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

Phase 3Active Not RecruitingNCT05843643

AbbVie1,014 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 63 Years

Medical Language ↔ Plain English

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.

Locations (369)

AZ Arthritis and Rheumatology /ID# 261848

Chandler, Arizona, United States

AZ Arthritis and Rheumotology Research, PLLC - Flagstaff /ID# 254767

Flagstaff, Arizona, United States

Arizona Arthritis & Rheumatology Research, PLLC /ID# 252820

Gilbert, Arizona, United States

Arizona Arthritis and Rheumatology Research - Glendale Office /ID# 252824

Glendale, Arizona, United States

Arizona Arthritis & Rheumatology Research, PLLC /ID# 261845

Mesa, Arizona, United States

Outcomes

Primary Outcomes

Percentage of Participants Achieving British Isles Lupus Assessment Group Based Combined Lupus Assessment (BICLA) Response

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

Time frame: At Week 52

Secondary Outcomes

Percentage of Flares Participants Experiencing Over Time.

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.

Time frame: Week 52

Percentage of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI) -4

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).

Time frame: At Week 52

Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS)

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 frame: At Week 52

Time to First Flare per SELENA SLEDAI Flare Index (SFI)

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.

Time frame: Week 52

Percentage of Participants Achieving Oral Glucocorticoid Dose <=7.5 mg/day Prednisone-Equivalent

Achievement of oral glucocorticoid dose \<=7.5 mg/day prednisone-equivalent among participants taking \>= 10 mg/day prednisone-equivalent at baseline.

Time frame: From Week 44 to Week 52

Percentage of Participants Achieving >= 50% Improvement in Tender or Swollen Joints

Achievement of \>= 50% improvement in tender or swollen joints among participants with \>= 3 swollen joints and \>= 6 total affected joints at Baseline.

Time frame: Week 52

Percentage of Participants Achieving >= 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score

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.

Time frame: Week 52

Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Version 4

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.

Time frame: Baseline to Week 52

Change from Baseline in Lupus Pain Numerical Rating Scale (NRS)

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.

Time frame: At Week 52

Change from Baseline in 36-Item Short Form Health Survey (SF-36) Acute Physical Component Summary (PCS)

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.

Time frame: Baseline to Week 52

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

Overview

Conditions

Interventions

Eligibility

Locations (369)

Outcomes

Primary Outcomes

Secondary Outcomes