Program to Assess Adverse Events and Change in Disease Activity of Oral Upadacitinib in Adult Participants With Moderate to Severe Systemic Lupus Erythematosus

Study Purpose

Systemic Lupus Erythematosus (SLE) is an immune-mediated disease associated with inflammation of multiple organ systems. This study will assess how safe and effective upadacitinib is in treating adult participants with moderately to severely active SLE. Adverse events and change in the disease activity will be assessed. Upadacitinib is an approved drug for rheumatoid arthritis, psoriatic arthritis, and axial spondylarthritis and is being developed for the treatment of SLE. This study is "double-blinded", which means that neither the trial participants nor the study doctors will know who will be given upadacitinib and who will be given placebo (does not contain treatment drug) . This study comprised of 4 sub studies. In Study 1 and Study 2, study doctors put the participants in 1 of the 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Eligible participants from Study 1 and Study 2 will enter Study 3 at week 52 to receive specific doses of upadacitinib. Study 4 is a 104-week continued extension if participation is likely to provide a benefit to their SLE. Approximately 500 participants diagnosed with SLE will be enrolled in each of the Study 1 and Study 2 in approximately 320 sites across the world. Participants will receive oral tablets of upadacitinib or matching placebo once daily for 52 weeks in Study 1 and Study 2. Eligible participants from Study 1 and Study 2 will receive oral tablets of upadacitinib once daily for 52 weeks in Study 3. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 63 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Clinical diagnosis of systemic lupus erythematosus (SLE) at least 24 weeks prior to screening as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/ American College of Rheumatology (ACR) classification criteria for SLE.

- At Screening, must have at least one of the following: - antinuclear antibody (ANA) positive (titer >= 1:80) - anti-double stranded deoxyribonucleic acid (dsDNA) positive.

- anti-Smith positive.

- Hybrid systemic lupus erythematosus disease activity index (hSLEDAI) >= 6, of which >= 4 points are clinical (not based on laboratory criteria), independently reviewed by the MCDR at Screening.

Clinical hSLEDAI score (not based on laboratory criteria) must be re-confirmed as >= 4 at the Baseline visit. Lupus headache or organic brain syndrome do not count towards the hSLEDAI points required for eligibility but should be documented on the hSLEDAI if present.

- Physician's Global Assessment (PhGA) >= 1 during screening period.

- On stable background treatment for >= 60 days prior to Baseline (with the exception of oral corticosteroid [OCS], which must be at a stable dose for >=14 days prior to Baseline) with.

- antimalarial(s) [hydroxychloroquine <= 400 mg daily, chloroquine <= 500 mg daily, quinacrine <= 100 mg daily]; - and/or prednisone (or prednisone-equivalent) (<= 20 mg daily); - and/or no more than 1 of the following: azathioprine (<= 150 mg daily), 6-mercaptopurine (<= 150 mg daily), mycophenolate mofetil (<= 2 g daily), mycophenolate sodium <= 1,440 mg/day, leflunomide (<= 20 mg daily), cyclosporine, tacrolimus, voclosporin (<= 23.7 mg twice daily), methotrexate (<= 25 mg weekly), or mizoribine (<= 150 mg daily).

Exclusion Criteria:

- Class III/IV lupus nephritis that was treated with induction therapy within the 6 months prior to Screening.

- Active neuropsychiatric SLE (excluding lupus headache) within the 6 months prior to Screening.

- SLE overlap syndromes including, but not limited to, rheumatoid arthritis, systemic sclerosis, polymyositis, dermatomyositis, or mixed connective tissue disease (Sjögren's syndrome is permitted).

- Antiphospholipid syndrome and prior unprovoked venous or arterial thrombosis who are not on stable and adequate anticoagulation.

- Two or more episodes of herpes zoster, or one or more episodes of disseminated herpes zoster or herpes zoster ophthalmicus.

- History of malignancy, except for successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix.

- Pregnancy, breastfeeding, or considering becoming pregnant during the study.

- Clinically relevant or significant ECG abnormalities at Screening.

- Planned elective surgery that would impact study procedures or assessments through the completion of the Week 52 assessments.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05843643
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	AbbVie
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	ABBVIE INC.
Principal Investigator Affiliation	AbbVie
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Estonia, France, Germany, Greece, Guatemala, Hungary, Israel, Italy, Japan, Latvia, Lithuania, Mexico, New Zealand, Poland, Portugal, Puerto Rico, Romania, Serbia, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Systemic Lupus Erythematosus
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: Study 1- Upadacitinib Dose A

Participants will receive upadacitinib dose A once daily for 52 weeks.

Placebo Comparator: Study 1- Placebo

Participants will receive upadacitinib matching placebo once daily for 52 weeks.

Experimental: Study 2- Upadacitinib Dose A

Participants will receive upadacitinib dose A once daily for 52 weeks.

Placebo Comparator: Study 2- Placebo

Participants will receive upadacitinib matching placebo once daily for 52 weeks.

Experimental: Study 3- Low Disease Activity Upadacitinib (LDA) Dose A

Participants in the upadacitinib arms from Study 1 or Study 2 with LDA will receive upadacitinib dose A once daily for 52 weeks.

Experimental: Study 3- Low Disease Activity Upadacitinib Dose B

Participants in the upadacitinib arms from Study 1 or Study 2 with LDA will receive upadacitinib dose B once daily for 52 weeks.

Experimental: Study 3- No LDA Upadacitinib Dose A

Participants in the upadacitinib arms from Study 1 or Study 2 with no LDA will receive upadacitinib dose A once daily for 52 weeks.

Experimental: Study 3- Upadacitininb Dose A

Participants in the placebo arms of Study 1 or Study 2 will receive upadacitinib Dose A once daily for 52 weeks.

Experimental: Study 3- Open Label Upadacitinib Dose A

Participants who experience a suspected systemic lupus erythematosus (SLE) flare may receive open label upadacitinib Dose A once daily for the remainder of the study.

Experimental: Study 3- Open Label Upadacitinib Dose B

Participants who reach >= 65 years of age and are still on study drug may receive open-label upadacitinib Dose B once daily, and participants who experience a suspected SLE flare while on upadacitinib Dose B may receive upadacitinib Dose A for the remainder of the study.

Experimental: Study 4- Upadacitinib Dose A

Participants receiving upadacitinib Dose A in Study 3 will continue on this dose once daily for 104 weeks.

Experimental: Study 4- Upadacitinib Dose B

Participants receiving upadacitinib Dose B in Study 3 will continue on this dose once daily for 104 weeks.

Interventions

Drug: - Upadacitinib

Oral Tablets

Drug: - Placebo

Oral Tablet

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Chandler 5289282, Arizona 5551752

Status

Recruiting

Address

AZ Arthritis and Rheumatology /ID# 261848

Chandler 5289282, Arizona 5551752, 85225-2906

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