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

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)

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: Elsubrutinib; Drug: Placebo for Elsubrutinib; Drug: Upadacitinib; Drug: Placebo for Upadacitinib

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, 1426
      • Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich /ID# 222569
    • La Plata, Buenos Aires, Argentina, 1900
      • Hospital Interzonal General de Agudos General Jose de San Martin /ID# 221893
    • Quilmes, Buenos Aires, Argentina, 1878
      • CER Instituto Medico /ID# 223175
  • Ciudad Autonoma De Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Ciudad Autonoma De Buenos Aires, Argentina, 1958
      • Aprillus Asistencia e Investigacion /ID# 221890
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Instituto CAICI S.R.L /ID# 221892
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Centro de Investigaciones Medicas Tucuman /ID# 221888
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Investigaciones Clinicas Tucuman /ID# 221889
• Australia
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Rheumatology Research Unit Sunshine Coast /ID# 221816
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research /ID# 223027
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre /ID# 221814
• Bulgaria
  • Sofia, Bulgaria, 1431
    • UMHAT Sveti Ivan Rilski /ID# 223358
  • Sofia, Bulgaria, 1431
    • UMHAT Sveti Ivan Rilski /ID# 223359
• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Duplicate_Peking Union Medical College Hospital /ID# 222950
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital /ID# 222851
  • Guizhou
    • Urumqi, Guizhou, China, 830001
      • People's Hospital of Xinjiang /ID# 222928
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital, Fudan University /ID# 222929
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 80002
      • Duplicate_Centro Integral de Reumatologia del Caribe Circaribe SAS /ID# 221879
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110221
      • Duplicate_Centro de Investigacion en Reumatologia y Especialidades Medicas- CIRE /ID# 221884
    • Chia, Cundinamarca, Colombia, 250001
      • Preventive Care Sas /Id# 221881
    • Zipaquirá, Cundinamarca, Colombia, 250252
      • Healthy Medical Center S.A.S /ID# 221882
  • Valle Del Cauca
    • Medellin, Valle Del Cauca, Colombia, 050034
      • Clinica Universitaria Bolivari /ID# 221880
• Germany
  • Berlin, Germany, 10117
    • Duplicate_Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 222963
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 222964
• Hungary
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary, 4032
      • Duplicate_Debreceni Egyetem Klinikai Kozpont /ID# 222480
  • Veszprem
    • Veszprém, Veszprem, Hungary, 8200
      • Vital Medicina Kft /ID# 222479
• Italy
  • Ferrara
    • Cona, Ferrara, Italy, 44124
      • Duplicate_Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant Anna /ID# 221919
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 457-8510
      • Chukyo Hospital /ID# 223398
    • Nagoya-shi, Aichi, Japan, 460-0001
      • NHO Nagoya Medical Center /ID# 222397
  • Fukuoka
    • Kitakyushu-shi, Fukuoka, Japan, 807-8556
      • Hospital of the University of Occupational and Environmental Health, Japan /ID# 222499
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 730-8619
      • Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 222393
  • Hokkaido
    • Asahikawa-shi, Hokkaido, Japan, 070-8644
      • National Hospital Organization Asahikawa Medical Center /ID# 222394
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 890-0063
      • EIRAKU Internal Medicine Clinic /ID# 222385
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 9808574
      • Tohoku University Hospital /ID# 222392
  • Nagano
    • Matsumoto-shi, Nagano, Japan, 390-8621
      • Shinshu University Hospital /ID# 222395
  • Saitama
    • Kawagoe-shi, Saitama, Japan, 350-8550
      • Saitama Medical Center /ID# 222389
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital /ID# 222498
• Korea, Republic of
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
      • Seoul National University Hospital /ID# 221897
• Mexico
  • Ciudad De Mexico
    • Mexico City, Ciudad De Mexico, Mexico, 03100
      • RM Pharma Specialists S.A de C.V. /ID# 221915
    • Mexico City, Ciudad De Mexico, Mexico, 11850
      • CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 221913
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37000
      • Morales Vargas Centro de Investigacion S.C. /ID# 221912
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Centro Integral en Reumatologia S.A de C.V /ID# 221914
    • Guadalajara, Jalisco, Mexico, 44690
      • Centro de Estudios de Investigación Básica y Clínica, S.C. /ID# 221910
  • Yucatan
    • Mérida, Yucatan, Mexico, 97070
      • Medical Care & Research SA de CV /ID# 221911
• New Zealand
  • Auckland
    • Takapuna, Auckland, New Zealand, 0622
      • North Shore Hospital /ID# 221850
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 51-685
      • WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 221860
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-011
      • Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o. /ID# 224430
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-172
      • MTZ Clinical Research Powered by Pratia /ID# 224431
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 61-545
      • Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im. Wiktora Degi /ID# 221859
• Puerto Rico
  • San Juan, Puerto Rico, 00917-3104
    • GCM Medical Group PSC /ID# 224394
  • San Juan, Puerto Rico, 00918-3756
    • Mindful Medical Research /ID# 222513
• Spain
  • A Coruna, Spain, 15006
    • Duplicate_Hospital Universitario A Coruna - CHUAC /ID# 221993
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 221994
  • Sevilla, Spain, 41014
    • Hospital Universitario Virgen de Valme /ID# 221997
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe /ID# 221998
  • Alava
    • Vitoria, Alava, Spain, 01009
      • HUA - Txagorritxu /ID# 221992
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Consorci Corporacio Sanitaria Parc Tauli Sabadell /ID# 221995
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital Universitario Basurto /ID# 221999
    • Galdakao, Vizcaya, Spain, 48960
      • Hospital Universitario de Galdakao /ID# 221996
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital /ID# 221747
  • Taipei City, Taiwan, 11031
    • Taipei Medical University Hospital /ID# 227653
  • Taoyuan City, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital /ID# 222469
  • Keelung
    • Taichung, Keelung, Taiwan, 40705
      • Taichung Veterans General Hospital /ID# 221748
    • Taipei, Keelung, Taiwan, 11217
      • Taipei Veterans General Hosp /ID# 221746
  • Taipei
    • Taipei City, Taipei, Taiwan, 100
      • National Taiwan University Hospital /ID# 221745
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Duplicate_Manchester University NHS Foundation Trust /ID# 221861
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guys and St Thomas NHS Foundation Trust /ID# 221863
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032-9306
      • Duplicate_AZ Arthritis and Rheumotology Research, PLLC /ID# 227833
  • California
    • Beverly Hills, California, United States, 90211
      • Wallace Rheumatic Studies Center, LLC /ID# 224374
    • Los Alamitos, California, United States, 90720-5402
      • Valerius Medical Group & Research Center /ID# 223922
    • San Leandro, California, United States, 94578
      • East Bay Rheumatology Medical /ID# 225493
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital /ID# 245087
  • Florida
    • Aventura, Florida, United States, 33180
      • Duplicate_Arthritis & Rheumatic Disease Specialties /ID# 227828
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research /ID# 233192
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development, LLC /ID# 227814
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • Deerbrook Medical Associates /ID# 227330
  • Indiana
    • Evansville, Indiana, United States, 47714-0805
      • Qualmedica Research, LLC /ID# 227817
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research /ID# 225479
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center /ID# 222505
  • Michigan
    • Lansing, Michigan, United States, 48911
      • June DO, PC /ID# 221841
  • New York
    • New York, New York, United States, 10016-2772
      • Duplicate_NYU Langone Health/NYU School of Medicine /ID# 245088
  • Ohio
    • Vandalia, Ohio, United States, 45377-9464
      • STAT Research, Inc. /ID# 221840
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Allegheny Health Network Research Institute /ID# 245086
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Dr. Ramesh Gupta /ID# 225524
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc. /ID# 224411
    • Houston, Texas, United States, 77084
      • Accurate Clinical Management /ID# 225509
    • Mesquite, Texas, United States, 75150
      • SW Rheumatology Res. LLC /ID# 225485
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Carilion Clinic /ID# 227832

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABBV-599 High Dose (Elsubrutinib 60 mg/upadacitinib 30 mg) -> ABBV-599 High Dose; Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.	Drug: Elsubrutinib; Capsule; Oral; Other Names: ABBV-105; Drug: Upadacitinib; Film-coated tablet; Oral; Other Names: RINVOQ; ABT-494
Experimental: Elsubrutinib placebo/upadacitinib 30 mg -> Elsubrutinib placebo/upadacitinib 30 mg; Participants received placebo capsules for elsubrutinib once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.	Drug: Placebo for Elsubrutinib; Capsule; Oral; Drug: Upadacitinib; Film-coated tablet; Oral; Other Names: RINVOQ; ABT-494
Experimental: Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 High Dose; Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day in the current study (M20-186) for up to 56 weeks.	Drug: Elsubrutinib; Capsule; Oral; Other Names: ABBV-105; Drug: Upadacitinib; Film-coated tablet; Oral; Other Names: RINVOQ; ABT-494
Experimental: ABBV-599 Low Dose (Elsubrutinib 60 mg/upadacitinib 15 mg) -> ABBV-599 Low Dose; Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.	Drug: Elsubrutinib; Capsule; Oral; Other Names: ABBV-105; Drug: Upadacitinib; Film-coated tablet; Oral; Other Names: RINVOQ; ABT-494
Experimental: Elsubrutinib 60 mg/upadacitinib placebo -> Elsubrutinib 60 mg/upadacitinib placebo; Participants received elsubrutinib 60 mg capsules once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.	Drug: Elsubrutinib; Capsule; Oral; Other Names: ABBV-105; Drug: Placebo for Upadacitinib; Film-coated tablet; Oral
Experimental: Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 Low Dose; Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in the current study (M20-186) for up to 56 weeks.	Drug: Elsubrutinib; Capsule; Oral; Other Names: ABBV-105; Drug: Upadacitinib; Film-coated tablet; Oral; Other Names: RINVOQ; ABT-494

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs) are defined as an adverse event with an onset date that is on or after the first dose of study drug from Study M20-186, and no more than 30 days after the last dose of study drug from Study M20-186. For more details on adverse events please see the Adverse Event section.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4	SLE Responder Index (SRI)-4 is defined as follows with all criteria compared to Baseline in Study M19-130: ≥4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; No worsening of the overall condition (< 0.3 point increase in Physician's Global Assessment [PhGA]); No new British Isles Lupus Assessment Group (BILAG) A or more than 1 new BILAG B disease activity scores (i.e., no organ system changes from baseline B/C/D/E to A and no more than 1 organ system changes from baseline C/D/E to B). A letter score is assigned to each organ system with following indications: A = severe, B = moderate, C = mild, D = inactive with prior history, and E = inactive with no history.	Baseline of Study M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104
Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response	BICLA is a composite responder index. Achievement of BICLA response is defined as improvement in all initial A and B BILAG scores, with no more than one new BILAG B score without worsening of the overall condition (no worsening in Physician's Global Assessment [PhGA], < 0.3 point increase) and no worsening of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score.	Baseline of Study M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104
Change From Baseline in Daily Prednisone Dose Over Time	Participants'current use of steroid therapy was assessed at each study visit, and the amount of daily prednisone was documented.	Baseline of M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104
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	The SELENA SLEDAI flare index defines mild/moderate or severe SLE flares using the SLEDAI score, definitions of worsening signs and symptoms, treatment changes, and Physician's Global Assessment of Disease Activity.	From Week 56 through Week 104

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Actual): January 3, 2024
• Study Completion (Actual): January 3, 2024

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Upadacitinib; Systemic Lupus Erythematosus; ABBV-599; ABBV-105; ABT-494; Elsubrutinib
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic; Janus Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: M20-186; 2020-001690-72 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes