Upadacitinib for Lupus

(SELECT-SLE Trial)

Recruiting at 512 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of upadacitinib, a medication approved for other inflammatory conditions, in treating systemic lupus erythematosus (SLE), a disease where the immune system attacks various organs. Participants will receive either upadacitinib or a placebo (a non-active substance) to assess its impact on SLE symptoms over time. Those diagnosed with SLE for at least 24 weeks and experiencing moderate to severe symptoms may be eligible. The study requires regular clinic or hospital visits to monitor treatment effects and side effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements for SLE.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that upadacitinib has been safely used in people with conditions like rheumatoid arthritis. This medicine underwent study for other uses before consideration for lupus. Although not yet approved for lupus, studies have found it to be well-tolerated in patients with these other conditions.

In some studies, people taking upadacitinib experienced mild side effects, such as headaches or stomach issues, but these were not serious. The advanced stage of this trial indicates some confidence in the drug's safety for further testing. However, like any medication, there is always a chance of side effects or reactions. Participants should discuss any concerns with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for lupus, like corticosteroids and immunosuppressants, aim to reduce inflammation and suppress the immune system. However, Upadacitinib works differently by targeting the JAK1 pathway, an important component in the inflammatory process. This selective inhibition could lead to more precise control of lupus symptoms with potentially fewer side effects. Researchers are excited because Upadacitinib offers a novel approach that might improve symptom management and quality of life for lupus patients compared to current therapies.

What evidence suggests that this trial's treatments could be effective for SLE?

Studies have shown that upadacitinib can help reduce symptoms in people with systemic lupus erythematosus (SLE). This trial will administer upadacitinib in various doses to evaluate its effectiveness in managing SLE symptoms. Already approved for treating other inflammatory conditions like rheumatoid arthritis, the medication has shown positive results in earlier research, suggesting it might also be effective for SLE, though it is not yet approved for this specific use. Upadacitinib works by targeting certain parts of the immune system to control inflammation. ^{1 2 4 5 6}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1.

news.abbvie.com

news.abbvie.com/2023-03-23-AbbVie-Advances-Upadacitinib-RINVOQ-R-to-Phase-3-Clinical-Trials-in-Systemic-Lupus-Erythematosus

AbbVie Advances Upadacitinib (RINVOQ) to Phase 3 SLE Trials

The use of upadacitinib in systemic lupus erythematosus is not approved and its safety and efficacy have not been evaluated by regulatory ...

2.

acrjournals.onlinelibrary.wiley.com

acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/art.42926

Efficacy & Safety: Upadacitinib or Elsubrutinib for Lupus

Upadacitinib 30 mg alone or in combination with elsubrutinib (ABBV-599 high dose) demonstrated significant improvements in SLE disease activity ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40829888/

results through 104 weeks in a long-term extension study

Conclusions: In this LTE study, upadacitinib monotherapy and upadacitinib/elsubrutinib combined were well tolerated and continued to demonstrate ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02706847

NCT02706847 | A Study to Compare Upadacitinib (ABT- ...

The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo ...

5.

prnewswire.com

prnewswire.com/news-releases/abbvie-advances-upadacitinib-rinvoq-to-phase-3-clinical-trials-in-systemic-lupus-erythematosus-301779254.html

AbbVie Upadacitinib (RINVOQ) to Phase 3 SLE Trials

The use of upadacitinib in systemic lupus erythematosus is not approved and its safety and efficacy have not been evaluated by regulatory ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12366599/

Efficacy and safety of upadacitinib as monotherapy or ...

In this LTE study, upadacitinib monotherapy and upadacitinib/elsubrutinib combined were well tolerated and continued to demonstrate beneficial ...