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

• ClinicalTrials.gov Identifier: NCT05843643
• Recruitment Status: Recruiting
• First Posted: May 6, 2023
• Last Update Posted: May 6, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: April 25, 2023
• First Posted Date: May 6, 2023
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: July 19, 2023
• Estimated Primary Completion Date: October 2, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2023)

Percentage of Participants Achieving British Isles Lupus Assessment Group Based Combined Lupus Assessment (BICLA) Response [ Time Frame: At Week 52 ]

BICLA is a composite responder index based on improvement in organ systems without worsening of the overall condition and improvement in disease activity.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 11, 2024)

• Percentage of Flares Participants Experiencing Over Time (Number of Flares Per Patient-Year) [ Time Frame: Week 52 ]
  Flare is defined by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) Systemic lupus erythematosus disease activity index (SLEDAI) Flare Index (SFI). An index defining Systemic lupus erythematosus (SLE) flares using changes in the Hybrid SLEDAI (hSLEDAI) score, definitions of worsening signs and symptoms, treatment changes, and Physician's Global Assessment of Disease Activity. Flare rate is number of flares per patient-year.
• Percentage of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI) -4 [ Time Frame: At Week 52 ]
  SRI is a composite responder index based on improvement in disease activity (number following SRI indicates numerical improvement in hSLEDAI score) without worsening of the overall condition (no worsening in Physician's Global Assessment (PhGA), < 0.3 point increase) or the development of significant disease activity in new organ systems (no new British Isles Lupus Assessment Group [BILAG] A or > 1 new BILAG B).
• Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) [ Time Frame: At Week 52 ]
  LLDAS is a state of low disease activity based on SLEDAI score (hSLEDAI score <= 4 excluding hSLEDAI activity in major organ systems), absence of SLE disease activity in major organ systems and new disease activity, Physician's Global Assessment (PhGA <= 1), and concomitant medication usage.
• Time to First Flare per SELENA SLEDAI Flare Index (SFI) [ Time Frame: Week 52 ]
  SFI is an index defining SLE flares using changes in the hSLEDAI score, definitions of worsening signs and symptoms, treatment changes, and Physician's Global Assessment of Disease Activity.
• Percentage of Participants Achieving Oral Glucocorticoid Dose <=7.5 mg/day Prednisone-Equivalent [ Time Frame: From Week 44 to Week 52 ]
  Achievement of oral glucocorticoid dose <=7.5 mg/day prednisone-equivalent among participants taking >= 10 mg/day prednisone-equivalent at baseline.
• Percentage of Participants Achieving >= 50% Improvement in Tender or Swollen Joints [ Time Frame: Week 52 ]
  Achievement of >= 50% improvement in tender or swollen joints among participants with >= 3 swollen joints and >= 6 total affected joints at Baseline.
• Percentage of Participants Achieving >= 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score [ Time Frame: Week 52 ]
  CLASI index used to assess cutaneous manifestations of SLE summarizing the activity of the disease. Scores range from 0 to 70, with higher scores indicating more severity. Achievement of >= 50% reduction in CLASI activity score among participants with baseline score >=10.
• Change from Baseline in Lupus Pain Numerical Rating Scale (NRS) [ Time Frame: Baseline to Week 52 ]
  The Lupus Pain-NRS is a single-item questionnaire in which participants are asked to rate their overall pain level due to lupus over the last week. The Lupus Pain-NRS scores range from 0 to 10, with higher scores indicating a higher level of pain.
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Version 4 [ Time Frame: Baseline to Week 52 ]
  The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants. Participants respond to the questions on a scale from 0 (not at all) to 4 (very much). The FACIT-Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue score ranges from 0 to 52, where higher scores represent less fatigue.
• Change from Baseline in 36-Item Short Form Health Survey (SF-36) Acute Physical Component Summary (PCS) [ Time Frame: Baseline to Week 52 ]
  The SF-36v2® Health Survey Acute is a general HRQoL instrument with extensive use in multiple disease states. The instrument comprises 36 total items (questions) targeting a participants's functional health and well-being in 8 dimensions (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Scoring is totaled into a Physical Component Summary and a Mental Component Summary. Higher scores indicate a better state of health.

Original Secondary Outcome Measures (submitted: April 25, 2023)

• Percentage of Flares Participants Experiencing Over Time (Number of Flares Per Patient-Year) [ Time Frame: Week 52 ]
  Flare is defined by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) Systemic lupus erythematosus disease activity index (SLEDAI) Flare Index (SFI). An index defining Systemic lupus erythematosus (SLE) flares using changes in the Hybrid SLEDAI (hSLEDAI) score, definitions of worsening signs and symptoms, treatment changes, and Physician's Global Assessment of Disease Activity. Flare rate is number of flares per patient-year.
• Percentage of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI) -4 [ Time Frame: At Week 52 ]
  SRI is a composite responder index based on improvement in disease activity (number following SRI indicates numerical improvement in hSLEDAI score) without worsening of the overall condition (no worsening in Physician's Global Assessment (PhGA), < 0.3 point increase) or the development of significant disease activity in new organ systems (no new British Isles Lupus Assessment Group [BILAG] A or > 1 new BILAG B).
• Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) [ Time Frame: At Week 52 ]
  LLDAS is a state of low disease activity based on SLEDAI score (hSLEDAI score <= 4 excluding hSLEDAI activity in major organ systems), absence of SLE disease activity in major organ systems and new disease activity, Physician's Global Assessment (PhGA <= 1), and concomitant medication usage.
• Time to First Flare per SELENA SLEDAI Flare Index (SFI) [ Time Frame: Week 52 ]
  SFI is an index defining SLE flares using changes in the hSLEDAI score, definitions of worsening signs and symptoms, treatment changes, and Physician's Global Assessment of Disease Activity.
• Percentage of Participants Achieving Glucocorticoid Dose <=7.5 mg/day Prednisone-Equivalent [ Time Frame: From Week 44 to Week 52 ]
  Achievement of glucocorticoid dose <=7.5 mg/day prednisone-equivalent among participants taking >= 10 mg/day prednisone-equivalent at baseline.
• Change from Baseline in Lupus Pain Numerical Rating Scale (NRS) [ Time Frame: Baseline to Week 28 ]
  The Lupus Pain-NRS is a single-item questionnaire in which participants are asked to rate their overall pain level due to lupus over the last week. The Lupus Pain-NRS scores range from 0 to 10, with higher scores indicating a higher level of pain.
• Percentage of Participants Achieving >= 50% Improvement in Tender or Swollen Joints [ Time Frame: Week 52 ]
  Achievement of >= 50% improvement in tender or swollen joints among participants with >= 3 swollen joints and >= 6 total affected joints at Baseline.
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Version 4 [ Time Frame: Baseline to Week 28 ]
  The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants. Participants respond to the questions on a scale from 0 (not at all) to 4 (very much). The FACIT-Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue score ranges from 0 to 52, where higher scores represent less fatigue.
• Change from Baseline in 36-Item Short Form Health Survey (SF-36) Acute Physical Component Summary (PCS) [ Time Frame: Baseline to Week 28 ]
  The SF-36v2® Health Survey Acute is a general HRQoL instrument with extensive use in multiple disease states. The instrument comprises 36 total items (questions) targeting a participants's functional health and well-being in 8 dimensions (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Scoring is totaled into a Physical Component Summary and a Mental Component Summary. Higher scores indicate a better state of health.
• Percentage of Participants Achieving >= 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score [ Time Frame: Week 52 ]
  CLASI index used to assess cutaneous manifestations of SLE summarizing the activity of the disease. Scores range from 0 to 70, with higher scores indicating more severity. Achievement of >= 50% reduction in CLASI activity score among participants with baseline score >=10.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Program to Assess Adverse Events and Change in Disease Activity of Oral Upadacitinib in Adult Participants With Moderate to Severe Systemic Lupus Erythematosus
• Official Title: SELECT-SLE: A Phase 3 Program to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Moderately to Severely Active SLE

Brief Summary

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 3 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 based on their disease activity and their original treatment assignment in Study 1 or 2. 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Drug: Upadacitinib
  Oral Tablets
  Other Name: RINVOQ
• Drug: Placebo
  Oral Tablet

Study Arms

• Experimental: Study 1- Upadacitinib Dose A
  Participants will receive upadacitinib dose A once daily for 52 weeks.
  Intervention: Drug: Upadacitinib
• Placebo Comparator: Study 1- Placebo
  Participants will receive upadacitinib matching placebo once daily for 52 weeks.
  Intervention: Drug: Placebo
• Experimental: Study 2- Upadacitinib Dose A
  Participants will receive upadacitinib dose A once daily for 52 weeks.
  Intervention: Drug: Upadacitinib
• Placebo Comparator: Study 2- Placebo
  Participants will receive upadacitinib matching placebo once daily for 52 weeks.
  Intervention: Drug: Placebo
• 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.
  Intervention: Drug: Upadacitinib
• 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.
  Intervention: Drug: Upadacitinib
• 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.
  Intervention: Drug: Upadacitinib
• 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.
  Intervention: Drug: Upadacitinib
• 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.
  Intervention: Drug: Upadacitinib
• 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.
  Intervention: Drug: Upadacitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 25, 2023): 1000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2027
• Estimated Primary Completion Date: October 2, 2026 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 63 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Bosnia and Herzegovina, Brazil, Bulgaria, China, Colombia, Croatia, Estonia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, New Zealand, Poland, Portugal, Puerto Rico, Romania, Serbia, Slovakia, South Africa, Spain, Switzerland, Taiwan, United Kingdom, United States
• Removed Location Countries: Argentina, Belgium, Chile, Mexico, Turkey

Administrative Information

• NCT Number: NCT05843643
• Other Study ID Numbers: M23-699; 2023-503655-10-00 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: May 2024