A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis

Study Overview
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Brief Summary
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This study consists of two periods. The objective of Period 1 is to evaluate the efficacy of upadacitinib in combination with a 26-week corticosteroid (CS) taper regimen compared to placebo in combination with a 52-week CS taper regimen, as measured by the proportion of participants in sustained remission at Week 52, and to assess the safety and tolerability of upadacitinib in participants with giant cell arteritis (GCA). The objective of period 2 is to evaluate the safety and efficacy of continuing versus withdrawing upadacitinib in maintaining remission in participants who achieved sustained remission in Period 1.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis: SELECT-GCA

Conditions
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Giant Cell Arteritis (GCA)

Intervention / Treatment
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* Drug: Upadacitinib
* Drug: Corticosteroid (CS)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of giant cell arteritis (GCA) according to the following criteria: History of erythrocyte sedimentation rate (ESR) >= 50 mm/hour or high sensitivity C-reactive protein (hsCRP)/CRP >=1.0 mg/dL Presence of at least one of the following: Unequivocal cranial symptoms of GCA or Unequivocal symptoms of polymyalgia rheumatica (PMR) Presence of at least one of the following: temporal artery biopsy revealing features of GCA or evidence of large vessel vasculitis by angiography or cross-sectional imaging such as ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET). Active GCA, either new onset or relapsing, within 8 weeks of Baseline. Participants must have received treatment with >=40 mg prednisone (or equivalent) at any time prior to Baseline and be receiving prednisone (or equivalent) >= 20 mg once daily (QD) at Baseline. Participants must have GCA that, in the opinion of the investigator, is clinically stable to allow the participant to safely initiate the protocol-defined corticosteroid (CS) taper regimen. Females must either be postmenopausal or permanently surgically sterile or, practicing at least 1 specified method of birth control through the study. Exclusion Criteria: Prior exposure to any Janus Kinase (JAK) inhibitor. Treatment with an interleukin-6 (IL-6) inhibitor within 4 weeks of study start, or prior treatment with an IL-6 inhibitor and experienced a disease flare during treatment. Use of any of the following systemic immunosuppressant treatments within the specified timeframe prior to study start: Anakinra within 1 week of study start. Methotrexate, hydroxychloroquine, cyclosporine, azathioprine, or mycophenolate within 4 weeks of study start. Oral corticosteroid (CS) for conditions other than GCA within 4 week of study start, or intravenous CS within 4 weeks of study start. Greater than or equal to 8 weeks for leflunomide if no elimination procedure was followed, or adhere to an elimination procedure. Cell-depleting agents or alkylating agents including cyclophosphamide within 6 months of study start. Current or past history of infection including herpes zoster or herpes simplex, human immunodeficiency virus (HIV), active Tuberculosis, active or chronic recurring infection, active hepatitis B or C. Female who is pregnant, breastfeeding, or considering pregnancy during the study.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Upadacitinib dose A administered daily + 26-week CS taper regimen | Drug: Upadacitinib<br>* It will be administered orally.<br>* Other names: RINVOQ;Drug: Corticosteroid (CS)<br>* It will be administered orally.<br>|
| Experimental: Arm B<br>Upadacitinib dose B administered daily + 26-week CS taper regimen | Drug: Upadacitinib<br>* It will be administered orally.<br>* Other names: RINVOQ;Drug: Corticosteroid (CS)<br>* It will be administered orally.<br>|
| Placebo Comparator: Arm C<br>Placebo administered daily + 52-week CS taper regimen | Drug: Corticosteroid (CS)<br>* It will be administered orally.<br>Other: Placebo<br>* It will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Remission | Sustained remission is defined as having achieved absence of giant cell arteritis (GCA) signs and symptoms from Week 12 through Week 52, and adherence to the protocol-defined corticosteroid (CS) taper regimen. | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Complete Remission | Sustained complete remission is defined as having absence of GCA signs and symptoms; normalization of erythrocyte sedimentation rate (ESR); Normalization of high sensitivity C-reactive protein (hs-CRP) and adherence to the protocol-defined CS taper regimen. | Week 12 through Week 52 | 
| Cumulative Corticosteroid (CS) exposure | The cumulative exposure to corticosteroid(s) is assessed. | Up to Week 52 | 
| Time to First Disease Flare | Disease flare is defined as an event determined by the investigator to represent recurrence of GCA signs or symptoms or an ESR measurement > 30 mm/hr (attributable to GCA) AND requiring an increase in CS dose. | Up to Week 52 | 
| Percentage of Participants Who Experience at Least 1 Disease Flare | The percentage of participants who experience at least 1 disease flare is assessed | Up to Week 52 | 
| Percentage of Participants in Complete Remission | Complete remission is defined as having achieved absence of GCA signs and symptoms; normalization of ESR; normalization of hs-CRP and adherence to the protocol-defined CS taper regimen. | Up to Week 52 | 
| Change from Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Score (PCS) | The SF-36 is a generic health-related quality-of-life instrument that can be used across age, disease and treatment groups and includes 8 domains: physical functioning, role limitations due to physical health problems, role limitations due to emotional health problems, social functioning, pain, energy/fatigue, emotional well-being, and general health problems. | At Week 52 | 
| Number of Disease Flares per Participant | The number of disease flares per participant during Period 1 will be assessed. | Up to Week 52 | 
| Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) | The FACIT-Fatigue is a 13-item electronic-patient reported outcome (ePRO) measure of fatigue, which has been validated in the general population and in other chronic diseases. The FACIT-Fatigue content and measurement validity and related reliability has been extensively tested in the psoriatic arthritis (PsA) population, with evidence of reliability, construct validity, and responsiveness. | From Week 0 to Week 52 | 
| Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale | The Treatment Satisfaction Questionnaire for Medications (TSQM) is a generic ePRO measure of treatment satisfaction, developed to compare treatment satisfaction between medication types and conditions. TSQM comprises of 14 items to assess 4 domains (effectiveness, side effects, convenience, and global satisfaction). The TSQM items are rated on a Likert scale (1 = extremely dissatisfied to 7 = extremely satisfied). Scores for each of the 4 domains range from 0 to 100, with higher scores corresponding to higher satisfaction. | At Week 52 | 
| Rate of CS-related Adverse Events | The rate of CS-related adverse events will be assessed. | At Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Giant Cell Arteritis (GCA), ABT-494, Upadacitinib