Clinical trial NCT03978520: A Study to Investigate the Safety and Efficacy of Elsubrutinib and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus (SLE)
Official title: A Phase 2 Study to Investigate the Safety and Efficacy of Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599 Combination) in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: Systemic Lupus Erythematosus (SLE)
ABBV-105
Upadacitinib
ABBV-599
Elsubrutinib
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2019-06-07
Enrollment: 341
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this study was to evaluate the safety and efficacy of elsubrutinib, upadacitinib (UPA), and ABBV-599 (elsubrutinib/upadacitinib) High Dose and Low Dose combinations vs placebo for the treatment of signs and symptoms of Systemic Lupus Erythematosus (SLE) in participants with moderately to severely active SLE and to define doses for further development.


Eligibility criteria: Inclusion Criteria:

* Participant has clinical diagnosis of Systemic Lupus Erythematosus (SLE) at least 24 weeks prior to Screening, meeting at least 4 of the 11 revised Criteria for Classification of SLE according to the 1997 Update of the 1982 American College of Rheumatology (ACR) OR meeting at least 4 of the 2012 SLICC classification criteria, including at least 1 clinical criterion and 1 immunologic criterion.
* At Screening, must have at least one of the following:

  * antinuclear antibody (ANA)+ (titer ≥ 1:80)
  * anti-dsDNA+
  * anti-Smith+
* SLEDAI-2K (SLE Disease Activity Index) ≥ 6 despite background therapy as reported and independently adjudicated (clinical score ≥ 4, excluding lupus headache and/or organic brain syndrome) at Screening:

  * If 4 points of the required entry points are for arthritis, there must also be a minimum of 3 tender and 3 swollen joints.
  * If participant has rash and Principal Investigator (PI) considers it to be attributable to SLE, participant must consent to skin photograph collection for adjudication.
  * Score must be re-confirmed at the Baseline visit.
* Physician's Global Assessment (PhGA) ≥ 1 during screening period.
* Must be on background treatment, stable for 30 days prior to Baseline and throughout the study with antimalarial(s), prednisone (or prednisone equivalent) (≤ 20 mg), azathioprine (≤ 150 mg), mycophenolate (\<2 g), leflunomide (≤ 20 mg), cyclosporine, tacrolimus, and/or methotrexate (MTX) (≤ 20 mg).

  * No combinations of the above with immunomodulators other than prednisone (or equivalents) and antimalarials.

Exclusion Criteria:

- Participant using intravenous (IV) or intramuscular (IM) corticosteroids greater than or equal to a 40 mg prednisone-equivalent bolus within 30 days of planned randomization.

Primary outcomes:
measure: Percentage of Participants Achieving SLE Responder Index (SRI)-4 and Steroid Dose ≤ 10 mg Prednisone Equivalent Once a Day (QD) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Participants Achieving SLE Responder Index (SRI)-4 at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG) Based Combined Lupus Assessment (BICLA) Response at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Daily Prednisone Dose at Week 24
timeFrame: From Baseline to Week 24
measure: Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Flare Index Through Week 24
timeFrame: From Baseline to Week 24
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC /ID# 214522
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis and Rheumotology Research, PLLC /ID# 211329
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis and Rheumotology Research, PLLC /ID# 214267
state: Arizona
city: Jonesboro
country: United States
facility: Arthritis and Rheumatism Associates /ID# 211411
state: Arkansas
city: Beverly Hills
country: United States
facility: Wallace Rheumatic Studies Center, LLC /ID# 211600
state: California
city: La Palma
country: United States
facility: Arthritis & Osteo Medical Ctr /ID# 228235
state: California
city: Los Alamitos
country: United States
facility: Valerius Medical Group & Research Center /ID# 211599
state: California
city: San Leandro
country: United States
facility: East Bay Rheumatology Medical /ID# 211638
state: California
city: Torrance
country: United States
facility: The Lundquist Institute at Harbor-UCLA Medical Center /ID# 213402
state: California
city: Tujunga
country: United States
facility: Medvin Clinical Research /ID# 211996
state: California
city: Upland
country: United States
facility: Inland Rheum Clin Trials Inc. /ID# 213617
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital /ID# 211314
state: Colorado
city: New Haven
country: United States
facility: Yale University /ID# 212824
state: Connecticut
city: Washington
country: United States
facility: Medstar Health Research Institute /ID# 213335
state: District of Columbia
city: Aventura
country: United States
facility: Arthritis & Rheumatic Disease Specialties /ID# 214052
state: Florida
city: Miami
country: United States
facility: LeJenue Research Associates /ID# 212327
state: Florida
city: Miami
country: United States
facility: Ctr Arthritis & Rheumatic Dise /ID# 212326
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research /ID# 219099
state: Florida
city: Plantation
country: United States
facility: IRIS Research and Development, LLC /ID# 213053
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates /ID# 211881
state: Florida
city: Tampa
country: United States
facility: BayCare Medical Group, Inc. /ID# 218818
state: Florida
city: Oak Brook
country: United States
facility: Affinity Clinical Research /ID# 211496
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates /ID# 212251
state: Illinois
city: Evansville
country: United States
facility: Qualmedica Research, LLC /ID# 214765
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics /ID# 215246
state: Iowa
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research /ID# 211610
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 212321
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System /ID# 211676
state: Michigan
city: Lansing
country: United States
facility: June DO, PC /ID# 211674
state: Michigan
city: Saint Louis
country: United States
facility: West County Rheumatology /ID# 225051
state: Missouri
city: Brooklyn
country: United States
facility: NYU Langone Ambulatory Care Brooklyn Heights /ID# 211548
state: New York
city: New York
country: United States
facility: NYU Langone Orthopedic Center /ID# 213620
state: New York
city: Columbus
country: United States
facility: Ohio State University - Wexner Medical Center /ID# 211636
state: Ohio
city: Vandalia
country: United States
facility: STAT Research, Inc. /ID# 211404
state: Ohio
city: Tulsa
country: United States
facility: Premier Rheumatology of Oklahoma /ID# 213850
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allegheny Health Network Research Institute /ID# 211607
state: Pennsylvania
city: Memphis
country: United States
facility: Univ TN Health Sciences Ctr /ID# 212177
state: Tennessee
city: Memphis
country: United States
facility: Dr. Ramesh Gupta /ID# 213381
state: Tennessee
city: Austin
country: United States
facility: Tekton Research, Inc. /ID# 211521
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc. /ID# 214182
state: Texas
city: Carrollton
country: United States
facility: Trinity Universal Research Associates - Carrollton /ID# 211527
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Management /ID# 213571
state: Texas
city: Lubbock
country: United States
facility: West Texas Clinical Research /ID# 211529
state: Texas
city: Mesquite
country: United States
facility: SW Rheumatology Res. LLC /ID# 211520
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic /ID# 213500
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center /ID# 211457
state: Washington
city: Beckley
country: United States
facility: Rheumatology and Pulmonary Clinic /ID# 211398
state: West Virginia
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich /ID# 221685
state: Buenos Aires
city: La Plata
country: Argentina
facility: Hospital Interzonal General de Agudos General Jose de San Martin /ID# 211679
state: Buenos Aires
city: Quilmes
country: Argentina
facility: CER Instituto Medico /ID# 222757
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Aprillus Asistencia e Investigacion /ID# 211630
state: Ciuadad Autonoma De Buenos Aires
city: Rosario
country: Argentina
facility: Centro de Enfermedades del Hígado y Aparato Digestivo /ID# 211634
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto CAICI S.R.L /ID# 211633
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Medicas Tucuman /ID# 212714
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones Clinicas Tucuman /ID# 211942
state: Tucuman
city: Cordoba
country: Argentina
facility: Hospital Cordoba /ID# 212200
city: Botany
country: Australia
facility: Emeritus Research Sydney /ID# 222983
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital /ID# 222982
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital /ID# 212667
state: Queensland
city: Maroochydore
country: Australia
facility: Rheumatology Research Unit Sunshine Coast /ID# 211902
state: Queensland
city: Southport
country: Australia
facility: Griffith University /ID# 223543
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital /ID# 211901
state: South Australia
city: Camberwell
country: Australia
facility: Emeritus Research /ID# 211903
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre /ID# 212313
state: Victoria
city: Fitzroy Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne /ID# 212311
state: Victoria
city: Plovdiv
country: Bulgaria
facility: UMHAT Kaspela EOOD /ID# 223141
city: Sofia
country: Bulgaria
facility: UMHAT Sveti Ivan Rilski /ID# 223139
city: Sofia
country: Bulgaria
facility: UMHAT Sveti Ivan Rilski /ID# 223140
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - McMaster University Medical Centre /ID# 212662
state: Ontario
city: London
country: Canada
facility: St. Josephs Health Care Centre /ID# 212331
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital /ID# 213336
state: Ontario
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke Inc. /ID# 217734
state: Quebec
city: Hefei
country: China
facility: Anhui Provincial Hospital /ID# 211812
state: Anhui
city: Beijing
country: China
facility: Peking Union Medical College Hospital /ID# 211614
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital /ID# 211811
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital Central South University /ID# 212919
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital /ID# 211818
state: Jiangsu
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University /ID# 213976
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital /ID# 211819
state: Shanghai
city: Urumqi
country: China
facility: People's Hospital of Xinjiang /ID# 211821
city: Barranquilla
country: Colombia
facility: Centro Integral de Reumatologia del Caribe Circaribe SAS /ID# 211894
state: Atlantico
city: Bogota
country: Colombia
facility: Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 211895
state: Cundinamarca
city: Chia
country: Colombia
facility: Preventive Care Sas /Id# 211896
state: Cundinamarca
city: Zipaquira
country: Colombia
facility: Healthy Medical Center SAS /ID# 211899
state: Cundinamarca
city: Medellin
country: Colombia
facility: Clinica Universitaria Bolivari /ID# 211897
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 211829
state: Hauts-de-France
city: Bordeaux
country: France
facility: CHU Bordeaux - Hopital Pellegrin /ID# 211832
city: Le Kremlin Bicetre
country: France
facility: AP-HP - Hôpital Bicêtre /ID# 211968
city: Paris
country: France
facility: Hopital Pitie Salpetriere /ID# 211831
city: Strasbourg cedex
country: France
facility: CHU Strasbourg - Hopital Civil /ID# 211981
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf /ID# 212408
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 212674
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 211988
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 212770
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont /ID# 212042
state: Hajdu-Bihar
city: Veszprém
country: Hungary
facility: Vital Medical Center Orvosi es Fogaszati Kozpont /ID# 212796
state: Veszprem
city: Budapest
country: Hungary
facility: Orszagos Reumatologiai es Fizioterapias Intezet /ID# 211827
city: Gyula
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz /ID# 216971
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant Anna /ID# 211861
state: Ferrara
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 212195
state: Lazio
city: Milan
country: Italy
facility: ASST Gaetano Pini/Presidio Ospedaliero Pini /ID# 215063
city: Udine
country: Italy
facility: Azienda Ospedaliera Universitaria Friuli Centrale/Presidio Ospedaliero Universit /ID# 211858
city: Nagoya-shi
country: Japan
facility: Chukyo Hospital /ID# 222625
state: Aichi
city: Nagoya-shi
country: Japan
facility: NHO Nagoya Medical Center /ID# 213974
state: Aichi
city: Fukuoka-shi
country: Japan
facility: Hamanomachi Hospital /ID# 213696
state: Fukuoka
city: Kitakyushu-shi
country: Japan
facility: Hospital of the University of Occupational and Environmental Health, Japan /ID# 217548
state: Fukuoka
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital /ID# 213913
state: Fukushima
city: Hiroshima-shi
country: Japan
facility: Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 213694
state: Hiroshima
city: Asahikawa-shi
country: Japan
facility: National Hospital Organization Asahikawa Medical Center /ID# 213846
state: Hokkaido
city: Tomakomai-shi
country: Japan
facility: Tomakomai City Hospital /ID# 214234
state: Hokkaido
city: Ono-shi
country: Japan
facility: Kita-harima Medical Center /ID# 215474
state: Hyogo
city: Kagoshima-shi
country: Japan
facility: EIRAKU Internal Medicine Clinic /ID# 215419
state: Kagoshima
city: Yokohama-shi
country: Japan
facility: Yokohama Rosai Hospital /ID# 213690
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Kumamoto Shinto General Hospital /ID# 215347
state: Kumamoto
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 213693
state: Miyagi
city: Matsumoto-shi
country: Japan
facility: Shinshu University Hospital /ID# 213853
state: Nagano
city: Nagano-shi
country: Japan
facility: Nagano Red Cross Hospital /ID# 214572
state: Nagano
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center /ID# 213687
state: Saitama
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital /ID# 216347
state: Tokyo
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital /ID# 211692
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: KonKuk University Medical Center /ID# 213410
state: Seoul Teugbyeolsi
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital /ID# 211695
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital /ID# 211691
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 211740
city: Mexico City
country: Mexico
facility: RM Pharma Specialists S.A de C.V. /ID# 211879
state: Ciudad De Mexico
city: Mexico City
country: Mexico
facility: CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 211875
state: Ciudad De Mexico
city: Leon
country: Mexico
facility: Morales Vargas Centro de Investigacion S.C. /ID# 212946
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Centro Integral en Reumatologia S.A de C.V /ID# 211876
state: Jalisco
city: Guadalajara
country: Mexico
facility: Centro de Estudios de Investigación Básica y Clínica, S.C. /ID# 212532
state: Jalisco
city: San Luis Potosí
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación del Potosí, SC /ID# 212737
state: San Luis Potosi
city: Mérida
country: Mexico
facility: Medical Care & Research SA de CV /ID# 212682
state: Yucatan
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum /ID# 214424
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum /ID# 214413
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 214415
city: Papatoetoe
country: New Zealand
facility: Middlemore Clinical Trials /ID# 213504
state: Auckland
city: Takapuna
country: New Zealand
facility: North Shore Hospital /ID# 213506
state: Auckland
city: Hamilton
country: New Zealand
facility: Waikato Hospital /ID# 213505
state: Waikato
city: Wroclaw
country: Poland
facility: WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 212482
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o. /ID# 212146
state: Malopolskie
city: Warsaw
country: Poland
facility: Centrum Medyczne Pratia Warszawa /ID# 218176
state: Mazowieckie
city: Poznan
country: Poland
facility: Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im. Wiktora Degi /ID# 212483
state: Wielkopolskie
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC /ID# 211251
city: San Juan
country: Puerto Rico
facility: Mindful Medical Research /ID# 213384
city: Vitoria
country: Spain
facility: HUA - Txagorritxu /ID# 212520
state: Alava
city: Sabadell
country: Spain
facility: Consorci Corporacio Sanitaria Parc Tauli Sabadell /ID# 212145
state: Barcelona
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto /ID# 212722
state: Vizcaya
city: Galdakao
country: Spain
facility: Hospital Universitario de Galdakao /ID# 212803
state: Vizcaya
city: A Coruna
country: Spain
facility: Hospital Universitario A Coruna - CHUAC /ID# 211719
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 211757
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme /ID# 212721
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 211720
city: Taichung City
country: Taiwan
facility: China Medical University Hospital /ID# 212179
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital /ID# 211957
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 211752
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital /ID# 221600
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 212216
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 211751
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust /ID# 211931
state: London, City Of
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust /ID# 213189
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust /ID# 211838
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
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.