD56+% OF CD45+ Lymphocytes | -5.76 Change in percentage of cells | Standard Deviation 4.231 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD4+CD8- | 0.14 Change in percentage of cells | Standard Deviation 5.227 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138+% of CD19+ | 0.04 Change in percentage of cells | Standard Deviation 0.089 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD4+CD8-% of CD3+ | -3.08 Change in percentage of cells | Standard Deviation 5.272 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD25+CD127- | 3.30 Change in percentage of cells | Standard Deviation 5.039 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD19+% of CD45+ Lymphocytes | -5.34 Change in percentage of cells | Standard Deviation 4.663 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138-% of CD19+ | -0.20 Change in percentage of cells | Standard Deviation 0.354 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD4+CD8- | 15.18 Change in percentage of cells | Standard Deviation 7.564 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD25+CD127- | 7.02 Change in percentage of cells | Standard Deviation 3.371 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+C27-% of CD19+ | 2.42 Change in percentage of cells | Standard Deviation 5.882 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27-% of CD19+ | 1.36 Change in percentage of cells | Standard Deviation 2.373 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD8+CD4-% of CD3+ | -1.38 Change in percentage of cells | Standard Deviation 4.467 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD25+CD127-% of CD4+CD8- | -0.22 Change in percentage of cells | Standard Deviation 2.406 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD4+CD8- | 4.14 Change in percentage of cells | Standard Deviation 4.146 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD25+CD127- | 1.56 Change in percentage of cells | Standard Deviation 3.84 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+% of CD19+ | -0.48 Change in percentage of cells | Standard Deviation 3.891 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD25+CD127- | 7.41 Change in percentage of cells | Standard Deviation 6.064 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD56+% OF CD45+ Lymphocytes | -2.38 Change in percentage of cells | Standard Deviation 2.461 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD8+CD4-% of CD3+ | -2.92 Change in percentage of cells | Standard Deviation 5.01 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD25+CD127- | 10.62 Change in percentage of cells | Standard Deviation 11.963 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD4+CD8- | 13.14 Change in percentage of cells | Standard Deviation 16.091 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD25+CD127- | 12.93 Change in percentage of cells | Standard Deviation 11.905 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD4+CD8- | 5.01 Change in percentage of cells | Standard Deviation 5.053 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+C27-% of CD19+ | -1.07 Change in percentage of cells | Standard Deviation 4.748 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27+% of CD19+ | -1.24 Change in percentage of cells | Standard Deviation 2.823 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27-CD38++CD24++% of CD19+ | -0.42 Change in percentage of cells | Standard Deviation 2.351 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+% of CD19+ | 2.02 Change in percentage of cells | Standard Deviation 3.751 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138+% of CD19+ | 0.08 Change in percentage of cells | Standard Deviation 0.172 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138-% of CD19+ | 0.59 Change in percentage of cells | Standard Deviation 1.437 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27-% of CD19+ | 0.32 Change in percentage of cells | Standard Deviation 2.059 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD4+CD8- | 6.39 Change in percentage of cells | Standard Deviation 5.882 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD19+% of CD45+ Lymphocytes | -0.39 Change in percentage of cells | Standard Deviation 4.201 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD25+CD127-% of CD4+CD8- | -0.38 Change in percentage of cells | Standard Deviation 1.495 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD4+CD8-% of CD3+ | 0.88 Change in percentage of cells | Standard Deviation 7.434 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD25+CD127- | -8.49 Change in percentage of cells | Standard Deviation 13.258 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27-CD38++CD24++% of CD19+ | 0.16 Change in percentage of cells | Standard Deviation 1.385 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+CD27+% of CD19+ | 1.00 Change in percentage of cells | Standard Deviation 3.26 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD8+CD4-% of CD3+ | -0.24 Change in percentage of cells | Standard Deviation 6.517 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | PD-1+% of CD4+CD8- | -9.01 Change in percentage of cells | Standard Deviation 13.036 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD+C27-% of CD19+ | -0.80 Change in percentage of cells | Standard Deviation 6.031 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD4+CD8- | 0.54 Change in percentage of cells | Standard Deviation 15.534 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD56+% OF CD45+ Lymphocytes | 2.04 Change in percentage of cells | Standard Deviation 7.984 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD19+% of CD45+ Lymphocytes | 0.27 Change in percentage of cells | Standard Deviation 3.481 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | ICOS+% of CD25+CD127- | 4.27 Change in percentage of cells | Standard Deviation 17.059 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD4+CD8- | -0.69 Change in percentage of cells | Standard Deviation 7.208 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD4+CD8-% of CD3+ | -5.04 Change in percentage of cells | Standard Deviation 7.671 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CD25+CD127-% of CD4+CD8- | -1.08 Change in percentage of cells | Standard Deviation 2.266 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | CXCR5+% of CD25+CD127- | 0.63 Change in percentage of cells | Standard Deviation 5.915 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27-% of CD19+ | -0.83 Change in percentage of cells | Standard Deviation 1.648 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138-% of CD19+ | -0.63 Change in percentage of cells | Standard Deviation 1.081 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+CD38++CD138+% of CD19+ | -0.02 Change in percentage of cells | Standard Deviation 0.13 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype | IgD-CD27+% of CD19+ | 0.70 Change in percentage of cells | Standard Deviation 3.74 |
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.
Time frame: Baseline (Day 0); Days 30, 44, 60, and 90 (pre-dose [trough] samples only)
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, number analyzed in each row signifies only the participants with available data for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 30 | 12.72 Percentage | Standard Deviation 25.172 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 44 | 18.45 Percentage | Standard Deviation 24.025 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 60 | -1.48 Percentage | Standard Deviation 19.129 |
| Phase 1b: Placebo | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 90 | -15.94 Percentage | Standard Deviation 34.757 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 44 | -60.00 Percentage | Standard Deviation 19.672 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 60 | -59.46 Percentage | Standard Deviation 20.31 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 90 | -67.48 Percentage | Standard Deviation 15.63 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 30 | -41.80 Percentage | Standard Deviation 24.631 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 60 | -32.68 Percentage | Standard Deviation 19.214 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 44 | -32.99 Percentage | Standard Deviation 19.899 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 90 | -33.03 Percentage | Standard Deviation 19.637 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 30 | -31.35 Percentage | Standard Deviation 20.281 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 90 | -26.74 Percentage | Standard Deviation 20.962 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 44 | -26.57 Percentage | Standard Deviation 20.856 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 30 | -25.73 Percentage | Standard Deviation 20.895 |
| Phase 1b: Cohort 3: BOS161721 120 mg | Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) | % pSTAT3+ Lymphocytes - Stimulated, Day 60 | -25.91 Percentage | Standard Deviation 20.85 |
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.
Time frame: 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
Population: The PK population is defined as all participants who received at least 1 dose (partial or complete) of study treatment and had sufficient concentration data for the calculation of PK parameters. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: Terminal Elimination Half-life (t1/2) | 75.2 Day | Geometric Coefficient of Variation 19.9 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: Terminal Elimination Half-life (t1/2) | 66.3 Day | Geometric Coefficient of Variation 35.4 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: Terminal Elimination Half-life (t1/2) | 64.3 Day | — |
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.
Time frame: 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
Population: The PK population is defined as all participants who received at least 1 dose (partial or complete) of study treatment and had sufficient concentration data for the calculation of PK parameters. Here, number analyzed in each row signifies only the participants with available data for each dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 1 | 25100 day*ng/mL | Geometric Coefficient of Variation 40.4 |
| Phase 1b: Placebo | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 2 | 33600 day*ng/mL | Geometric Coefficient of Variation 18.2 |
| Phase 1b: Placebo | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 7 | 155000 day*ng/mL | Geometric Coefficient of Variation 17.9 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 1 | 89400 day*ng/mL | Geometric Coefficient of Variation 51.7 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 7 | 460000 day*ng/mL | Geometric Coefficient of Variation 173 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 2 | 147000 day*ng/mL | Geometric Coefficient of Variation 29.7 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 7 | 1400000 day*ng/mL | Geometric Coefficient of Variation 38.7 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 2 | 229000 day*ng/mL | Geometric Coefficient of Variation 47.9 |
| Phase 1b: Cohort 2: BOS161721 60 mg | Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 1 | 124000 day*ng/mL | Geometric Coefficient of Variation 40.5 |
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.
Time frame: Up to Day 270
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Duration of Longest SRI-4 Response | 119.8 Days | Standard Deviation 68.26 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Duration of Longest SRI-4 Response | 124.2 Days | Standard Deviation 68.48 |
p-value: 0.789890% CI: [-22.92, 31.7]ANOVA
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.
Time frame: Baseline, Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Mean Change From Baseline in CLASI at Day 210 | CLASI-A (Total Activity) | -4.8 score on a scale | Standard Deviation 4.08 |
| Phase 1b: Placebo | Phase 2: Mean Change From Baseline in CLASI at Day 210 | CLASI-B (Total Damage) | -0.6 score on a scale | Standard Deviation 2.61 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Mean Change From Baseline in CLASI at Day 210 | CLASI-A (Total Activity) | -5.2 score on a scale | Standard Deviation 4.62 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Mean Change From Baseline in CLASI at Day 210 | CLASI-B (Total Damage) | -0.2 score on a scale | Standard Deviation 0.9 |
Comparison: Statistical Analysis for CLASI-A (Total Activity)p-value: 0.659690% CI: [-1.63, 0.94]ANCOVA
Comparison: Statistical Analysis for CLASI-B (Total Damage)p-value: 0.410590% CI: [-0.27, 0.81]ANCOVA
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.
Time frame: Baseline, Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Mean Change From Baseline in PGA | -29.2 score on a scale | Standard Deviation 20.69 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Mean Change From Baseline in PGA | -28.7 score on a scale | Standard Deviation 20.35 |
Comparison: Statistical Analysis for Day 210p-value: 0.854690% CI: [-6.07, 7.58]ANCOVA
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.
Time frame: Baseline, Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210 | -4.7 score on a scale | Standard Deviation 3.71 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210 | -3.9 score on a scale | Standard Deviation 3.31 |
p-value: 0.249890% CI: [-0.34, 1.93]ANCOVA
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.
Time frame: Baseline; Day 180
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index | 0 score on a scale | Standard Deviation 0 |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index | 0.1 score on a scale | Standard Deviation 0.24 |
Comparison: Statistical Analysis for Day 180p-value: 0.255890% CI: [-0.02, 0.12]ANCOVA
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.
Time frame: Baseline, Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1b: Placebo | 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 | Sum of Swelling | -6.8 Number of swollen/tender/active joints | Standard Deviation 5.17 |
| Phase 1b: Placebo | 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 | Sum of Tenderness | -8.3 Number of swollen/tender/active joints | Standard Deviation 7 |
| Phase 1b: Placebo | 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 | Sum of Active Joints | -6.5 Number of swollen/tender/active joints | Standard Deviation 5.54 |
| Phase 1b: Cohort 1: BOS161721 20 mg | 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 | Sum of Swelling | -5.9 Number of swollen/tender/active joints | Standard Deviation 5.05 |
| Phase 1b: Cohort 1: BOS161721 20 mg | 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 | Sum of Tenderness | -7.2 Number of swollen/tender/active joints | Standard Deviation 5.57 |
| Phase 1b: Cohort 1: BOS161721 20 mg | 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 | Sum of Active Joints | -5.6 Number of swollen/tender/active joints | Standard Deviation 4.65 |
Comparison: Statistical Analysis for Sum of Swelling for Day 210p-value: 0.445590% CI: [-0.63, 1.71]ANCOVA
Comparison: Statistical Analysis for Sum of Tenderness for Day 210p-value: 0.336790% CI: [-0.65, 2.47]ANCOVA
Comparison: Statistical Analysis for Sum of Active Joints for Day 210p-value: 0.25590% CI: [-0.34, 1.86]ANCOVA
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.
Time frame: Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210 | 12 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210 | 28 Participants |
p-value: 0.610790% CI: [-10.7, 20.5]Pearson's chi-square test
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.
Time frame: Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210 | 16 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210 | 44 Participants |
p-value: 0.123790% CI: [-0.9, 31.8]Pearson's chi-square test
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.
Time frame: Up to Day 270
Population: Safety Analysis Set (SS): Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least one evaluable post-baseline safety evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Related Serious TEAE | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | TEAE Leading to Discontinuation of Study Treatment | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Related TEAE | 4 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Related TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Any CTCAE Grade 2 or Higher TEAE | 16 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | TEAE of Special Interest | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Any CTCAE Grade 3 TEAE | 3 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Related TEAE of Special Interest | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Any TEAE | 23 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Any Related CTCAE Grade 3 or Higher TEAE | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Related Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Serious TEAE | 3 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | TEAE Resulting in Death | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Any CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Related TEAE Resulting in Death | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Any Related CTCAE Grade 2 or Higher TEAE | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Injection Site Reaction | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With AEs | Any Related CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Injection Site Reaction | 1 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Any Related CTCAE Grade 2 or Higher TEAE | 3 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Any TEAE | 44 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Related TEAE | 8 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Serious TEAE | 2 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Related Serious TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Any CTCAE Grade 3 TEAE | 6 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Any Related CTCAE Grade 3 or Higher TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Any CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Any Related CTCAE Grade 4 TEAE | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Related TEAE Leading to Discontinuation of Study Treatment | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | TEAE of Special Interest | 1 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Related TEAE of Special Interest | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Related Dose-Limiting Toxicity | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Related TEAE Resulting in Death | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With AEs | Any CTCAE Grade 2 or Higher TEAE | 25 Participants |
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.
Time frame: Days 30, 60, 90, 120, 150, 180, 210, 240, and 270
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, number analyzed in each row signifies only the participants with available data for each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 180 | 20 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 210 | 19 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 30 | 2 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 30 | 5 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 60 | 11 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 90 | 15 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 120 | 17 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 150 | 19 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 60 | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 90 | 3 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 120 | 8 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 150 | 15 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 180 | 14 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 210 | 17 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 30 | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 60 | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 90 | 3 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 120 | 8 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 150 | 15 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 180 | 14 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 210 | 17 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 120 | 15 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 180 | 37 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 150 | 22 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 210 | 40 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 150 | 22 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 30 | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 90 | 15 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 30 | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 180 | 29 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 60 | 15 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 210 | 29 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 90 | 24 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 210 | 29 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 120 | 29 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 120 | 14 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-4, Day 150 | 35 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 30 | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 60 | 10 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 180 | 28 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-5, Day 90 | 15 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit | SRI-6, Day 60 | 10 Participants |
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.
Time frame: Day 150 to Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, overall number of participants analyzed signifies only the number of participants taking oral corticosteroids at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Placebo | 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 | 7 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | 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 | 17 Participants |
p-value: 0.798590% CI: [-19.8, 14.5]Pearson's chi-square test
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.
Time frame: Days 30, 60, 90, 120, 150, 180, and 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, number analyzed in each row signifies the number of participants evaluable at any time (overall assessment) or at the given timepoint (by visit assessment).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With Medication Failures | Overall | 9 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With Medication Failures | Day 210 | 7 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With Medication Failures | Overall | 8 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With Medication Failures | Day 210 | 5 Participants |
Comparison: Statistical Analysis for Overallp-value: 0.058190% CI: [-26.7, -0.7]Pearson's chi-square test
Comparison: Statistical Analysis for Day 210p-value: 0.047190% CI: [-31.2, 3.2]Pearson's chi-square test
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.
Time frame: Days 30, 60, 90, 120, 150, 180, 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, number analyzed in each row signifies only the number of participants with a post-baseline BILAG assessment at any time (overall assessment) or at the given timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 120 | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Overall | 6 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 150 | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 60 | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 180 | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 30 | 1 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 210 | 0 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 90 | 2 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 210 | 1 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Overall | 7 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 30 | 2 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 60 | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 120 | 0 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 150 | 1 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 180 | 3 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 | Day 90 | 0 Participants |
Comparison: Statistical Analysis for Overallp-value: 0.349890% CI: [-22.9, 9.8]Pearson's chi-square test
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.
Time frame: Days 30, 60, 90, 120, 150, 180, and 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation. Here, number analyzed in each row signifies the number of participants with a post-baseline PGA assessment at any time (overall assessment) or at the given timepoint (by visit assessment).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Placebo | Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening | Overall | 13 Participants |
| Phase 1b: Placebo | Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening | Day 210 | 10 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening | Overall | 10 Participants |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening | Day 210 | 7 Participants |
Comparison: Statistical analysis for Overallp-value: 0.007290% CI: [-36.2, -7.4]Pearson's chi-square test
Comparison: Statistical Analysis for Day 210p-value: 0.014190% CI: [-30.9, -4.5]Pearson's chi-square test
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.
Time frame: Baseline; Day 210
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: Placebo | 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 | NA Days |
| Phase 1b: Cohort 1: BOS161721 20 mg | 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 | NA Days |
p-value: 0.008390% CI: [0.16, 0.68]Log-Rank Test (2-Sided)
Secondary
Phase 2: Time to Medication Failure
Participants who received prohibited medications or undergo unallowable corticosteroid (CS) usage were considered medication failures.
Time frame: Up to Day 270
Population: Full Analysis Set: Defined as all participants who received at least 1 dose (partial or complete) of study treatment and had at least 1 evaluable post baseline efficacy evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: Placebo | Phase 2: Time to Medication Failure | NA Days |
| Phase 1b: Cohort 1: BOS161721 20 mg | Phase 2: Time to Medication Failure | NA Days |
p-value: 0.047990% CI: [0.18, 0.88]Log Rank