Phase 2
Completed N=143
Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care
Source: ClinicalTrials.gov NCT03371251 ↗Enrolled (actual)
143
Serious AEs
5.6%
Results posted
Mar 2022
Primary outcomePrimary: Phase 1b: Number of Participants With Adverse Events (AEs) — 4; 2; 7; 8 Participants
Summary
This study will be conducted to assess the safety, tolerability, and immunogenicity of repeat doses of BOS161721 (20 milligrams [mg], 60 mg, and 120 mg) administered subcutaneously in adult participants with moderately to severely active Systemic Lupus Erythematosus (SLE) on limited background standard of care treatment, in order to estimate the optimal dose.
BOS161721 at the chosen dose will be compared to placebo for response on the SLE Responder Index 4, with sustained reduction of oral corticosteroids, in the same participant population.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b: Number of Participants With Adverse Events (AEs) |
4; 2; 7; 8; 1; 0 | — |
| PRIMARY Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210 |
19; 40; 19; 40; 27; 68 | 0.8434 |
| SECONDARY Phase 1b: Maximum Observed Concentration (Cmax) |
1160; 4610; 5500; 1240; 5670; 7580 | — |
| SECONDARY Phase 1b: First Time to Maximum Concentration (Tmax) |
7.01; 7.00; 8.04; 1.04; 1.00; 1.00 | — |
| SECONDARY Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) |
25100; 89400; 124000; 33600; 147000; 229000 | — |
| SECONDARY Phase 1b: Terminal Elimination Half-life (t1/2) |
75.2; 66.3; 64.3 | — |
| SECONDARY Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F) |
0.289; 0.311; 0.218 | — |
| SECONDARY Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F) |
31.4; 18.5; 23.0 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) |
12.72; -41.80; -31.35; -25.73; 18.45; -60.00 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Complement 3 (C3) and Complement (C4) Levels |
0.094; -0.032; 0.050; -0.078; 0.024; -0.038 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype |
-2.07; -5.34; -0.39; 0.27; -1.03; -0.22 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit |
-1.11; 0.48; 5.34; -11.51; -1.81; 0.40 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Anti-Sjögren's Syndrome A and B (SSA, SSB) |
0.04; 0.11; 1.02; 0.47; -0.04; 0.05 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Anti-Smith Antibody (Sm) |
-1.87; 0.74; -3.21; 3.61 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) Autoantibodies (Beta 2 Glycoprotein, Cardiolipin IgG) |
-0.03; 3.55; 0.07; -0.42; -0.11; -7.48 | — |
| SECONDARY Phase 1b: Mean Change From Baseline in Abrogation of IL-21 Gene Signature |
— | — |
| SECONDARY Phase 2: Number of Participants With an SRI-4, SRI-5, and SRI-6 Response at Each Visit |
5; 0; 11; 15; 15; 24 | — |
| SECONDARY Phase 2: Number of Participants With a Sustained Reduction From Baseline of Oral Corticosteroid (CS) (≤ 7.5 mg/Day and < Day 0 Dose) Between Day 150 and Day 210 |
7; 17 | 0.7985 |
| SECONDARY Phase 2: Number of Participants With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 |
6; 7; 1; 2; 0; 0 | 0.3498 |
| SECONDARY Phase 2: Number of Participants With Physician's Global Assessment (PGA) Worsening |
13; 10; 10; 7 | 0.0072 sig |
| SECONDARY Phase 2: Number of Participants With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210 |
12; 28 | 0.6107 |
| SECONDARY Phase 2: Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210 |
16; 44 | 0.1237 |
| SECONDARY Phase 2: Number of Participants With Medication Failures |
9; 8; 7; 5 | 0.0581 |
| SECONDARY Phase 2: Mean Change From Baseline in CLASI at Day 210 |
-4.8; -5.2; -0.6; -0.2 | 0.6596 |
| SECONDARY Phase 2: Mean Change From Baseline in PGA |
-29.2; -28.7 | 0.8546 |
| SECONDARY Phase 2: Mean Change From Baseline in the Total Number of Swollen Joints, Tender Joints, and Active Joints (Swelling and Tenderness in the Same Joint) in the American College of Rheumatology-28 (ACR-28) Joint Count |
-6.8; -5.9; -8.3; -7.2; -6.5; -5.6 | 0.4455 |
| SECONDARY Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210 |
-4.7; -3.9 | 0.2498 |
| SECONDARY Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index |
0; 0.1 | 0.2558 |
| SECONDARY Phase 2: Time to Medication Failure |
NA; NA | 0.0479 sig |
| SECONDARY Mean Percent Change in CS Administration From the Baseline Day 0 Dose Through Day 210 in Participants Receiving ≥ 7.5 mg/Day Prednisone Equivalent at Day 0 |
-36.61; -21.49 | — |
| SECONDARY Phase 2: Duration of Longest SRI-4 Response |
119.8; 124.2 | 0.7898 |
| SECONDARY Phase 2: Time to First BILAG Flare (≥ 1 New or Recurrent BILAG A or > 1 New or Recurrent BILAG B) Relative to Baseline Through Day 210 |
NA; NA | 0.0083 sig |
| SECONDARY Phase 2: Number of Participants With AEs |
23; 44; 4; 8; 3; 2 | — |
Eligibility Criteria
Inclusion Criteria
- Men and women, ages 18 to 70 years, inclusive
- Participants must be mentally capable of giving consent and there must be evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study
- Participants must have Systemic Lupus Erythematosus (SLE) as defined by meeting 4 of the Systemic Lupus International Collaborating Clinics classification criteria for SLE (with at least 1 clinical and 1 immunologic criterion OR Lupus nephritis as the sole clinical criterion in the presence of anti-nuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) antibodies), either sequentially or simultaneously
- At screening, participants must have at least 1 of the following:
- Elevated ANA ≥ 1: 80 via immunofluorescent assay at the central laboratory
- Positive anti-dsDNA or anti-Smith (anti-Sm) above the normal level as determined by the central laboratory
- At screening, the total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score must be ≥ 8, including points from at least 1 of the following clinical components:
a. Arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, and vasculitis Note: Points from lupus headache and organic brain syndrome will also be excluded from qualifying total and clinical SLEDAI-2K scores at screening and Day 0.
- A clinical SLEDAI-2K score of ≥ 6 at screening at Day 0. Clinical SLEDAI-2K score is defined as follows:
- Contains points from arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, or vasculitis
- Excludes parameters which require central laboratory results: hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA, decreased complement, thrombocytopenia, and leukopenia Note: Points from lupus headache and organic brain syndrome will also be excluded from qualifying total and clinical SLEDAI-2K scores at screening and Day 0.
- Participants must have at least 1 qualifying A or 2Bs from the following manifestations of SLE, as defined by the British Isles Lupus Assessment Group (BILAG) criteria as modified for use in this study, which must be confirmed by the central data reviewer:
- BILAG A or B score in the mucocutaneous body system. If a BILAG B score is due to BILAG number 6, mild skin eruption, the CLASI activity score including erythema and scale/hypertrophy must be ≥ 3 excluding points from mucosal ulcers and alopecia.
- BILAG A or B score in the musculoskeletal body system due to active polyarthritis Note: Hips, shoulders, back, neck, and temporomandibular joints do not count towards the total number of joints with active synovitis.
If only one "B" and no "A" score is present in the mucocutaneous body system or in the musculoskeletal body system due to arthritis, then at least 1 "B" must be present in at least 1 other body system for a total of 2 "B" BILAG body system scores.
- Participants must be currently receiving at least 1 of the following:
- Administration for a minimum of 12 weeks, and a stable dose for at least 56 days (8 weeks prior to Day 0) of the following permitted steroid sparing agents: azathioprine (AZA), mycophenolate mofetil or mycophenolic acid, chloroquine, hydroxychloroquine, or methotrexate
- If AZA, myocophenolate mofetil, mycophenolic acid, hydroxychloroquine, or MTX were discontinued prior to screening, the washout period must be ≥ 12 weeks.
- Corticosteroids (CSs) (prednisone or prednisone-equivalent) at a stable dose of up to 30 mg/day for at least 6 weeks prior to Day 0
i. For participants whose only SLE treatment is CSs, the stable CS dose must be ≥ 10 mg/day for at least 6 weeks prior to Day 0 and no more than 30 mg/day at the time of randomization.
ii. Topical steroids may be used, but the dose must be stable for at least 6 weeks prior to Day 0. PRN topical steroids are not permitted.
- Women of childbearing potential (WOCBP):
- Must have a negative serum pre
Data sourced from ClinicalTrials.gov (NCT03371251). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.