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: Upadacitinib; Drug: Placebo for Upadacitinib; Drug: Placebo for Elsubrutinib

• 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, 1046
      • 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
  • Urumqi, China, 830001
    • People's Hospital of Xinjiang /ID# 222928
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital /ID# 222950
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital /ID# 222851
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital, Fudan University /ID# 222929
• Colombia
  • Medellin, Colombia, 050034
    • Clinica Universitaria Bolivari /ID# 221880
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 80002
      • Centro Integral de Reumatologia del Caribe Circaribe SAS /ID# 221879
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110221
      • Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 221884
    • Chia, Cundinamarca, Colombia, 250001
      • Preventive Care Sas /Id# 221881
    • Zipaquira, Cundinamarca, Colombia, 250252
      • Healthy Medical Center SAS /ID# 221882
• Germany
  • Berlin, Germany, 10117
    • 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
      • Debreceni Egyetem Klinikai Kozpont /ID# 222480
  • Veszprem
    • Veszprém, Veszprem, Hungary, 8200
      • Vital Medicina Kft /ID# 222479
• Italy
  • Ferrara
    • Cona, Ferrara, Italy, 44124
      • 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, 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
    • 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, 40705
    • Taichung Veterans General Hospital /ID# 221748
  • Taichung, Taiwan, 40447
    • China Medical University Hospital /ID# 221747
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 221746
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital /ID# 221745
  • Taipei City, Taiwan, 11031
    • Taipei Medical University Hospital /ID# 227653
  • Taoyuan City, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital /ID# 222469
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • 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
      • 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
      • 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
      • 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Elsubrutinib Dose A and Upadacitinib Dose A; Participants will receive Elsubrutinib Dose A and Upadacitinib Dose A once daily (QD).	Drug: Elsubrutinib; Oral; Capsule; Other Names: ABBV-105; Drug: Upadacitinib; Oral; Tablet; Other Names: RINVOQ; ABT-494
Experimental: Part 2: Elsubrutinib Dose A and Upadacitinib Dose B; Participants will receive Elsubrutinib Dose A and Upadacitinib Dose B QD.	Drug: Elsubrutinib; Oral; Capsule; Other Names: ABBV-105; Drug: Upadacitinib; Oral; Tablet; Other Names: RINVOQ; ABT-494
Experimental: Part 3: Elsubrutinib Dose A and Upadacitinib Placebo; Participants will receive Elsubrutinib Dose A and Upadacitinib placebo QD.	Drug: Elsubrutinib; Oral; Capsule; Other Names: ABBV-105; Drug: Placebo for Upadacitinib; Oral; Tablet
Experimental: Part 4: Elsubrutinib Placebo and Upadacitinib Dose A; Participants will receive Elsubrutinib placebo and Upadacitinib Dose A QD.	Drug: Upadacitinib; Oral; Tablet; Other Names: RINVOQ; ABT-494; Drug: Placebo for Elsubrutinib; Oral; Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 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 any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.	Through Week 108

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4	SRI is a composite responder index based on improvement in disease activity without worsening of the overall condition or the development of significant disease activity in new organ systems.	Through Week 104
Achievement of British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA)	BICLA is a composite responder index based on improvement in organ systems without worsening of the overall condition and improvement in disease activity.	Through Week 104
Change in Steroid Burden	Steroid Burden is measured as milligrams (mg) of prednisone-equivalent administered.	Baseline of M19-130 (Week 0) Through Week 104
Number of Flares Per Patient-Year (Respectively and Overall) by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI) flare index (SFI)	SELENA SLEDAI flare index defines (mild, moderate or severe) SLE flares using the SLEDAI-2K score, disease activity scenarios, treatment changes, and Physician's Global Assessment of Disease Activity.	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): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 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: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus 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