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

NCT03371251 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BOS161721-02
• Study Type: interventional
• Target: 143
• Locations: 12 countries
• Sites: 68

Brief Summary

This study will be conducted to assess the safety, tolerability, and immunogenicity of repeat doses of BOS161721 (20 milligrams \[mg\], 60 mg, and 120 mg) administered subcutaneously in adult participants with moderately to severely active Systemic Lupus Erythematosus (SLE) on limited background standard of care treatment, in order to estimate the optimal dose. BOS161721 at the chosen dose will be compared to placebo for response on the SLE Responder Index 4, with sustained reduction of oral corticosteroids, in the same participant population.

Conditions

Systemic Lupus Erythematosus

Keywords

Adults; BOS161721; standard of care; moderately to severely active Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Participants With Adverse Events (AEs)

  The safety, tolerability, and immunogenicity of repeat doses of BOS161721 (20, 60, and 120 mg) administered SC were assessed in adult participants with moderate to severe SLE on limited background standard of care treatment, in order to estimate the optimal dose.

  Up to Day 270

• Phase 2: Number of Participants With an SLE Responder Index 4 (SRI-4) Response at Day 210

  The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group (BILAG) 2004 Index and the Physician's Global Assessment (PGA). Response based on the SRI-4 is defined by: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B) compared with baseline; and 3) no deterioration from baseline in the PGA by ≥ 30 millimeters. The SLEDAI-2K total score falls between 0 and 105, with higher scores representing increased disease activity.The SRI-4 response in participants with moderate to severe SLE is associated with broad improvements in clinical and participant-reported outcomes.

  Day 210

Secondary Outcomes (31)

• Phase 1b: Maximum Observed Concentration (Cmax)

  Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180

• Phase 1b: First Time to Maximum Concentration (Tmax)

  Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180

• Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast)

  Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180

• Phase 1b: Terminal Elimination Half-life (t1/2)

  Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180

• Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F)

  Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180

Study Arms (4)

Phase 1b: BOS161721 20, 60, 120 mg

EXPERIMENTAL

Participants will be randomized to receive a 20 milligram (mg), 60 mg, or 120 mg subcutaneous (SC) dose of BOS161721. Participants may receive 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.

Drug: BOS161721

Phase 1b: Placebo 20, 60, 120 mg

PLACEBO COMPARATOR

Participants will be randomized to receive a 20 mg, 60 mg, or 120 mg SC dose of placebo. Participants may receive 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.

Drug: Placebo

Phase 2: BOS161721

EXPERIMENTAL

Participants will be randomized to receive a 120 mg SC dose of BOS161721 (as determined from Phase 1b of the study). Participants may receive 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.

Drug: BOS161721

Phase 2: Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive a 120 mg SC dose of placebo (as determined from Phase 1b of the study). Participants may receive 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.

Drug: Placebo

Interventions

BOS161721 DRUG

SC administration

Phase 1b: BOS161721 20, 60, 120 mg; Phase 2: BOS161721

Placebo DRUG

SC administration

Phase 1b: Placebo 20, 60, 120 mg; Phase 2: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Current clinical, radiographic, or laboratory evidence of active TB
• History of active TB
• 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
• Use or planned use of concomitant medication outside of standard of baseline treatment for SLE from Day -1 or for any time during the study
• Active and clinically significant infection (bacterial, fungal, viral, or other) within 60 days prior to first dose of study drug. Clinically significant is defined as requiring systemic parenteral antibiotics or hospitalization
• A history of opportunistic infection, or a history of recurrent or severe disseminated herpes zoster or disseminated herpes simplex within the last 3 years
• Chronic viral hepatitis B (HBV) and hepatitis C (HCV), unless participant received curative treatment for HCV and has a documented negative viral load, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
• Cryptosporidium in the stool sample at screening

Sponsors & Collaborators

• Boston Pharmaceuticals: lead

Study Sites (68)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

TriWest Research Associates

El Cajon, California, 92020-4124, United States

Location

Valerius Medical Group and Research Center

Los Alamitos, California, 90720-5403, United States

Location

Westlake Medical Research

Thousand Oaks, California, 91360-3994, United States

Location

Clinical Research of West Florida

Clearwater, Florida, 33765-2616, United States

Location

Omega Research Consultants

DeBary, Florida, 32713-2260, United States

Location

Centre for Rheumatology Immunology and Arthritis

Fort Lauderdale, Florida, 33309-1715, United States

Location

Millennium Research

Ormond Beach, Florida, 32174, United States

Location

The Arthritis Center

Palm Harbor, Florida, 34684, United States

Location

Clinical Research of West Florida

Tampa, Florida, 33603, United States

Location

Clinic of Robert Hozman/Clinical Investigation Specialists, Inc.

Skokie, Illinois, 60076-1238, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Aa Mrc Llc

Grand Blanc, Michigan, 48439, United States

Location

June DO PC

Lansing, Michigan, 48910-8595, United States

Location

Joint and Muscle Research Institute

Charlotte, North Carolina, 28204-3130, United States

Location

Ramesh C. Gupta M.D.

Memphis, Tennessee, 38119-5214, United States

Location

Accurate Clinical Research Inc

Houston, Texas, 77089, United States

Location

Hospital Militar Central - Servicio de Reumatología

Buenos Aires, C1426BOR, Argentina

Location

Framingham Centro Medico

La Plata, B1902COS, Argentina

Location

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, T4000AXL, Argentina

Location

Centro de Investigaciones Reumatologicas

San Miguel de Tucumán, T4000BRD, Argentina

Location

Diagnostic Consultative Center Sveti Georgi EOOD

Plovdiv, 4000, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Plovdiv

Plovdiv, 4001, Bulgaria

Location

Medical Center - 1 - Sevlievo EOOD

Sevlievo, 5400, Bulgaria

Location

Centro Integral de Reumatologia del Caribe CIRCARIBE S.A.S

Barranquilla, 080002, Colombia

Location

Preventive Care S.A.S.

Bogotá, 110311, Colombia

Location

Medicity S.A.S.

Bucaramanga, 680003, Colombia

Location

Servimed S.A.S.

Bucaramanga, 680003, Colombia

Location

Clinica de Artritis Temprana

Cali, 760043, Colombia

Location

Hospital Pablo Tobon Uribe

Medellín, 050034, Colombia

Location

V. Tsitlanadze Scientifically-Practical Rheumatology Center Ltd

Tbilisi, 0102, Georgia

Location

Research Institute of Clinical Medicine Ltd

Tbilisi, 0112, Georgia

Location

LTD New Hospitals

Tbilisi, 0114, Georgia

Location

Mtskheta Street Clinic Ltd

Tbilisi, 0179, Georgia

Location

First Medical Center

Tbilisi, 0180, Georgia

Location

Multiprofile Clinic Consilium Medulla Ltd

Tbilisi, 0186, Georgia

Location

Qualiclinic Kft.

Budapest, 1036, Hungary

Location

DE Klinikai Központ

Debrecen, 4032, Hungary

Location

Békés Megyei Központi Kórház Pándy Kálmán Tagkórház

Gyula, 5700, Hungary

Location

Centro Integral en Reumatología S.A. de C.V. (CIRSA)

Guadalajara, 44160, Mexico

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, 44280, Mexico

Location

CLIDITER S.A. de C.V. (Centro de Investigación y Tratamiento de las Enfermedades Reumaticas)

Mexico City, 06700, Mexico

Location

Hogar Clinica San Juan De Dios

Cayma, 04000, Peru

Location

Centro de Investigación Clínica Trujillo E.I.R.L.

La Libertad, 13001, Peru

Location

Hospital Nacional Cayetano Heredia

Lima, 15102, Peru

Location

Clinica San Juan Bautista

Lima, 15431, Peru

Location

Instituto de Ginecología y Reproducción

Santiago de Surco, 15023, Peru

Location

Angeles University Foundation Medical Center

Angeles City, 2009, Philippines

Location

Southern Philippines Medical Center

Davao City, 8000, Philippines

Location

Mary Mediatrix Medical Center

Lipa City, 4217, Philippines

Location

Philippine General Hospital

Manila, 1000, Philippines

Location

University of Santo Tomas Hospital

Manila, 1015, Philippines

Location

Centrum Kliniczno - Badawcze J. Brzezicki, B. Gronkiewicz Brzezicka Spółka Lekarska

Elblag, 82-300, Poland

Location

Centrum Medyczne Plejady

Krakow, 30-363, Poland

Location

Centrum Nowoczesnych Terapii Dobry Lekarz sp. z o.o

Krakow, 31-011, Poland

Location

Centrum Medyczne AMED oddział w Łodzi

Lodz, 91-363, Poland

Location

NZOZ Lecznica MAK-MED

Nadarzyn, 05-830, Poland

Location

Prywatna Praktyka Lekarska Prof. UM dr hab. med Pawel Hrycaj

Poznan, 61-397, Poland

Location

SANUS Szpital Specjalistyczny sp. z o.o

Stalowa Wola, 37-450, Poland

Location

Reumatika-Centrum Reumatologii

Warsaw, 02-691, Poland

Location

Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL

Brasov, 500283, Romania

Location

Spitalul Clinic Judetean De Urgenta Cluj Napoca

Cluj-Napoca, 400006, Romania

Location

Spitalul Clinic de Recuperare Iasi #2

Iași, 700661, Romania

Location

National Scientific Center at Institute of Cardiology named after acad. M.D. Strazhesko

Kyiv, 03680, Ukraine

Location

Kyiv Regional Clinical Hospital

Kyiv, 04107, Ukraine

Location

Odesa Regional Clinical Hospital

Odesa, 65025, Ukraine

Location

Communal Non-Profit Enterprise "Ternopil University Clinic" of Ternopil Regional Council

Ternopil, 46002, Ukraine

Location

Vinnytsia Regional Clinical Hospital

Vinnytsia, 21018, Ukraine

Location

Related Publications (1)

• Ahmad SB, Jefferson JA. Targeting B Cells and Plasma Cells in Glomerular Disease. J Am Soc Nephrol. 2025 Jun 4;36(9):1844-1857. doi: 10.1681/ASN.0000000772.

  PMID: 40465397 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Etienne Dumont, MD
• Organization: Boston Pharmaceuticals, Inc.

clinicaltrials@bostonpharmaceuticals.com

(484) 986 8699

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 13, 2017
• Study Start: January 10, 2018
• Primary Completion: November 26, 2020
• Study Completion: November 26, 2020
• Last Updated: March 14, 2022
• Results First Posted: March 14, 2022

Record last verified: 2022-02

Locations

RO (3); UA (5); CO (6); AR (4); BU (3); PH (5); PL (8); HU (3); GE (6); US (17); ME (3); PE (5)