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NCT03978520: SLEek

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)

Completed Phase 2 Results posted Last updated 21 July 2023
What this trial tests

Phase 2 trial testing Elsubrutinib in Systemic Lupus Erythematosus (SLE) in 341 participants. Completed in 14 July 2022.

Timeline
25 July 2019
Primary endpoint
19 January 2022
14 July 2022

Quick facts

Lead sponsorAbbVie
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment341
Start date25 July 2019
Primary completion19 January 2022
Estimated completion14 July 2022
Sites160 locations across Italy, Colombia, Japan, Taiwan, Poland, South Korea, New Zealand, Netherlands

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 65, any sex, with Systemic Lupus Erythematosus (SLE). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving SLE Responder Index (SRI)-4 and Steroid Dose ≤ 10 mg Prednisone Equivalent Once a Day (QD) at Week 24 Primary · Baseline, 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 indicati

GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo37.326.4 – 48.3
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)48.536.7 – 60.4
Elsubrutinib Placebo/Upadacitinib 30 mg54.842.5 – 67.2
Percentage of Participants Achieving SLE Responder Index (SRI)-4 at Week 24 Secondary · Baseline, 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 indicati

GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo38.727.6 – 49.7
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)54.442.6 – 66.2
Elsubrutinib Placebo/Upadacitinib 30 mg56.544.1 – 68.8
Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG) Based Combined Lupus Assessment (BICLA) Response at Week 24 Secondary · Baseline, 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.

GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo42.731.5 – 53.9
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)54.442.6 – 66.2
Elsubrutinib Placebo/Upadacitinib 30 mg58.145.8 – 70.3
Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 24 Secondary · Baseline, 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).

GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo13.35.6 – 21.0
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)30.919.9 – 41.9
Elsubrutinib Placebo/Upadacitinib 30 mg45.232.8 – 57.5
Change From Baseline in Daily Prednisone Dose at Week 24 Secondary · From Baseline to Week 24

Participants' current use of steroid therapy was assessed at each study visit, and the amount of daily prednisone was documented.

GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo-0.65-1.57 – 0.28
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)-0.45-1.38 – 0.48
Elsubrutinib Placebo/Upadacitinib 30 mg-0.62-1.60 – 0.36
Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Flare Index Through Week 24 Secondary · From Baseline to 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.

Mild/Moderate
GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo2.451.92 – 2.99
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)1.390.97 – 1.81
Elsubrutinib Placebo/Upadacitinib 30 mg1.761.28 – 2.25
Severe
GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo0.360.16 – 0.56
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)0.260.08 – 0.44
Elsubrutinib Placebo/Upadacitinib 30 mg0.10-0.01 – 0.22
Overall
GroupValue95% CI
Elsubrutinib Placebo/Upadacitinib Placebo2.812.24 – 3.38
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)1.651.20 – 2.10
Elsubrutinib Placebo/Upadacitinib 30 mg1.871.37 – 2.36

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality is reported from enrollment to end of study; median time on follow-up was 337.0 days, 337.0 days, 338.5 days, 281.0 days, and 295.0 days for the placebo, ABBV-599 High Dose, upadacitinib, ABBV-599 Low Dose, and elsubrutinib groups, respectively.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Elsubrutinib Placebo/Upadacitinib Placebo
Serious: 13/75 (17%)
Deaths: 0/75
ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg)
Serious: 7/68 (10%)
Deaths: 2/68
Elsubrutinib Placebo/Upadacitinib 30 mg
Serious: 13/62 (21%)
Deaths: 0/62
ABBV-599 Low Dose (Elsubrutinib 60 mg/Upadacitinib 15 mg)
Serious: 9/69 (13%)
Deaths: 0/69
Elsubrutinib 60 mg/Upadacitinib Placebo
Serious: 7/67 (10%)
Deaths: 2/67

Serious adverse events (55 terms)

ReactionSystemElsubrutinib Placebo/Upada…ABBV-599 High Dose (Elsubr…Elsubrutinib Placebo/Upada…ABBV-599 Low Dose (Elsubru…Elsubrutinib 60 mg/Upadaci…
PNEUMONIAInfections and infestations
SYSTEMIC LUPUS ERYTHEMATOSUSMusculoskeletal and connective tissue disorders
URETEROLITHIASISRenal and urinary disorders
ABORTION INDUCEDSurgical and medical procedures
NEUTROPENIABlood and lymphatic system disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
ACUTE MYOCARDIAL INFARCTIONCardiac disorders
PERICARDIAL EFFUSIONCardiac disorders
STRESS CARDIOMYOPATHYCardiac disorders
DYSPHAGIAGastrointestinal disorders
GASTRITISGastrointestinal disorders
OESOPHAGITISGastrointestinal disorders
ACCIDENTAL DEATHGeneral disorders
ABSCESS LIMBInfections and infestations
COVID-19Infections and infestations
COVID-19 PNEUMONIAInfections and infestations
DISSEMINATED VARICELLA ZOSTER VIRUS INFECTIONInfections and infestations
DIVERTICULITISInfections and infestations
ENDOCARDITIS BACTERIALInfections and infestations
ESCHERICHIA SEPSISInfections and infestations
GASTROENTERITISInfections and infestations
GASTROENTERITIS VIRALInfections and infestations
HERPES ZOSTERInfections and infestations
MENINGITIS TUBERCULOUSInfections and infestations
MYCOPLASMA INFECTIONInfections and infestations
Other adverse events (20 terms — click to expand)

ReactionSystemElsubrutinib Placebo/Upada…ABBV-599 High Dose (Elsubr…Elsubrutinib Placebo/Upada…ABBV-599 Low Dose (Elsubru…Elsubrutinib 60 mg/Upadaci…
URINARY TRACT INFECTIONInfections and infestations
HEADACHENervous system disorders
COVID-19Infections and infestations
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
HERPES ZOSTERInfections and infestations
DIARRHOEAGastrointestinal disorders
NAUSEAGastrointestinal disorders
PYREXIAGeneral disorders
NASOPHARYNGITISInfections and infestations
ORAL HERPESInfections and infestations
ARTHRALGIAMusculoskeletal and connective tissue disorders
CONSTIPATIONGastrointestinal disorders
GASTRITISGastrointestinal disorders
VOMITINGGastrointestinal disorders
FATIGUEGeneral disorders
BRONCHITISInfections and infestations
WEIGHT INCREASEDInvestigations
BACK PAINMusculoskeletal and connective tissue disorders
INSOMNIAPsychiatric disorders
ACNESkin and subcutaneous tissue disorders

Most-reported serious reactions: PNEUMONIA, SYSTEMIC LUPUS ERYTHEMATOSUS, URETEROLITHIASIS, ABORTION INDUCED, NEUTROPENIA, THROMBOCYTOPENIA, ACUTE MYOCARDIAL INFARCTION, PERICARDIAL EFFUSION.

Data from ClinicalTrials.gov NCT03978520 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach.
    Tanaka Y, Luo Y, O'Shea JJ, Nakayamada S. · · 2022 · cited 329× · PMID 34987201 · DOI 10.1038/s41584-021-00726-8
  2. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens.
    Hu Q, Bian Q, Rong D, Wang L, et al · · 2023 · cited 190× · PMID 36911202 · DOI 10.3389/fbioe.2023.1110765
  3. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  4. Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures.
    Ringheim GE, Wampole M, Oberoi K. · · 2021 · cited 100× · PMID 34803999 · DOI 10.3389/fimmu.2021.662223
  5. New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond.
    Demirkaya E, Sahin S, Romano M, Zhou Q, et al · · 2020 · cited 98× · PMID 32151092 · DOI 10.3390/jcm9030712
  6. Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story.
    Bonelli M, Kerschbaumer A, Kastrati K, Ghoreschi K, et al · · 2024 · cited 95× · PMID 37923366 · DOI 10.1136/ard-2023-223850
  7. JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition.
    Luo Y, Alexander M, Gadina M, O'Shea JJ, et al · · 2021 · cited 92× · PMID 34625141 · DOI 10.1016/j.jaci.2021.08.004
  8. BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.
    Alu A, Lei H, Han X, Wei Y, et al · · 2022 · cited 88× · PMID 36183125 · DOI 10.1186/s13045-022-01353-w

Verify or expand the search:

Other trials of Elsubrutinib

Trials testing the same drug.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03978520.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing