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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Systemic Lupus Erythematosus (SLE)

Intervention / Treatment
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* Drug: Elsubrutinib
* Drug: Placebo for Elsubrutinib
* Drug: Upadacitinib
* Drug: Placebo for Upadacitinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, ABBV-599, ABBV-105, ABT-494, Elsubrutinib, Upadacitinib