A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA)

• ClinicalTrials.gov Identifier: NCT03725202
• Recruitment Status: Recruiting
• First Posted: October 30, 2018
• Last Update Posted: January 13, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: October 27, 2018
• First Posted Date: October 30, 2018
• Last Update Posted Date: January 13, 2021
• Actual Study Start Date: January 24, 2019
• Estimated Primary Completion Date: October 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2018)

Percentage of Participants Achieving Sustained Remission [ Time Frame: At Week 52 ]

Sustained remission is defined as having achieved absence of GCA signs and symptoms from Week 12 through Week 52, and adherence to the protocol-defined CS taper regimen.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 11, 2021)

• Percentage of Participants Achieving Sustained Complete Remission [ Time Frame: Week 12 through Week 52 ]
  Sustained complete remission is defined as having absence of GCA signs and symptoms; normalization of ESR; Normalization of high sensitivity C-reactive protein (hs-CRP) and adherence to the protocol-defined CS taper regimen.
• Cumulative Corticosteroid (CS) exposure [ Time Frame: Up to Week 52 ]
  The cumulative exposure to corticosteroid(s) is assessed.
• Time to First Disease Flare [ Time Frame: Up to Week 52 ]
  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.
• Percentage of Participants Who Experience at Least 1 Disease Flare [ Time Frame: Up to Week 52 ]
  The percentage of participants who experience at least 1 disease flare is assessed
• Percentage of Participants in Complete Remission [ Time Frame: Up to Week 52 ]
  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.
• Change from Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Score (PCS) [ Time Frame: At Week 52 ]
  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.
• Number of Disease Flares per Participant During Period 1 [ Time Frame: Up to Week 52 ]
  The number of disease flares per participant during Period 1 will be assessed.
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: From Week 0 to Week 52 ]
  The FACIT-F 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-F 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.
• Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale [ Time Frame: At Week 52 ]
  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.
• Rate of CS-related Adverse Events [ Time Frame: At Week 52 ]
  The rate of CS-related adverse events will be assessed.

Original Secondary Outcome Measures (submitted: October 27, 2018)

• Percentage of Participants Achieving Sustained Complete Remission [ Time Frame: Week 12 through Week 52 ]
  Sustained complete remission is defined as having absence of GCA signs and symptoms; normalization of ESR; Normalization of CRP and adherence to the protocol-defined CS taper regimen.
• Cumulative CS exposure [ Time Frame: Up to Week 52 ]
  The cumulative exposure to corticosteroid(s) is assessed.
• Time to disease flare [ Time Frame: Up to Week 52 ]
  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.
• Percentage of Participants Who Experience at Least 1 Disease Flare [ Time Frame: Up to Week 52 ]
  The percentage of participants who experience at least 1 disease flare is assessed
• Percentage of Participants in Complete Remission [ Time Frame: Up to Week 52 ]
  Complete remission is defined as having achieved absence of GCA signs and symptoms; normalization of ESR; normalization of CRP and adherence to the protocol-defined CS taper regimen.
• Change from Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) [ Time Frame: At Week 52 ]
  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.
• Number of Disease Flares per Participant During Period 1 [ Time Frame: Up to Week 52 ]
  The number of disease flares per participant during Period 1 will be assessed.
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: From Week 0 to Week 52 ]
  The FACIT-F 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-F 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.
• Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) [ Time Frame: At Week 52 ]
  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.
• Rate of CS-related Adverse Events [ Time Frame: At Week 52 ]
  The rate of CS-related adverse events will be assessed.

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

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis: SELECT-GCA
• Brief Summary: 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 remission in Period 1.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Giant Cell Arteritis (GCA)

Intervention

• Drug: Upadacitinib
  It will be administered orally.
  Other Names:

  • ABT-494
  • RINVOQ
• Drug: Corticosteroid (CS)
  It will be administered orally.
• Other: Placebo
  It will be administered orally.

Study Arms

• Experimental: Arm A
  Upadacitinib dose A administered daily + 26-week CS taper regimen
  Interventions:

  • Drug: Upadacitinib
  • Drug: Corticosteroid (CS)
• Experimental: Arm B
  Upadacitinib dose B administered daily + 26-week CS taper regimen
  Interventions:

  • Drug: Upadacitinib
  • Drug: Corticosteroid (CS)
• Placebo Comparator: Arm C
  Placebo administered daily + 52-week CS taper regimen
  Interventions:

  • Drug: Corticosteroid (CS)
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 27, 2018): 420
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 25, 2024
• Estimated Primary Completion Date: October 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 6 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, HIV, active Tuberculosis, active or chronic recurring infection, active hepatitis B or C.
• Female who is pregnant, breastfeeding, or considering pregnancy during the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, New Zealand, Norway, Portugal, Romania, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT03725202
• Other Study ID Numbers: M16-852; 2017-003978-13 ( EudraCT Number )
• 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.: No

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 and 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: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• 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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Responsible Party: AbbVie
• Study Sponsor: AbbVie
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: January 2021