Trial Outcomes & Findings for Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care (NCT NCT03371251)

Last Updated: 2022-03-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

143 participants

Primary outcome timeframe

Up to Day 270

Results posted on

2022-03-14

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Phase 1b: Placebo Participants were randomized to receive 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.	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.	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	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	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.	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.
Overall Study STARTED	7	5	9	9	37	76
Overall Study COMPLETED	5	5	8	9	30	71
Overall Study NOT COMPLETED	2	0	1	0	7	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b: Placebo Participants were randomized to receive 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.	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	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.	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.
Overall Study Withdrawal by Subject	1	1	2	2
Overall Study Phase 1b: Pregnancy, Phase 2: fear of COVID-19 or local restrictions	1	0	2	3
Overall Study Adverse Event	0	0	1	0
Overall Study Decision by Sponsor	0	0	2	0

Baseline Characteristics

In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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	Phase 2: Placebo n=37 Participants 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.	Phase 2: BOS161721 120 mg n=76 Participants 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.	Total n=143 Participants Total of all reporting groups
Age, Continuous Placebo	48.1 years STANDARD_DEVIATION 17.67 • n=7 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.	—	—	—	45.7 years STANDARD_DEVIATION 12.52 • n=37 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.	—	46.1 years STANDARD_DEVIATION 13.25 • n=44 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.
Age, Continuous BOS161721	—	50.0 years STANDARD_DEVIATION 8.51 • n=5 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.	49.3 years STANDARD_DEVIATION 11.31 • n=9 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.	47.3 years STANDARD_DEVIATION 10.43 • n=9 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.	—	44.5 years STANDARD_DEVIATION 12.52 • n=76 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.	45.5 years STANDARD_DEVIATION 12.07 • n=99 Participants • In order to present the total data, the data for placebo (44 participants) and the data for BOS161721 (99 participants) have been presented in separate rows.
Sex: Female, Male Female	7 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=9 Participants	8 Participants n=9 Participants	36 Participants n=37 Participants	69 Participants n=76 Participants	133 Participants n=143 Participants
Sex: Female, Male Male	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=9 Participants	1 Participants n=9 Participants	1 Participants n=37 Participants	7 Participants n=76 Participants	10 Participants n=143 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=9 Participants	0 Participants n=9 Participants	17 Participants n=37 Participants	32 Participants n=76 Participants	53 Participants n=143 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=9 Participants	9 Participants n=9 Participants	20 Participants n=37 Participants	44 Participants n=76 Participants	90 Participants n=143 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=37 Participants	0 Participants n=76 Participants	0 Participants n=143 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=37 Participants	0 Participants n=76 Participants	0 Participants n=143 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=37 Participants	0 Participants n=76 Participants	0 Participants n=143 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=37 Participants	0 Participants n=76 Participants	0 Participants n=143 Participants
Race (NIH/OMB) Black or African American	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants	3 Participants n=9 Participants	6 Participants n=37 Participants	7 Participants n=76 Participants	18 Participants n=143 Participants
Race (NIH/OMB) White	5 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=9 Participants	6 Participants n=9 Participants	20 Participants n=37 Participants	45 Participants n=76 Participants	90 Participants n=143 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	11 Participants n=37 Participants	24 Participants n=76 Participants	35 Participants n=143 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=37 Participants	0 Participants n=76 Participants	0 Participants n=143 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
Phase 1b: Number of Participants With Adverse Events (AEs) Injection Site Reaction	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Any Treatment-Emergent Adverse Events (TEAE)	4 Participants	2 Participants	7 Participants	8 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Related TEAE	1 Participants	0 Participants	1 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Serious TEAE	1 Participants	0 Participants	2 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Related Serious TEAE	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or Higher TEAE	4 Participants	2 Participants	6 Participants	7 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Any Related CTCAE Grade 2 or Higher TEAE	1 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Any CTCAE Grade 3 TEAE	1 Participants	1 Participants	2 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Any Related CTCAE Grade 3 or Higher TEAE	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Any CTCAE Grade 4 TEAE	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) TEAE Leading to Discontinuation of Study Treatment	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Related TEAE Leading to Discontinuation of Study Treatment	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) TEAE of Special Interest	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Related TEAE of Special Interest	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Dose-Limiting Toxicity	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Related Dose-Limiting Toxicity	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) TEAE Resulting in Death	0 Participants	0 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Adverse Events (AEs) Related TEAE Resulting in Death	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 SRI-4 Response	19 Participants	40 Participants	—	—
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	40 Participants	—	—
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	68 Participants	—	—
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	68 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=5 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=9 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	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
Phase 1b: Maximum Observed Concentration (Cmax) Dose 1	1160 ng/mL Geometric Coefficient of Variation 42.0	4610 ng/mL Geometric Coefficient of Variation 54.8	5500 ng/mL Geometric Coefficient of Variation 52.3	—
Phase 1b: Maximum Observed Concentration (Cmax) Dose 2	1240 ng/mL Geometric Coefficient of Variation 23.9	5670 ng/mL Geometric Coefficient of Variation 35.7	7580 ng/mL Geometric Coefficient of Variation 45.1	—
Phase 1b: Maximum Observed Concentration (Cmax) Dose 7	2580 ng/mL Geometric Coefficient of Variation 19.1	7820 ng/mL Geometric Coefficient of Variation 144	20300 ng/mL Geometric Coefficient of Variation 37.1	—

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=5 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=9 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	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
Phase 1b: First Time to Maximum Concentration (Tmax) Dose 1	7.01 Day Interval 6.99 to 12.0	7.00 Day Interval 5.93 to 15.0	8.04 Day Interval 6.95 to 17.04	—
Phase 1b: First Time to Maximum Concentration (Tmax) Dose 2	1.04 Day Interval 1.0 to 29.02	1.00 Day Interval 0.99 to 34.97	1.00 Day Interval 1.0 to 33.03	—
Phase 1b: First Time to Maximum Concentration (Tmax) Dose 7	6.18 Day Interval 5.03 to 20.04	3.55 Day Interval 0.91 to 12.0	8.96 Day Interval 1.0 to 28.06	—

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=5 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=9 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	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
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	89400 day*ng/mL Geometric Coefficient of Variation 51.7	124000 day*ng/mL Geometric Coefficient of Variation 40.5	—
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	147000 day*ng/mL Geometric Coefficient of Variation 29.7	229000 day*ng/mL Geometric Coefficient of Variation 47.9	—
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	460000 day*ng/mL Geometric Coefficient of Variation 173	1400000 day*ng/mL Geometric Coefficient of Variation 38.7	—

SECONDARY outcome

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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=5 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=1 Participants 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	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
Phase 1b: Terminal Elimination Half-life (t1/2)	75.2 Day Geometric Coefficient of Variation 19.9	66.3 Day Geometric Coefficient of Variation 35.4	64.3 Day Geometric Coefficient of Variation NA Not calculated for 1 participant	—

SECONDARY outcome

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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=5 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=8 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	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
Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F)	0.289 Liter/day Geometric Coefficient of Variation 18.3	0.311 Liter/day Geometric Coefficient of Variation 179	0.218 Liter/day Geometric Coefficient of Variation 38.8	—

SECONDARY outcome

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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=5 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=1 Participants 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	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
Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F)	31.4 Liter Geometric Coefficient of Variation 33.2	18.5 Liter Geometric Coefficient of Variation 39.6	23.0 Liter Geometric Coefficient of Variation NA Not calculated for 1 participant	—

SECONDARY outcome

Timeframe: 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.

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and pharmacodynamic (PD) data in participants with moderate to severe SLE.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
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	-41.80 Percentage Standard Deviation 24.631	-31.35 Percentage Standard Deviation 20.281	-25.73 Percentage Standard Deviation 20.895
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	-60.00 Percentage Standard Deviation 19.672	-32.99 Percentage Standard Deviation 19.899	-26.57 Percentage Standard Deviation 20.856
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	-59.46 Percentage Standard Deviation 20.310	-32.68 Percentage Standard Deviation 19.214	-25.91 Percentage Standard Deviation 20.850
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	-67.48 Percentage Standard Deviation 15.630	-33.03 Percentage Standard Deviation 19.637	-26.74 Percentage Standard Deviation 20.962

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
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	-0.032 gram/Litre Standard Deviation 0.0876	0.050 gram/Litre Standard Deviation 0.3424	-0.078 gram/Litre Standard Deviation 0.2879
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	-0.038 gram/Litre Standard Deviation 0.0370	-0.007 gram/Litre Standard Deviation 0.0783	-0.024 gram/Litre Standard Deviation 0.0410

SECONDARY outcome

Timeframe: 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.

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.

Outcome measures

SECONDARY outcome

Timeframe: 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..

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
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	0.48 International units per millilitre Standard Deviation 0.410	5.34 International units per millilitre Standard Deviation 9.053	-11.51 International units per millilitre Standard Deviation 32.444
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	0.40 International units per millilitre Standard Deviation 0.376	8.06 International units per millilitre Standard Deviation 18.430	-6.11 International units per millilitre Standard Deviation 15.612
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	0.00 International units per millilitre Standard Deviation 0.187	19.31 International units per millilitre Standard Deviation 48.594	-13.44 International units per millilitre Standard Deviation 35.152
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 0.270	0.41 International units per millilitre Standard Deviation 0.598	12.30 International units per millilitre Standard Deviation 35.583	-15.58 International units per millilitre Standard Deviation 47.248
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	0.62 International units per millilitre Standard Deviation 0.709	17.39 International units per millilitre Standard Deviation 50.086	-11.18 International units per millilitre Standard Deviation 38.152
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	0.52 International units per millilitre Standard Deviation 0.584	8.00 International units per millilitre Standard Deviation 21.169	-17.13 International units per millilitre Standard Deviation 49.897
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	0.07 International units per millilitre Standard Deviation 0.540	6.76 International units per millilitre Standard Deviation 20.173	-17.96 International units per millilitre Standard Deviation 50.274
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	0.34 International units per millilitre Standard Deviation 1.117	6.81 International units per millilitre Standard Deviation 21.903	-18.35 International units per millilitre Standard Deviation 47.898
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	0.37 International units per millilitre Standard Deviation 0.700	7.99 International units per millilitre Standard Deviation 24.116	-9.71 International units per millilitre Standard Deviation 27.833

SECONDARY outcome

Timeframe: 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.

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
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	0.11 U/mL Standard Deviation 0.108	1.02 U/mL Standard Deviation 2.639	0.47 U/mL Standard Deviation 1.668
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	0.05 U/mL Standard Deviation 0.112	0.19 U/mL Standard Deviation 0.567	-2.25 U/mL Standard Deviation 4.861
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 0.000	0.00 U/mL Standard Deviation 0.000	-2.62 U/mL Standard Deviation 7.867	-4.36 U/mL Standard Deviation 8.684

SECONDARY outcome

Timeframe: 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.

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm)	-1.87 U/mL Standard Deviation 4.827	0.74 U/mL Standard Deviation 0.391	-3.21 U/mL Standard Deviation 9.419	3.61 U/mL Standard Deviation 19.504

SECONDARY outcome

Timeframe: 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.

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
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	3.55 U/mL Standard Deviation 5.559	0.07 U/mL Standard Deviation 0.585	-0.42 U/mL Standard Deviation 0.180
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	-7.48 U/mL Standard Deviation 23.684	-0.14 U/mL Standard Deviation 0.882	0.02 U/mL Standard Deviation 0.787

SECONDARY outcome

Timeframe: 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.

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in participants with moderate to severe SLE.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-4, Day 30	5 Participants	0 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-4, Day 60	11 Participants	15 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-4, Day 90	15 Participants	24 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-4, Day 120	17 Participants	29 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-4, Day 150	19 Participants	35 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-4, Day 180	20 Participants	37 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-4, Day 210	19 Participants	40 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-5, Day 30	2 Participants	0 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-5, Day 60	1 Participants	10 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-5, Day 90	3 Participants	15 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-5, Day 120	8 Participants	15 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-5, Day 150	15 Participants	22 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-5, Day 180	14 Participants	29 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-5, Day 210	17 Participants	29 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-6, Day 30	1 Participants	0 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-6, Day 60	1 Participants	10 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-6, Day 90	3 Participants	15 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-6, Day 120	8 Participants	14 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-6, Day 150	15 Participants	22 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-6, Day 180	14 Participants	28 Participants	—	—
Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit SRI-6, Day 210	17 Participants	29 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=25 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=67 Participants 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.	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	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
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	17 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
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	0 Participants	—	—
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	0 Participants	—	—
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	1 Participants	—	—
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	3 Participants	—	—
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	1 Participants	—	—
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	7 Participants	—	—
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	2 Participants	—	—
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	0 Participants	—	—

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening Overall	13 Participants	10 Participants	—	—
Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening Day 210	10 Participants	7 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Number of Participants With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210	12 Participants	28 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210	16 Participants	44 Participants	—	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Number of Participants With Medication Failures Overall	9 Participants	8 Participants	—	—
Phase 2: Number of Participants With Medication Failures Day 210	7 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
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	-5.2 score on a scale Standard Deviation 4.62	—	—
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	-0.2 score on a scale Standard Deviation 0.90	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Mean Change From Baseline in PGA	-29.2 score on a scale Standard Deviation 20.69	-28.7 score on a scale Standard Deviation 20.35	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
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	-5.9 Number of swollen/tender/active joints Standard Deviation 5.05	—	—
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 7.00	-7.2 Number of swollen/tender/active joints Standard Deviation 5.57	—	—
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	-5.6 Number of swollen/tender/active joints Standard Deviation 4.65	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210	-4.7 score on a scale Standard Deviation 3.71	-3.9 score on a scale Standard Deviation 3.31	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=30 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=67 Participants 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.	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	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
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	0.1 score on a scale Standard Deviation 0.24	—	—

SECONDARY outcome

Timeframe: 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.

Participants who received prohibited medications or undergo unallowable corticosteroid (CS) usage were considered "medication failures".

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Time to Medication Failure	NA Days Median was not established based on the number of medication failures observed.	NA Days Median was not established based on the number of medication failures observed.	—	—

SECONDARY outcome

Timeframe: 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.

The percent reduction in CS administration from Day 0 through Day 210 was determined based on the average daily CS usage.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=13 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=45 Participants 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.	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	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
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	-21.49 Percent Reduction in Dose (mg/day) Standard Deviation 26.950	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
Phase 2: Duration of Longest SRI-4 Response	119.8 Days Standard Deviation 68.26	124.2 Days Standard Deviation 68.48	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=75 Participants 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.	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	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
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 Median was not established based on the number of BILAG flares observed.	NA Days Median was not established based on the number of BILAG flares observed.	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1b: Placebo n=37 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=76 Participants 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.	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	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
Phase 2: Number of Participants With AEs Any TEAE	23 Participants	44 Participants	—	—
Phase 2: Number of Participants With AEs Related TEAE	4 Participants	8 Participants	—	—
Phase 2: Number of Participants With AEs Serious TEAE	3 Participants	2 Participants	—	—
Phase 2: Number of Participants With AEs Related Serious TEAE	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Any CTCAE Grade 2 or Higher TEAE	16 Participants	25 Participants	—	—
Phase 2: Number of Participants With AEs Any Related CTCAE Grade 2 or Higher TEAE	0 Participants	3 Participants	—	—
Phase 2: Number of Participants With AEs Any CTCAE Grade 3 TEAE	3 Participants	6 Participants	—	—
Phase 2: Number of Participants With AEs Any Related CTCAE Grade 3 or Higher TEAE	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Any CTCAE Grade 4 TEAE	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Any Related CTCAE Grade 4 TEAE	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs TEAE Leading to Discontinuation of Study Treatment	1 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Related TEAE Leading to Discontinuation of Study Treatment	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs TEAE of Special Interest	0 Participants	1 Participants	—	—
Phase 2: Number of Participants With AEs Related TEAE of Special Interest	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Dose-Limiting Toxicity	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Related Dose-Limiting Toxicity	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs TEAE Resulting in Death	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Related TEAE Resulting in Death	0 Participants	0 Participants	—	—
Phase 2: Number of Participants With AEs Injection Site Reaction	1 Participants	1 Participants	—	—

Adverse Events

Phase 1b: Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Phase 1b: Cohort 1: BOS161721 20 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Phase 1b: Cohort 2: BOS161721 60 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Phase 1b: Cohort 3: BOS161721 120 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Phase 2: Placebo

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Phase 2: BOS161721 120 mg

Serious events: 2 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1b: Placebo n=7 participants at risk 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 participants at risk 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 participants at risk 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 participants at risk 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	Phase 2: Placebo n=37 participants at risk 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.	Phase 2: BOS161721 120 mg n=76 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Respiratory, thoracic and mediastinal disorders Lupus Pneumonitis	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal Proliferative Breast Lesion	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of Skin	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Blood and lymphatic system disorders Anaemia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Congenital, familial and genetic disorders Exomphalos	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Hepatobiliary disorders Biliary Colic	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Pyelonephritis Acute	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270

Other adverse events

Other adverse events
Measure	Phase 1b: Placebo n=7 participants at risk 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 participants at risk 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 participants at risk 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 participants at risk 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	Phase 2: Placebo n=37 participants at risk 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.	Phase 2: BOS161721 120 mg n=76 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	5.4% 2/37 • Number of events 2 • Up to Day 270	0.00% 0/76 • Up to Day 270
Blood and lymphatic system disorders Iron Deficiency Anaemia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Cardiac disorders Bundle Branch Block Right	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Eye disorders Cataract	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Eye disorders Diplopia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Gastrointestinal disorders Nausea	14.3% 1/7 • Number of events 2 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	22.2% 2/9 • Number of events 2 • Up to Day 270	2.7% 1/37 • Number of events 2 • Up to Day 270	5.3% 4/76 • Number of events 4 • Up to Day 270
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	8.1% 3/37 • Number of events 3 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Gastrointestinal disorders Constipation	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	2.6% 2/76 • Number of events 2 • Up to Day 270
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Gastrointestinal disorders Abdominal Pain	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Gastrointestinal disorders Dental Caries	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Gastrointestinal disorders Dry Mouth	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Gastrointestinal disorders Tongue Ulceration	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
General disorders Non-Cardiac Chest Pain	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	22.2% 2/9 • Number of events 2 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Nasopharyngitis	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	8.1% 3/37 • Number of events 4 • Up to Day 270	9.2% 7/76 • Number of events 9 • Up to Day 270
Infections and infestations Urinary Tract Infection	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 3 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	10.8% 4/37 • Number of events 4 • Up to Day 270	5.3% 4/76 • Number of events 6 • Up to Day 270
Infections and infestations Pharyngitis	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	5.4% 2/37 • Number of events 2 • Up to Day 270	5.3% 4/76 • Number of events 4 • Up to Day 270
Infections and infestations Upper Respiratory Tract Infection	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	22.2% 2/9 • Number of events 2 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Bronchitis	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	2.6% 2/76 • Number of events 2 • Up to Day 270
Infections and infestations Escherichia Urinary Tract Infection	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	5.4% 2/37 • Number of events 2 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Infections and infestations Cervicitis	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Pneumonia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Infections and infestations Vulvovaginal Mycotic Infection	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Infections and infestations Diverticulitis	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Gastroenteritis Viral	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Herpes Zoster	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Infected Bite	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Nasal Abscess	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Otitis Media Acute	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Sinusitis	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 3 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Injury, poisoning and procedural complications Fall	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Injury, poisoning and procedural complications Animal Bite	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Injury, poisoning and procedural complications Ankle Fracture	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Injury, poisoning and procedural complications Ligament Sprain	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Investigations White Blood Cells Urine Positive	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 2 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 2 • Up to Day 270	2.6% 2/76 • Number of events 5 • Up to Day 270
Investigations Blood Pressure Increased	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Investigations Weight Increased	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Metabolism and nutrition disorders Type 2 Diabetes Mellitus	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	8.1% 3/37 • Number of events 4 • Up to Day 270	2.6% 2/76 • Number of events 2 • Up to Day 270
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	3.9% 3/76 • Number of events 3 • Up to Day 270
Musculoskeletal and connective tissue disorders Fibromyalgia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Musculoskeletal and connective tissue disorders Muscle Spasms	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 2 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Musculoskeletal and connective tissue disorders Sjogren's Syndrome	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	0.00% 0/76 • Up to Day 270
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Nervous system disorders Headache	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	5.4% 2/37 • Number of events 2 • Up to Day 270	5.3% 4/76 • Number of events 6 • Up to Day 270
Nervous system disorders Migraine	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270
Nervous system disorders Cervical Radiculopathy	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Psychiatric disorders Confusional State	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Psychiatric disorders Depression	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Psychiatric disorders Insomnia	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Reproductive system and breast disorders Menorrhagia	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	5.4% 2/37 • Number of events 2 • Up to Day 270	0.00% 0/76 • Up to Day 270
Reproductive system and breast disorders Adnexa Uteri Pain	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	11.1% 1/9 • Number of events 2 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	14.3% 1/7 • Number of events 1 • Up to Day 270	0.00% 0/5 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	0.00% 0/76 • Up to Day 270
Vascular disorders Hypertension	0.00% 0/7 • Up to Day 270	20.0% 1/5 • Number of events 1 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	2.7% 1/37 • Number of events 1 • Up to Day 270	2.6% 2/76 • Number of events 4 • Up to Day 270
Vascular disorders Deep Vein Thrombosis	0.00% 0/7 • Up to Day 270	0.00% 0/5 • Up to Day 270	11.1% 1/9 • Number of events 1 • Up to Day 270	0.00% 0/9 • Up to Day 270	0.00% 0/37 • Up to Day 270	1.3% 1/76 • Number of events 1 • Up to Day 270

Additional Information

Etienne Dumont, MD

Boston Pharmaceuticals, Inc.

Phone: (484) 986 8699

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Phase 1b: Placebo n=7 Participants 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.	Phase 1b: Cohort 1: BOS161721 20 mg n=5 Participants 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.	Phase 1b: Cohort 2: BOS161721 60 mg n=9 Participants 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	Phase 1b: Cohort 3: BOS161721 120 mg n=9 Participants 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
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype IgD-CD27+% of CD19+	-0.21 Change in percentage of cells Standard Deviation 3.866	-0.48 Change in percentage of cells Standard Deviation 3.891	2.02 Change in percentage of cells Standard Deviation 3.751	0.70 Change in percentage of cells Standard Deviation 3.740
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype CD19+% of CD45+ Lymphocytes	-2.07 Change in percentage of cells Standard Deviation 3.201	-5.34 Change in percentage of cells Standard Deviation 4.663	-0.39 Change in percentage of cells Standard Deviation 4.201	0.27 Change in percentage of cells Standard Deviation 3.481
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	-0.22 Change in percentage of cells Standard Deviation 2.406	-0.38 Change in percentage of cells Standard Deviation 1.495	-1.08 Change in percentage of cells Standard Deviation 2.266
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype CD4+CD8-% of CD3+	-1.01 Change in percentage of cells Standard Deviation 10.866	-3.08 Change in percentage of cells Standard Deviation 5.272	0.88 Change in percentage of cells Standard Deviation 7.434	-5.04 Change in percentage of cells Standard Deviation 7.671
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype CD56+% OF CD45+ Lymphocytes	-0.56 Change in percentage of cells Standard Deviation 2.093	-5.76 Change in percentage of cells Standard Deviation 4.231	-2.38 Change in percentage of cells Standard Deviation 2.461	2.04 Change in percentage of cells Standard Deviation 7.984
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype CD8+CD4-% of CD3+	-3.00 Change in percentage of cells Standard Deviation 7.792	-1.38 Change in percentage of cells Standard Deviation 4.467	-2.92 Change in percentage of cells Standard Deviation 5.010	-0.24 Change in percentage of cells Standard Deviation 6.517
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype CXCR5+% of CD25+CD127-	0.20 Change in percentage of cells Standard Deviation 4.676	7.02 Change in percentage of cells Standard Deviation 3.371	10.62 Change in percentage of cells Standard Deviation 11.963	0.63 Change in percentage of cells Standard Deviation 5.915
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype CXCR5+% of CD4+CD8-	0.81 Change in percentage of cells Standard Deviation 12.373	15.18 Change in percentage of cells Standard Deviation 7.564	13.14 Change in percentage of cells Standard Deviation 16.091	-0.69 Change in percentage of cells Standard Deviation 7.208
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype ICOS+% of CD25+CD127-	8.59 Change in percentage of cells Standard Deviation 10.618	1.56 Change in percentage of cells Standard Deviation 3.840	12.93 Change in percentage of cells Standard Deviation 11.905	4.27 Change in percentage of cells Standard Deviation 17.059
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype ICOS+% of CD4+CD8-	3.93 Change in percentage of cells Standard Deviation 6.906	0.14 Change in percentage of cells Standard Deviation 5.227	5.01 Change in percentage of cells Standard Deviation 5.053	0.54 Change in percentage of cells Standard Deviation 15.534
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype IgD+C27-% of CD19+	0.20 Change in percentage of cells Standard Deviation 7.127	2.42 Change in percentage of cells Standard Deviation 5.882	-1.07 Change in percentage of cells Standard Deviation 4.748	-0.80 Change in percentage of cells Standard Deviation 6.031
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype IgD+CD27+% of CD19+	1.29 Change in percentage of cells Standard Deviation 1.785	-3.24 Change in percentage of cells Standard Deviation 6.080	-1.24 Change in percentage of cells Standard Deviation 2.823	1.00 Change in percentage of cells Standard Deviation 3.260
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	0.56 Change in percentage of cells Standard Deviation 1.688	-0.42 Change in percentage of cells Standard Deviation 2.351	0.16 Change in percentage of cells Standard Deviation 1.385
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	0.04 Change in percentage of cells Standard Deviation 0.089	0.08 Change in percentage of cells Standard Deviation 0.172	-0.02 Change in percentage of cells Standard Deviation 0.130
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	-0.20 Change in percentage of cells Standard Deviation 0.354	0.59 Change in percentage of cells Standard Deviation 1.437	-0.63 Change in percentage of cells Standard Deviation 1.081
Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype IgD-CD27-% of CD19+	-1.29 Change in percentage of cells Standard Deviation 2.963	1.36 Change in percentage of cells Standard Deviation 2.373	0.32 Change in percentage of cells Standard Deviation 2.059	-0.83 Change in percentage of cells Standard Deviation 1.648
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	3.30 Change in percentage of cells Standard Deviation 5.039	7.41 Change in percentage of cells Standard Deviation 6.064	-8.49 Change in percentage of cells Standard Deviation 13.258
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	4.14 Change in percentage of cells Standard Deviation 4.146	6.39 Change in percentage of cells Standard Deviation 5.882	-9.01 Change in percentage of cells Standard Deviation 13.036