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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03371251
• Date of registration: 08/12/2017
• Prospective Registration: Yes
• Primary sponsor: Boston Pharmaceuticals
• Public title: Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care
• Scientific title: A Randomized Double-Blind Phase 1b/2 Combined Staggered Multiple Dose Escalation Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care
• Date of first enrolment: February 7, 2018
• Target sample size: 143
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03371251
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

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

Key inclusion & exclusion 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:

1. Elevated ANA = 1:80 via immunofluorescent assay at the central laboratory

2. Positive anti-dsDNA or anti-Smith (anti-Sm) above the normal level as determined
by the central laboratory

- At screening, the total Systemic Lupus Erythematosus Disease Activity Index 2000
(SLEDAI-2K) score must be = 8, including points from at least 1 of the following
clinical components:

a. Arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, and vasculitis
Note: Points from lupus headache and organic brain syndrome will also be excluded from
qualifying total and clinical SLEDAI-2K scores at screening and Day 0.

- A clinical SLEDAI-2K score of = 6 at screening at Day 0. Clinical SLEDAI-2K score is
defined as follows:

1. Contains points from arthritis, rash, myositis, mucosal ulcers, pleurisy,
pericarditis, or vasculitis

2. Excludes parameters which require central laboratory results: hematuria, pyuria,
urinary casts, proteinuria, positive anti-dsDNA, decreased complement,
thrombocytopenia, and leukopenia Note: Points from lupus headache and organic
brain syndrome will also be excluded from qualifying total and clinical SLEDAI-2K
scores at screening and Day 0.

- Participants must have at least 1 qualifying A or 2Bs from the following
manifestations of SLE, as defined by the British Isles Lupus Assessment Group (BILAG)
criteria as modified for use in this study, which must be confirmed by the central
data reviewer:

1. BILAG A or B score in the mucocutaneous body system. If a BILAG B score is due to
BILAG number 6, mild skin eruption, the CLASI activity score including erythema
and scale/hypertrophy must be = 3 excluding points from mucosal ulcers and
alopecia.

2. BILAG A or B score in the musculoskeletal body system due to active polyarthritis
Note: Hips, shoulders, back, neck, and temporomandibular joints do not count
towards the total number of joints with active synovitis.

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

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

1. Administration for a minimum of 12 weeks, and a stable dose for at least 56 days (8
weeks prior to Day 0) of the following permitted steroid sparing agents: azathioprine
(AZA), mycophenolate mofetil or mycophenolic acid, chloroquine, hydroxychloroquine, or
methotrexate

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

3. Corticosteroids (CSs) (prednisone or prednisone-equivalent) at a stable dose of up to
30 mg/day for at least 6 weeks prior to Day 0

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

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

- Women of childbearing potential (WOCBP):

1. Must have a negative serum pregnancy test at screening. Urine pregnancy test must
be negative prior to first dose

2. Must not be breastfeeding

3. Must agree to follow instructions for method(s) of contraception for the duration
of treatment with study drug plus 52 weeks

- Men who are sexually active with WOCBP must agree to follow instructions for method(s)
of contraception for the duration of treatment with study drug plus 52 weeks

- Participants must demonstrate willingness and ability to comply with the scheduled
study visits, treatment plans, laboratory tests, and other procedures

Exclusion Criteria:

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

- Drug-induced SLE, rather than "idiopathic" SLE

- Other systemic autoimmune disease (eg, erosive arthritis, rheumatoid arthritis [RA],
multiple sclerosis [MS], systemic sclerosis, or vasculitis not related to SLE).
RA-Lupus overlap (Rupus), and secondary Sjogren syndrome are allowed.

- Any major surgery within 6 weeks of study drug administration (Day 0) or any elective
surgery planned during the course of the study

- Any history or risk for tuberculosis (TB), specifically those with:

1. Current clinical, radiographic, or laboratory evidence of active TB

2. History of active TB

3. Latent TB defined as positive QuantiFERON-TB Gold In Tube or other diagnostic
test in the absence of clinical manifestations. Latent TB is not excluded if the
participant has documented completion of adequate course of prophylactic
treatment with regimen recommended by local health authority guideline, or the
participant has started treatment with isoniazid, or other regimen recommended by
local health authority guidelines for at least 1 month before Day 0 and continues
to receive the prophylactic treatment during study until the treatment course is
completed

- Active or unstable lupus neuropsychiatric manifestations, including but not limited to
any condition defined by BILAG A criteria, with the exception of mononeuritis
multiplex and polyneuropathy, which are allowed

- Severe proliferative lupus nephritis (World Health Organization Class III, IV), which
requires or may require induction treatment with cytotoxic agents or high dose CSs

- Con


Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: Placebo

Drug: BOS161721

Primary Outcome(s)

Phase 1b: Number of participants with a dose-limiting toxicity (DLT) [Time Frame: up to Day 270]

Phase 1b: Incidence of adverse events (AEs) [Time Frame: up to Day 270]

Phase 2: Number of participants with an SLE Responder Index 4 (SRI-4) response at Day 210 [Time Frame: Day 210]

Secondary Outcome(s)

Phase 1b: Area under the concentration-time curve (AUC) [Time Frame: Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Postdose samples will be collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180.]

Phase 1b: Mean change from Baseline in anti-double-stranded DNA (dsDNA) autoantibodies at each visit [Time Frame: Baseline (Day 0); Days 30, 60, 90, 120, 150, 180, 210, 240, and 270]

Phase 1b: Mean change from Baseline in autoantibodies at each visit [Time Frame: Baseline (Day 0); Days 30, 60, 90, 120, 150, and 180]

Phase 2: Number of participants with a DLT [Time Frame: up to Day 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 [Time Frame: Baseline; Day 150 to Day 210]

Phase 1b: Mean change from Baseline in leukocyte immunophenotype [Time Frame: Baseline (Day 0); Days 15, 30, 60, 90, and 180]

Phase 1b: Systematic clearance (CL) [Time Frame: Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Postdose samples will be collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180.]

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 [Time Frame: Baseline, up to 270 days]

Phase 2: Number of participants with Physician's Global Assessment (PGA) worsening [Time Frame: Days 30, 60, 90, 120, 150, 180, 210, 240, and 270]

Phase 2: Mean change from baseline in SLEDAI-2K at Day 210 [Time Frame: Baseline, Day 210]

Phase 2: Time to first SRI-4 response [Time Frame: Up to Day 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 [Time Frame: Baseline; Day 210]

Phase 1b: Mean change from Baseline in abrogation of IL-21 gene signature [Time Frame: Baseline (Day 0); Days 15, 90, 180, and 270]

Phase 1b: Mean change from Baseline in C3 and C4 levels [Time Frame: Baseline (Day 0); Days 30, 60, 90, 120, 150, 180, 210, 240, and 270]

Phase 1b: Volume of distribution (Vd) [Time Frame: Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Postdose samples will be collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180.]

Phase 2: Mean change from Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index [Time Frame: Baseline; Day 180]

Phase 1b: Mean change from Baseline in phosphorylated signal transducer and activator of transcription 3 (pSTAT3) [Time Frame: Baseline (Day 0); Days 30, 44, 60, and 90 (pre-dose [trough] samples only)]

Phase 2: Number of participants with an SRI-4, SRI-5, and SRI-6 response at each visit [Time Frame: Days 30, 60, 90, 120, 150, 180, 210, 240, and 270]

Phase 2: Duration of longest SRI-4 response [Time Frame: Up to Day 270]

Phase 2: Incidence of AEs [Time Frame: up to Day 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 [Time Frame: Baseline; Day 210]

Phase 1b: Plasma concentration of BOS161721 [Time Frame: Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Postdose samples will be collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180.]

Phase 2: Number of participants with a BILAG-based Composite Lupus Assessment (BICLA) response at Day 210 [Time Frame: Baseline, Day 210]

Phase 2: Number of participants with a CLASI response at Day 210 [Time Frame: Baseline, Day 210]

Phase 1b: Terminal elimination half-life (t1/2) [Time Frame: Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Postdose samples will be collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180.]

Phase 2: Mean change from baseline in the Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) at Day 210 [Time Frame: Baseline, Day 210]

Phase 2: Number of participants with new or recurrent BILAG flares (= 1 qualifying BILAG A or > 1 qualifying BILAG B) through Day 210 [Time Frame: Baseline; Day 210]

Phase 2: Time to medication failure [Time Frame: Up to Day 270]

Phase 1b: First time to maximum concentration (Tmax) [Time Frame: Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Postdose samples will be collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180.]

Phase 1b: Maximum observed concentration (Cmax) [Time Frame: Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Postdose samples will be collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180.]

Phase 2: Number of participants with medication failures [Time Frame: Up to Day 270]

Secondary ID(s)

BOS161721-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors