A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599 Combination) in Subjects with Moderately to Severely Active Systemic Lupus Erythematosus

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2019-000638-20-BG
• Date of registration: 14/08/2020
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599 Combination) in Subjects with Moderately to Severely Active Systemic Lupus Erythematosus
• 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
• Date of first enrolment: 09/11/2020
• Target sample size: 325
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000638-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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, United States

Contacts

• Name: EU clinical trials helpdesk
• Affiliation: AbbVie Ltd.

• Name: EU clinical trials helpdesk
• Affiliation: AbbVie Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
• Adult male or female, 18 to 65 years of age, inclusive, at Screening.
•Clinical diagnosis of SLE at least 24 weeks prior to Screening, meeting at least 4 of the 11 ACR criteria OR meeting at least 4 of the SLICC criteria including at least 1 clinical and 1 immunologic criterion.
• At Screening, must have at least one of the following:
· ANA+ (titer = 1:80)
· anti-dsDNA+
· anti-Smith+
• SLEDAI-2K = 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 4 points of the required clinical score are for proteinuria attributable
to active lupus nephritis, it must be > 0.5 g/day equivalent (0.5
mg/mg).
· If subject has rash and PI considers it to be attributable to SLE, subject must consent to skin photograph collection for adjudication.
· Score must be re-confirmed at the Baseline Visit
•The subject must be on background treatment throughout the study. The background treatment must be 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 MTX
(= 20 mg).
· The combination of background treatment with antimalarial(s) and/or prednisone (or equivalent) is permitted.
· And a single, but not multiple, additional immunosuppressant from the list above, is permitted.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 315
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
• Women of childbearing potential must not have a positive serum pregnancy test at the screening visit and must have a negative urine pregnancy test at baseline prior to the first dose of study drug. Note: Subjects with borderline serum pregnancy tests at Screening must have a serum pregnancy test = 3 days later to document continued lack of positive result.
• Must not be using IV or IM corticosteroids greater than or equal to a 40 mg prednisone-equivalent bolus within 30 days of planned randomization
• Must not have active lupus nephritis (progressive Class IV or >1g/day equivalent [1 mg/mg] proteinuria) or have undergone induction therapy within the last 6 months.
• Must not have active neuropsychiatric SLE as defined by the CNS portion of SLEDAI-2K (excluding lupus headache).
Subjects must be naïve or have discontinued, if not currently benefiting from, the following prior to the first dose of study drug per the applicable washout period below or should be at least 5 times the mean terminal elimination half-life of a drug:
· =6 months for Plasmapheresis
· =3 months for Benlysta
· =1 year for rituximab OR = 6 months if B cells have returned to = 50 B cells per microliter
· =3 months for cyclophosphamide
· =4 weeks for abatacept, any anti-TNF therapy, and all other biologics
• Must not have positive titers for all 3 antiphospholipid antibodies known to be associated with venous thrombotic events at Screening: lupus anticoagulant, anti-beta 2 glycoprotein 1, and anticardiolipin antibody.
Must not have confirmed COVID-19: the Baseline visit must be at least
14 days from onset of signs/symptoms or positive SARS-CoV-2 test;
symptomatic subjects must have recovered, defined as resolution of
fever without use of antipyretics and improvement in symptoms.
• Must not have suspected COVID-19: subjects with signs/symptoms
suggestive of COVID-19, known exposure, or high-risk behavior should
undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection
or must be asymptomatic for 14 days from a potential exposure.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Immune system processes [G12]

Systemic Lupus Erythematosus (SLE)
MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Elsubrutinib
Product Code: ABBV-105
Pharmaceutical Form: Capsule
INN or Proposed INN: ELSUBRUTINIB
CAS Number: 1643570-24-4
Current Sponsor code: ABBV-105
Other descriptive name: ABBV-105
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: UPADACITINIB
CAS Number: 2050057-56-0
Current Sponsor code: ABT-494
Other descriptive name: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: UPADACITINIB
CAS Number: 2050057-56-0
Current Sponsor code: ABT-494
Other descriptive name: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Achievement of Responder Index (SRI)-4 and steroid dose = 10 mg prednisone equivalent QD. SLE Responder Index (SRI)-4 is defined as = 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score without worsening of the overall condition (no worsening in Physician's Global Assessment [PhGA], < 0.3 point increase) or the development of significant disease activity in new organ systems (no new British Isles Lupus Assessment Group ([BILAG]) A or > 1 new BILAG B).

Main Objective: The main objective of this study is to evaluate the safety and efficacy of elsubrutinib, upadacitinib and ABBV-599 (elsubrutinib/upadacitinib) combination vs placebo for the treatment of signs and symptoms of Systemic Lupus Erythematosus (SLE) at 24 and 48 weeks in subjects with moderately to severely active SLE and to define optimal dose(s) for further development.

Timepoint(s) of evaluation of this end point: Week 24.

Secondary Objective: Not applicable.

Secondary Outcome(s)

Secondary end point(s): 1. Achievement of SRI-4 at Week 24
2. Achievement of BILAG-Based Combined Lupus Assessment (BICLA)
response at Week 24
3. Achievement of Lupus Low Disease Activity State (LLDAS) at Week 24
4. Steroid burden, assessed as change from Baseline at Week 24
5. Number of mild, moderate, or severe flares per patient-year
(respectively and overall) by Safety of Estrogens in Lupus
Erythematosus National Assessment (SELENA) SLEDAI Flare Index (SFI),
assessed by number and types of flare per subject across treatment
arms through Week 24

Timepoint(s) of evaluation of this end point: Week 24

Secondary ID(s)

2019-000638-20-DE

M19-130

Source(s) of Monetary Support

AbbVie Inc

Ethics review

Status: Approved
Approval date: 12/10/2020
Contact: