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

AbbVie

Status and phase: Completed; Phase 2

Conditions: Systemic Lupus Erythematosus (SLE)

Treatments: Drug: Elsubrutinib; Drug: Placebo for Upadacitinib; Drug: Placebo for Elsubrutinib; Drug: Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04451772

M20-186

2020-001690-72 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 185 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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185 participants in 6 patient groups

ABBV-599 High Dose (Elsubrutinib 60 mg/upadacitinib 30 mg) -> ABBV-599 High Dose

Experimental group

Description:

Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.

Treatment:

Drug: Upadacitinib

Drug: Elsubrutinib

Elsubrutinib placebo/upadacitinib 30 mg -> Elsubrutinib placebo/upadacitinib 30 mg

Experimental group

Description:

Participants received placebo capsules for elsubrutinib once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.

Treatment:

Drug: Upadacitinib

Drug: Placebo for Elsubrutinib

Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 High Dose

Experimental group

Description:

Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day in the current study (M20-186) for up to 56 weeks.

Treatment:

Drug: Upadacitinib

Drug: Elsubrutinib

ABBV-599 Low Dose (Elsubrutinib 60 mg/upadacitinib 15 mg) -> ABBV-599 Low Dose

Experimental group

Description:

Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.

Treatment:

Drug: Upadacitinib

Drug: Elsubrutinib

Elsubrutinib 60 mg/upadacitinib placebo -> Elsubrutinib 60 mg/upadacitinib placebo

Experimental group

Description:

Participants received elsubrutinib 60 mg capsules once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks.

Treatment:

Drug: Placebo for Upadacitinib

Drug: Elsubrutinib

Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 Low Dose

Experimental group

Description:

Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in the current study (M20-186) for up to 56 weeks.

Treatment:

Drug: Upadacitinib

Drug: Elsubrutinib