Clinical trial NCT02847598: Study to Evaluate BIIB059 (Litifilimab) in Cutaneous Lupus Erythematosus (CLE) With or Without Systemic Lupus Erythematosus (SLE)
Official title: A 2-Part Phase 2 Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of BIIB059 in Subjects With Systemic Lupus Erythematosus and Active Skin Manifestations and in Subjects With Active Cutaneous Lupus Erythematosus With or Without Systemic Manifestations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Active Cutaneous Lupus Erythematosus
Keywords: CLE, SLE, Cutaneous Lupus Erythematosus, Systemic Lupus Erythematosus
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2016-07-28
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to evaluate the efficacy of BIIB059 (litifilimab) in reducing disease activity in participants with systemic lupus erythematosus (SLE) with active cutaneous manifestations and joint involvement (Part A), and in participants with active cutaneous lupus erythematosus (CLE) (Subacute cutaneous lupus erythematosus (SCLE) or chronic CLE, including discoid lupus erythematosus (DLE)) with or without systemic manifestations (Part B). The secondary objective is to evaluate additional efficacy parameters of BIIB059 in reducing SLE/CLE disease activity, pharmacokinetic parameters, safety and tolerability of BIIB059 (Parts A and B).


Eligibility criteria: Key Inclusion Criteria:

Part A:

1. Diagnosis of systemic lupus erythematosus (SLE) fulfilling at least 4 out of 11 of the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE along with active skin manifestations and joint involvement.
2. At least 4 tender joints and at least 4 swollen joints with at least 4 of the swollen joints in the proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints and/or wrist.
3. Demonstrate at least one sign of active lupus skin disease, including acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and/or chronic cutaneous lupus erythematosus (CCLE) (e.g., discoid lupus erythematosus (DLE)), with skin activity defined by SLE Disease Activity Index 2000 (SLEDAI-2K) at the time of Screening and randomization.

Part B:

1. Active skin manifestations Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) ≥8)) and a diagnosis of cutaneous lupus erythematosus (CLE) that has been histologically confirmed (in the past or at Screening), with or without SLE manifestations.

Key Exclusion Criteria:

1. Active lupus nephritis or moderate-to-severe or chronic kidney disease.
2. Any active skin conditions other than CLE that may interfere with the study (e.g., psoriasis, non-LE skin lupus, drug-induced lupus).
3. History of chronic, recurrent (3 or more of the same type of infection in a 12-month period), or recent serious infection (e.g., pneumonia, septicemia, herpes zoster) as determined by the Investigator and requiring anti-infective treatment within 12 weeks prior to Screening.
4. Use of immunosuppressive or disease-modifying treatments for SLE or CLE that were initiated less than 12 weeks prior to Randomization.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Part A: Change From Baseline in Active Joint Count (28-joint Assessment) to Week 24
timeFrame: Baseline to Week 24
measure: Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score to Week 16
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Part A : Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at Week 24
timeFrame: Week 24
measure: Part B: Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at Week 12 and 16
timeFrame: Week 12, Week 16
measure: Part A: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12, 16 and 24
timeFrame: Baseline, Week 12, 16 and 24
measure: Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12
timeFrame: Baseline, Week 12
measure: Part A: Percentage of Participants With a >=4-point Reduction From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 24
timeFrame: Week 24
measure: Part B: Percentage of Participants With a >=4-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12 and 16
timeFrame: Week 12, Week 16
measure: Part A: Percentage of Participants With a >=7-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 24
timeFrame: Week 24
measure: Part B: Percentage of Participants With a >=7-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12 and 16
timeFrame: Week 12, Week 16
measure: Part A: Percentage of Participants Achieving a Systemic Lupus Erythematosus (SLE) Responder Index >=4 (SRI-4) at Week 24
timeFrame: Week 24
measure: Part A: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score at Week 24
timeFrame: Baseline to Week 24
measure: Part A: Percentage of Participants With no New Organ System Affected at Week 24
timeFrame: Week 24
measure: Part A: Change From Baseline in Physician's Global Assessment (PGA) of SLE Visual Analog Scale (VAS) Score at Week 24
timeFrame: Baseline to Week 24
measure: Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 36
measure: Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 28
measure: Part A: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities
timeFrame: Baseline up to Week 36
measure: Part B: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities
timeFrame: Baseline up to Week 28
measure: Part A: Number of Participants With Clinically Significant Vital Sign Abnormalities
timeFrame: Baseline up to Week 36
measure: Part B: Number of Participants With Clinically Significant Vital Sign Abnormalities
timeFrame: Baseline up to Week 28
measure: Part A: Number of Participants With Clinically Significant 12-Lead Electrocardiograms (ECGs) Abnormalities
timeFrame: Baseline up to Week 36
measure: Part B: Number of Participants With Clinically Significant 12-Lead Electrocardiograms (ECGs) Abnormalities
timeFrame: Baseline up to Week 28
measure: Part A: Number of Participants With Positive BIIB059 Antibodies
timeFrame: Baseline up to Week 24
measure: Part B: Number of Participants With Positive BIIB059 Antibodies
timeFrame: Baseline up to Week 16
measure: Part A: Absolute Change From Baseline Over Time in Immunoglobulin Levels
timeFrame: Baseline up to Week 24
measure: Part B: Absolute Change From Baseline Over Time in Immunoglobulin Levels
timeFrame: Baseline up to Week 16
measure: Part A: Absolute Change From Baseline in Vaccine Titers - Streptococcus Pneumoniae (S. Pneumoniae) at Week 24
timeFrame: Baseline to Week 24
measure: Part B: Absolute Change From Baseline in Vaccine Titers - Streptococcus Pneumoniae (S. Pneumoniae) at Week 12
timeFrame: Baseline to Week 12
measure: Part A: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 24
timeFrame: Baseline to Week 24
measure: Part B: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 12
timeFrame: Baseline to Week 12
measure: Part A: Percent Change From Baseline Over Time in Immunoglobulin Levels
timeFrame: Baseline up to Week 24
measure: Part B: Percent Change From Baseline Over Time in Immunoglobulin Levels
timeFrame: Baseline up to Week 16
measure: Part A: Percent Change From Baseline in Vaccine Titers at Week 24
timeFrame: Baseline to Week 24
measure: Part B: Percent Change From Baseline in Vaccine Titers at Week 12
timeFrame: Baseline to Week 12
measure: Part A: Serum Concentration of BIIB059
timeFrame: Part A: pre-dose on Days 1, 29, 85 and 113 and post-dose on Days 1, 8, 29, 85, 169, 197 and 253
measure: Part B: Serum Concentration of BIIB059
timeFrame: Part B: pre-dose on Days 1, 29, 85 and post-dose on Days 1, 29, 85, 113, 141, 169 and 197
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group LLC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: El Cajon
country: United States
facility: TriWest Research Associates, LLC
state: California
city: Fountain Valley
country: United States
facility: Tien Q Nguyen MD Inc
state: California
city: Hemet
country: United States
facility: MD Med Corp
state: California
city: Irvine
country: United States
facility: Universtiy of California, Irvine
state: California
city: La Jolla
country: United States
facility: The Regents of the University of California
state: California
city: La Mesa
country: United States
facility: Purushotham Akther & Rosan Kotha, MD Inc.
state: California
city: Los Angeles
country: United States
facility: Dermatology Reserach Associates
state: California
city: San Diego
country: United States
facility: University Clinical Trials
state: California
city: Santa Barbara
country: United States
facility: Richard Barthel, MD
state: California
city: Tustin
country: United States
facility: Robin K. Dore, MD, Inc.
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials Inc.
state: California
city: West Hills
country: United States
facility: Nazanin Firooz, MD Inc.
state: California
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Washington
country: United States
facility: Medical Faculty Associates, Inc.
state: District of Columbia
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Washington DC VA Medical Center
state: District of Columbia
city: Clearwater
country: United States
facility: Clinical Research of West Florida- Corporate
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research, LLC
state: Florida
city: Miami
country: United States
facility: Medical Research Center Of Miami
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Pinellas Park
country: United States
facility: DMI Research, Inc.
state: Florida
city: Sandy Springs
country: United States
facility: Advanced Medical Reserarch, PC
state: Georgia
city: Boise
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Davis Group, LTD
state: Nevada
city: Ridgewood
country: United States
facility: Valley Hospital
state: New Jersey
city: Summit
country: United States
facility: Institute for Rheumatic & Autoimmune diseases, Overlook Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Center For Rheumatology
state: New Mexico
city: Great Neck
country: United States
facility: North Shore/Long Island Jewish PRIME
state: New York
city: Chapel Hill
country: United States
facility: Univeristy of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Joint and Muscle Research Institute
state: North Carolina
city: Charlotte
country: United States
facility: American Health Research, Inc.
state: North Carolina
city: Greensboro
country: United States
facility: Medication Management, LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Clinical Trials
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Arthritis Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: North Charleston
country: United States
facility: Low Country Rheumatology, PA
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee Health Sciences Center
state: Tennessee
city: Austin
country: United States
facility: Austin Regional Clinic, P.A.
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Norfolk
country: United States
facility: Virginia Clinical Research
state: Virginia
city: Quilmes
country: Argentina
facility: Research Site
state: Buenos Aires
city: Bueno Aires
country: Argentina
facility: Research Site
state: Ciudad Autonoma Bueno Aires
city: Bueno Aires
country: Argentina
facility: Research Site
state: Ciudad Autonoma Bueno Aires
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
state: Tucuman
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: San Juan
country: Argentina
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Shumen
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Bucaramanga
country: Colombia
facility: Research Site
city: Medellín
country: Colombia
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Suwon-Si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Daejeon
country: Korea, Republic of
facility: Research Site
city: Saltillo
country: Mexico
facility: Research Site
state: Coahuila
city: Mexico
country: Mexico
facility: Research Site
state: Distrito Federal
city: Mexico
country: Mexico
facility: Research Site
state: Distrito Federal
city: Mexico
country: Mexico
facility: Research Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Research Site
state: Jalisco
city: Guadalajara
country: Mexico
facility: Research Site
state: Jalisco
city: Morelia
country: Mexico
facility: Research Site
state: Michoacán
city: Cuernavaca
country: Mexico
facility: Research Site
state: Morelos
city: Monterrey
country: Mexico
facility: Research Site
state: Neuvo Leon
city: San Luis Potosi
country: Mexico
facility: Research Site
state: San Luis Potos
city: San Luis Potosi
country: Mexico
facility: Research Site
state: San Luis Potos
city: Merida
country: Mexico
facility: Research Site
state: Yucatan
city: Durango
country: Mexico
facility: Research Site
city: Angeles City
country: Philippines
facility: Research Site
state: Pampanga
city: Batangas
country: Philippines
facility: Research Site
city: Cebu City
country: Philippines
facility: Research Site
city: Dasmarinas
country: Philippines
facility: Research Site
city: Davao City
country: Philippines
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Iloilo
country: Philippines
facility: Research Site
city: Makati City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Niska Banja
country: Serbia
facility: Research Site
city: Sabac
country: Serbia
facility: Research Site
city: Changhua
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Pathum Thani
country: Thailand
facility: Research Site
state: Klongluang
city: Chiang Mai
country: Thailand
facility: Research Site
state: Muang
city: Khon Kaen
country: Thailand
facility: Research Site
state: Muang
city: Bangkok
country: Thailand
facility: Research Site
state: Pathumwan
city: Hat Yai
country: Thailand
facility: Research Site
state: Songkhla
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Furie RA, van Vollenhoven RF, Kalunian K, Navarra S, Romero-Diaz J, Werth VP, Huang X, Clark G, Carroll H, Meyers A, Musselli C, Barbey C, Franchimont N; LILAC Trial Investigators. Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus. N Engl J Med. 2022 Sep 8;387(10):894-904. doi: 10.1056/NEJMoa2118025.
citation: Werth VP, Furie RA, Romero-Diaz J, Navarra S, Kalunian K, van Vollenhoven RF, Nyberg F, Kaffenberger BH, Sheikh SZ, Radunovic G, Huang X, Clark G, Carroll H, Naik H, Gaudreault F, Meyers A, Barbey C, Musselli C, Franchimont N; LILAC Trial Investigators. Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus. N Engl J Med. 2022 Jul 28;387(4):321-331. doi: 10.1056/NEJMoa2118024.
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
citation: Hartmann S, Biliouris K, Naik H, Rabah D, Stevenson L, Shen C, Nestorov IA, Lesko LJ, Trame MN. A clinical population pharmacokinetic/pharmacodynamic model for BIIB059, a monoclonal antibody for the treatment of systemic and cutaneous lupus erythematosus. J Pharmacokinet Pharmacodyn. 2020 Jun;47(3):255-266. doi: 10.1007/s10928-020-09688-y. Epub 2020 Apr 25.