Upadacitinib for Lupus

(SELECT-SLE Trial)

Recruiting at 429 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Antimalarials, Corticosteroids, Immunosuppressants

Disqualifiers: Lupus nephritis, Neuropsychiatric SLE, Overlap syndromes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

1000 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial does not require you to stop your current medications. You must be on a stable dose of your existing lupus treatments for at least 60 days before starting the trial, except for oral corticosteroids, which need to be stable for at least 14 days.

What makes the drug Upadacitinib unique for treating lupus?

Upadacitinib is unique for treating lupus because it is a Janus kinase (JAK) inhibitor, which works by blocking specific pathways involved in the immune response, potentially offering a new mechanism of action compared to traditional treatments like corticosteroids and immunosuppressants. ^{1 2 3 4 5}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

Adults with moderate to severe Systemic Lupus Erythematosus (SLE) can join this trial. They must have been diagnosed at least 24 weeks ago, meet specific disease criteria including positive ANA and anti-dsDNA tests, and have a certain level of disease activity. Participants should be on stable SLE medication for some time before the study starts.

Inclusion Criteria

I was diagnosed with lupus more than 24 weeks ago.

My lupus is active with a score of 6 or more, mainly from symptoms, not lab tests.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral tablets of upadacitinib or matching placebo once daily for 52 weeks in Study 1 and Study 2

52 weeks

Regular visits at a hospital or clinic

Extension

Eligible participants from Study 1 and Study 2 will receive oral tablets of upadacitinib once daily for 52 weeks in Study 3

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Upadacitinib

Trial Overview The trial is testing Upadacitinib's safety and effectiveness in treating SLE compared to a placebo. It's double-blinded, meaning no one knows who gets the real drug or placebo. The study has three parts: two main studies where participants are randomly assigned treatment or placebo for 52 weeks, followed by a third study based on their initial results.

Participant Groups

Group I: Study 4- Upadacitinib Dose B Experimental Treatment 1 Intervention

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

Group II: Study 4- Upadacitinib Dose A Experimental Treatment 1 Intervention

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

Group III: Study 3- Upadacitininb Dose A Experimental Treatment 1 Intervention

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

Group IV: Study 3- Open Label Upadacitinib Dose B Experimental Treatment 1 Intervention

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.

Group V: Study 3- Open Label Upadacitinib Dose A Experimental Treatment 1 Intervention

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.

Group VI: Study 3- No LDA Upadacitinib Dose A Experimental Treatment 1 Intervention

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

Group VII: Study 3- Low Disease Activity Upadacitinib Dose B Experimental Treatment 1 Intervention

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

Group VIII: Study 3- Low Disease Activity Upadacitinib (LDA) Dose A Experimental Treatment 1 Intervention

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

Group IX: Study 2- Upadacitinib Dose A Experimental Treatment 1 Intervention

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

Group X: Study 1- Upadacitinib Dose A Experimental Treatment 1 Intervention

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

Group XI: Study 1- Placebo Placebo Group 1 Intervention

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

Group XII: Study 2- Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In a Phase IIb trial involving 305 patients with systemic lupus erythematosus (SLE), anifrolumab treatment led to a higher rate of achieving the Lupus Low Disease Activity State (LLDAS) compared to placebo, indicating its efficacy in managing SLE symptoms.

The study found that anifrolumab-treated patients not only reached LLDAS earlier but also spent more time in this state, supporting the use of LLDAS as a meaningful endpoint in SLE clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab. Morand, EF., Trasieva, T., Berglind, A., et al.[2019]

Current lupus treatment trials face significant challenges, including large trial sizes, competition for patients, and complex outcome measures, which can lead to results that are difficult to interpret.

The authors propose new trial designs and strategies based on consultations with experts to enhance the likelihood of successful and interpretable lupus treatment development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus community panel proposals for optimising clinical trials: 2018. Merrill, JT., Manzi, S., Aranow, C., et al.[2022]

An algorithm was developed to predict high disease activity status (HDAS) in lupus patients using simple demographic and laboratory data, achieving an accuracy of 88.6% based on a study of 286 patients over a median of 5.1 years.

The final model outperformed the naïve Bayes classifier, indicating that it can effectively identify patients needing treatment escalation or trial enrollment without relying on the SLEDAI score.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Algorithm for calculating high disease activity in SLE. Hoi, A., Nim, HT., Koelmeyer, R., et al.[2021]

Biologic therapies for systemic lupus erythematosus (SLE) are essential for patients who do not respond to standard treatments, with pharmacokinetic profiles varying significantly based on the type of biologic, including half-lives from 1 week to 1 month.

The review highlights the potential for developing precision dosing strategies using pharmacokinetic-pharmacodynamic models that incorporate SLE biomarkers, which could enhance treatment efficacy and minimize adverse effects by tailoring dosages to individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of Biologic Therapeutics for Treatment of Systemic Lupus Erythematosus. Yu, T., Enioutina, EY., Brunner, HI., et al.[2018]

In a phase III trial with 819 patients, belimumab at 10 mg/kg significantly improved the SLE Responder Index response rate at week 52 compared to placebo (43.2% vs. 33.5%), indicating its efficacy in reducing disease activity in systemic lupus erythematosus (SLE).

Belimumab was generally well tolerated, with serious adverse events being comparable across treatment groups, suggesting that it is a safe addition to standard therapy for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Furie, R., Petri, M., Zamani, O., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Lupus community panel proposals for optimising clinical trials: 2018. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Algorithm for calculating high disease activity in SLE. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of Biologic Therapeutics for Treatment of Systemic Lupus Erythematosus. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. [2022]