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) (SLEek)

AbbVie

Status and phase: Completed; Phase 2

Conditions: Systemic Lupus Erythematosus (SLE)

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03978520

2019-000638-20 (EudraCT Number)

M19-130

Details and patient eligibility

About

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.

Enrollment: 341 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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341 participants in 5 patient groups, including a placebo group

Elsubrutinib placebo/upadacitinib placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo for elsubrutinib

Drug: Placebo for upadacitinib

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

Experimental group

Description:

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

Treatment:

Drug: Upadacitinib

Drug: Elsubrutinib

Elsubrutinib placebo/upadacitinib 30 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo for elsubrutinib

Drug: Upadacitinib

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

Experimental group

Description:

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

Treatment:

Drug: Upadacitinib

Drug: Elsubrutinib

Elsubrutinib 60 mg/upadacitinib placebo

Experimental group

Description:

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:

Drug: Placebo for upadacitinib

Drug: Elsubrutinib