Clinical trial NCT04451772: A Study of the Safety of Oral Elsubrutinib Capsules and Oral Upadacitinib Tablets Given Alone or in Combination (ABBV-599) for Adult Participants With Moderately to Severely Active Systemic Lupus Erythematosus to Assess Change in Disease State
Official title: A Phase 2, Long-Term Extension (LTE) Study With Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599) in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus Who Have Completed the M19-130 Phase 2 Randomized Controlled Trial (RCT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: Systemic Lupus Erythematosus
ABBV-599
ABBV-105
ABT-494
Elsubrutinib
Upadacitinib
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-06-30
Enrollment: 185
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: Systemic Lupus Erythematosus (SLE) is an immune-mediated disease associated with inflammation of multiple organ systems. This study will evaluate how well elsubrutinib and upadacitinib given alone or as the ABBV-599 combination (elsubrutinib/upadacitinib) works within the body, in participants who completed study M19-130. This study will assess the change in disease symptoms.

ABBV-599 is an investigational drug being developed for the treatment of Systemic Lupus Erythematosus (SLE). This study is "double-blinded", which means that neither the trial participants nor the study doctors will know who will be given which study drug. Study doctors put the participants into 1 of 4 groups called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of SLE will be enrolled. Around 260 participants will be enrolled in the study in approximately 100 sites worldwide.

Participants will receive the following for up to 56 weeks:

Participants will receive oral elsubrutinib capsules and/or oral upadacitinib tablets once daily for up to 56 weeks. Participants who were receiving elsubrutinib and/or upadacitnib in M19-130 will continue to receive the same treatment in this study. Participants who were receiving placebo in M19-130 will be re-randomized to one of the 2 combination treatment arms in this study.

Arm 1: Elsubrutinib Dose A and Upadacitinib Dose A Arm 2: Elsubrutinib Dose A and Upadacitinib Dose B

There may be higher burden for participants in this trial compared to their standard of care. Participants will attend monthly visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.


Eligibility criteria: Inclusion Criteria:

* Completed Study M19-130 (i.e., the randomized controlled trial of elsubrutinib, upadacitinib, and ABBV-599 \[elsubrutinib/upadacitinib\] combination or matching placebo) and will not have developed any laboratory or clinical discontinuation criteria as defined in that study.
* On stable background treatment for SLE throughout the study.

Exclusion Criteria:

* Active, chronic, or recurrent viral, or bacterial infection.
* Active tuberculosis (TB)
* History of gastrointestinal (GI) perforation, diverticulitis, or a significantly increased risk for GI perforation per investigator assessment.
* Participant require vaccination with live vaccine during study participation.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: From the first dose of study drug in Study M20-186 up to 30 days after the last dose of study drug, up to 442 days
Secondary outcomes:
measure: Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4
timeFrame: Baseline of Study M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104
measure: Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response
timeFrame: Baseline of Study M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104
measure: Change From Baseline in Daily Prednisone Dose Over Time
timeFrame: Baseline of M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104
measure: Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI) Flare Index Through Week 104
timeFrame: From Week 56 through Week 104
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Duplicate_AZ Arthritis and Rheumotology Research, PLLC /ID# 227833
state: Arizona
city: Beverly Hills
country: United States
facility: Wallace Rheumatic Studies Center, LLC /ID# 224374
state: California
city: Los Alamitos
country: United States
facility: Valerius Medical Group & Research Center /ID# 223922
state: California
city: San Leandro
country: United States
facility: East Bay Rheumatology Medical /ID# 225493
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital /ID# 245087
state: Colorado
city: Aventura
country: United States
facility: Duplicate_Arthritis & Rheumatic Disease Specialties /ID# 227828
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research /ID# 233192
state: Florida
city: Plantation
country: United States
facility: IRIS Research and Development, LLC /ID# 227814
state: Florida
city: Libertyville
country: United States
facility: Deerbrook Medical Associates /ID# 227330
state: Illinois
city: Evansville
country: United States
facility: Qualmedica Research, LLC /ID# 227817
state: Indiana
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research /ID# 225479
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 222505
state: Massachusetts
city: Lansing
country: United States
facility: June DO, PC /ID# 221841
state: Michigan
city: New York
country: United States
facility: Duplicate_NYU Langone Health/NYU School of Medicine /ID# 245088
state: New York
city: Vandalia
country: United States
facility: STAT Research, Inc. /ID# 221840
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Health Network Research Institute /ID# 245086
state: Pennsylvania
city: Memphis
country: United States
facility: Dr. Ramesh Gupta /ID# 225524
state: Tennessee
city: Austin
country: United States
facility: Tekton Research, Inc. /ID# 224411
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Management /ID# 225509
state: Texas
city: Mesquite
country: United States
facility: SW Rheumatology Res. LLC /ID# 225485
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic /ID# 227832
state: Virginia
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich /ID# 222569
state: Buenos Aires
city: La Plata
country: Argentina
facility: Hospital Interzonal General de Agudos General Jose de San Martin /ID# 221893
state: Buenos Aires
city: Quilmes
country: Argentina
facility: CER Instituto Medico /ID# 223175
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Aprillus Asistencia e Investigacion /ID# 221890
state: Ciudad Autonoma De Buenos Aires
city: Rosario
country: Argentina
facility: Instituto CAICI S.R.L /ID# 221892
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Medicas Tucuman /ID# 221888
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones Clinicas Tucuman /ID# 221889
state: Tucuman
city: Maroochydore
country: Australia
facility: Rheumatology Research Unit Sunshine Coast /ID# 221816
state: Queensland
city: Camberwell
country: Australia
facility: Emeritus Research /ID# 223027
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre /ID# 221814
state: Victoria
city: Sofia
country: Bulgaria
facility: UMHAT Sveti Ivan Rilski /ID# 223358
city: Sofia
country: Bulgaria
facility: UMHAT Sveti Ivan Rilski /ID# 223359
city: Beijing
country: China
facility: Duplicate_Peking Union Medical College Hospital /ID# 222950
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital /ID# 222851
state: Guangdong
city: Urumqi
country: China
facility: People's Hospital of Xinjiang /ID# 222928
state: Guizhou
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University /ID# 222929
state: Shanghai
city: Barranquilla
country: Colombia
facility: Duplicate_Centro Integral de Reumatologia del Caribe Circaribe SAS /ID# 221879
state: Atlantico
city: Bogota
country: Colombia
facility: Duplicate_Centro de Investigacion en Reumatologia y Especialidades Medicas- CIRE /ID# 221884
state: Cundinamarca
city: Chia
country: Colombia
facility: Preventive Care Sas /Id# 221881
state: Cundinamarca
city: Zipaquirá
country: Colombia
facility: Healthy Medical Center S.A.S /ID# 221882
state: Cundinamarca
city: Medellin
country: Colombia
facility: Clinica Universitaria Bolivari /ID# 221880
state: Valle Del Cauca
city: Berlin
country: Germany
facility: Duplicate_Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 222963
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 222964
city: Debrecen
country: Hungary
facility: Duplicate_Debreceni Egyetem Klinikai Kozpont /ID# 222480
state: Hajdu-Bihar
city: Veszprém
country: Hungary
facility: Vital Medicina Kft /ID# 222479
state: Veszprem
city: Cona
country: Italy
facility: Duplicate_Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant Anna /ID# 221919
state: Ferrara
city: Nagoya-shi
country: Japan
facility: Chukyo Hospital /ID# 223398
state: Aichi
city: Nagoya-shi
country: Japan
facility: NHO Nagoya Medical Center /ID# 222397
state: Aichi
city: Kitakyushu-shi
country: Japan
facility: Hospital of the University of Occupational and Environmental Health, Japan /ID# 222499
state: Fukuoka
city: Hiroshima-shi
country: Japan
facility: Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 222393
state: Hiroshima
city: Asahikawa-shi
country: Japan
facility: National Hospital Organization Asahikawa Medical Center /ID# 222394
state: Hokkaido
city: Kagoshima-shi
country: Japan
facility: EIRAKU Internal Medicine Clinic /ID# 222385
state: Kagoshima
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 222392
state: Miyagi
city: Matsumoto-shi
country: Japan
facility: Shinshu University Hospital /ID# 222395
state: Nagano
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center /ID# 222389
state: Saitama
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital /ID# 222498
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 221897
state: Seoul Teugbyeolsi
city: Mexico City
country: Mexico
facility: RM Pharma Specialists S.A de C.V. /ID# 221915
state: Ciudad De Mexico
city: Mexico City
country: Mexico
facility: CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 221913
state: Ciudad De Mexico
city: Leon
country: Mexico
facility: Morales Vargas Centro de Investigacion S.C. /ID# 221912
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Centro Integral en Reumatologia S.A de C.V /ID# 221914
state: Jalisco
city: Guadalajara
country: Mexico
facility: Centro de Estudios de Investigación Básica y Clínica, S.C. /ID# 221910
state: Jalisco
city: Mérida
country: Mexico
facility: Medical Care & Research SA de CV /ID# 221911
state: Yucatan
city: Takapuna
country: New Zealand
facility: North Shore Hospital /ID# 221850
state: Auckland
city: Wroclaw
country: Poland
facility: WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 221860
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o. /ID# 224430
state: Malopolskie
city: Warszawa
country: Poland
facility: MTZ Clinical Research Powered by Pratia /ID# 224431
state: Mazowieckie
city: Poznan
country: Poland
facility: Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im. Wiktora Degi /ID# 221859
state: Wielkopolskie
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC /ID# 224394
city: San Juan
country: Puerto Rico
facility: Mindful Medical Research /ID# 222513
city: Vitoria
country: Spain
facility: HUA - Txagorritxu /ID# 221992
state: Alava
city: Sabadell
country: Spain
facility: Consorci Corporacio Sanitaria Parc Tauli Sabadell /ID# 221995
state: Barcelona
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto /ID# 221999
state: Vizcaya
city: Galdakao
country: Spain
facility: Hospital Universitario de Galdakao /ID# 221996
state: Vizcaya
city: A Coruna
country: Spain
facility: Duplicate_Hospital Universitario A Coruna - CHUAC /ID# 221993
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 221994
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme /ID# 221997
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 221998
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital /ID# 221748
state: Keelung
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 221746
state: Keelung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 221745
state: Taipei
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 221747
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital /ID# 227653
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 222469
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust /ID# 221863
state: London, City Of
city: Manchester
country: United Kingdom
facility: Duplicate_Manchester University NHS Foundation Trust /ID# 221861
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: