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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03978520




Registration number
NCT03978520
Ethics application status
Date submitted
3/06/2019
Date registered
7/06/2019
Date last updated
21/07/2023

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2019-000638-20
Secondary ID [2] 0 0
M19-130
Universal Trial Number (UTN)
Trial acronym
SLEek
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus (SLE) 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Elsubrutinib
Treatment: Drugs - Placebo for elsubrutinib
Treatment: Drugs - Upadacitinib
Treatment: Drugs - Placebo for upadacitinib

Placebo comparator: Elsubrutinib placebo/upadacitinib placebo - Placebo capsule for elsubrutinib once a day by mouth for up to 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for up to 48 weeks

Experimental: ABBV-599 High Dose (Elsubrutinib 60 mg/upadacitinib 30 mg) - 60 mg elsubrutinib capsule once a day by mouth for up to 48 weeks; 30 mg upadacitinib film-coated tablet once a day by mouth for up to 48 weeks

Experimental: Elsubrutinib placebo/upadacitinib 30 mg - Placebo capsule for elsubrutinib once a day by mouth for up to 48 weeks; 30 mg upadacitinib film-coated tablet once a day by mouth for up to 48 weeks

Experimental: ABBV-599 Low Dose (Elsubrutinib 60 mg/upadacitinib 15 mg) - 60 mg elsubrutinib capsule once a day by mouth for up to 24 weeks; 15 mg upadacitinib film-coated tablet once a day by mouth for up to 24 weeks

Experimental: Elsubrutinib 60 mg/upadacitinib placebo - 60 mg elsubrutinib capsule once a day by mouth for up to 24 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for up to 24 weeks


Treatment: Drugs: Elsubrutinib
Capsule; Oral

Treatment: Drugs: Placebo for elsubrutinib
Capsule; Oral

Treatment: Drugs: Upadacitinib
Film-coated tablet; Oral

Treatment: Drugs: Placebo for upadacitinib
Film-coated tablet; Oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving SLE Responder Index (SRI)-4 and Steroid Dose = 10 mg Prednisone Equivalent Once a Day (QD) at Week 24
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Percentage of Participants Achieving SLE Responder Index (SRI)-4 at Week 24
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG) Based Combined Lupus Assessment (BICLA) Response at Week 24
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 24
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Change From Baseline in Daily Prednisone Dose at Week 24
Timepoint [4] 0 0
From Baseline to Week 24
Secondary outcome [5] 0 0
Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Flare Index Through Week 24
Timepoint [5] 0 0
From Baseline to Week 24

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/07/2022
Sample size
Target
Accrual to date
Final
341
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Emeritus Research Sydney /ID# 222983 - Botany
Recruitment hospital [2] 0 0
Royal North Shore Hospital /ID# 222982 - St Leonards
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital /ID# 212667 - Herston
Recruitment hospital [4] 0 0
Rheumatology Research Unit Sunshine Coast /ID# 211902 - Maroochydore
Recruitment hospital [5] 0 0
Griffith University /ID# 223543 - Southport
Recruitment hospital [6] 0 0
The Queen Elizabeth Hospital /ID# 211901 - Woodville South
Recruitment hospital [7] 0 0
Emeritus Research /ID# 211903 - Camberwell
Recruitment hospital [8] 0 0
Monash Medical Centre /ID# 212313 - Clayton
Recruitment hospital [9] 0 0
St Vincent's Hospital Melbourne /ID# 212311 - Fitzroy Melbourne
Recruitment postcode(s) [1] 0 0
2019 - Botany
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4558 - Maroochydore
Recruitment postcode(s) [5] 0 0
4222 - Southport
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment postcode(s) [7] 0 0
3124 - Camberwell
Recruitment postcode(s) [8] 0 0
3168 - Clayton
Recruitment postcode(s) [9] 0 0
3065 - Fitzroy Melbourne
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT03978520
Trial related presentations / publications
Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03978520