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)

Systemic Lupus Erythematosus (SLE) Clinical Trial

— SLEek  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03978520
• Other study ID #: M19-130
• Secondary ID: 2019-000638-20
• Status: Completed
• Phase: Phase 2
• Start date: July 25, 2019
• Est. completion date: July 14, 2022

Study information

• Verified date: June 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 341
• Est. completion date: July 14, 2022
• Est. primary completion date: January 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus (SLE)

Intervention

Drug:
• Elsubrutinib
Capsule; Oral
• Placebo for elsubrutinib
Capsule; Oral
• Upadacitinib
Film-coated tablet; Oral
• Placebo for upadacitinib
Film-coated tablet; Oral

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Canada,  China,  Colombia,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Puerto Rico,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving SLE Responder Index (SRI)-4 and Steroid Dose = 10 mg Prednisone Equivalent Once a Day (QD) at Week 24	SLE Responder Index (SRI)-4 is defined as follows with all criteria compared to Baseline: = 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, Week 24
Secondary	Percentage of Participants Achieving SLE Responder Index (SRI)-4 at Week 24	SLE Responder Index (SRI)-4 is defined as follows with all criteria compared to Baseline: = 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, Week 24
Secondary	Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG) Based Combined Lupus Assessment (BICLA) Response at Week 24	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, Week 24
Secondary	Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 24	LLDAS is a state of low disease activity based on Systemic Lupus Erythematosus Disease Activity Index 2000 score (SLEDAI-2K score =4 excluding SLEDAI-2K activity in major organ systems), absence of SLE disease activity in major organ systems and new disease activity, Physician's Global Assessment (PhGA =1), and concomitant medication usage (steroid dose =7.5 mg QD and toleration of immunosuppressive drugs at standard maintenance doses).	Baseline, Week 24
Secondary	Change From Baseline in Daily Prednisone Dose at Week 24	Participants' current use of steroid therapy was assessed at each study visit, and the amount of daily prednisone was documented.	From Baseline to Week 24
Secondary	Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Flare Index Through Week 24	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 Baseline to Week 24

External Links

•   This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.