Giant Cell Arteritis (GCA)
Conditions
Keywords
Giant Cell Arteritis (GCA), ABT-494, Upadacitinib
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 sustained remission in Period 1.
Interventions
DRUGUpadacitinib
Administered orally once a day
At Baseline, all participants switched to corticosteroids (CS) provided by the sponsor with the oral prednisone or prednisolone dose at 20, 30, 40, 50, or 60 mg QD. The initial dose of prednisone or prednisolone was at the discretion of the investigator, based on disease severity and comorbid medical conditions, at a minimum of 20 mg QD at Baseline. At Baseline, if a participant was on a dose other than 20, 30, 40, 50, or 60 mg QD, the dose was rounded up or down, as clinically indicated per investigator discretion, to the nearest of these doses. Prednisone or prednisolone was tapered according to a predefined schedule over a 26- or 52-week period. Open-label prednisone or prednisolone was provided until the dose was tapered to 20 mg/day. Subsequently, blinded prednisone or prednisolone was provided for the remaining blinded taper regimen through Week 52.
OTHERPlacebo
Administered orally once a day
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Remission at Week 52 | From Week 12 to Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Complete Remission From Week 12 Through Week 52 | Week 12 through Week 52 | Sustained complete remission is defined as having absence of giant cell arteritis (GCA) signs and symptoms from Week 12 through Week 52; normalization of erythrocyte sedimentation rate (ESR); normalization of high sensitivity C-reactive protein (hs-CRP) and adherence to the protocol-defined CS taper regimen. |
| Cumulative Corticosteroid (CS) Exposure Through Week 52 | Baseline up to Week 52 | The cumulative exposure to corticosteroid(s) through Week 52 of the study was documented. |
| Time to First Disease Flare Through Week 52 | Baseline up to Week 52 | Disease flare is defined as an event determined by the investigator to represent recurrence of Giant Cell Arteritis (GCA) signs or symptoms or an erythrocyte sedimentation rate (ESR) measurement \> 30 mm/hr (attributable to GCA) AND requiring an increase in corticosteroid (CS) dose. |
| Percentage of Participants Who Experience at Least 1 Disease Flare Through Week 52 | Baseline up to Week 52 | The percentage of participants who experience at least 1 disease flare was calculated. Disease flare is defined as an event determined by the investigator to represent recurrence of Giant Cell Arteritis (GCA) signs or symptoms or an erythrocyte sedimentation rate (ESR) measurement \> 30 mm/hr (attributable to GCA) AND requiring an increase in corticosteroid (CS) dose. |
| Percentage of Participants in Complete Remission at Week 52 | At Week 52 | Complete remission is defined as having achieved absence of Giant Cell Arteritis (GCA) signs and symptoms; normalization of erythrocyte sedimentation rate (ESR) to \< 30 mm/hr-- if ESR ≥30 mm/hr and elevation is not attributable to GCA, this criterion can still be met); normalization of high sensitivity C-reactive protein (hs-CRP) to \< 1 mg/dL; and adherence to the protocol-defined corticosteroid (CS) taper regimen. |
| Percentage of Participants in Complete Remission at Week 24 | At Week 24 | Complete remission is defined as having achieved absence of Giant Cell Arteritis (GCA) signs and symptoms; normalization of erythrocyte sedimentation rate (ESR) to \< 30 mm/hr-- if ESR ≥30 mm/hr and elevation is not attributable to GCA, this criterion can still be met); normalization of high sensitivity C-reactive protein (hs-CRP) to \< 1 mg/dL; and adherence to the protocol-defined corticosteroid (CS) taper regimen. |
| Change From Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 52 | Baseline, Week 52 | The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary (PCS) is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The SF-36 PCS ranges from 0 to 100. A linear algorithm was applied to the calculation of the PCS which has a normative mean value of 50. Higher scores are associated with less disability; a score of 100 is equivalent to no disability and a score of 0 is equivalent to maximum disability. A positive change from the Baseline score indicates improvement. |
| Number of Disease Flares Per Participant Through Week 52 | Baseline up to Week 52 | The number of disease flares per participant during Period 1 was documented, and was adjusted by the duration of study participation. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) at Week 52 | Baseline, 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 in the previous 7 days, including physical fatigue, functional fatigue, emotional fatigue, and social consequences of fatigue. 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 items worded in the negative direction. The FACIT-Fatigue score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement. |
| Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale at Week 52 | 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. A positive change from Baseline indicates improvement. |
| Rate of Corticosteroid-related Adverse Events Though Week 52 | Baseline up to Week 52 | The rate of corticosteroid-related adverse events was calculated, and was adjusted by duration of study drug exposure. |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Portugal, Romania, Russia, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Participant flow
Recruitment details
This trial was conducted at 100 sites in 23 countries. Participants were randomized via in a 2:1:1 ratio to receive either upadacitinib 15 mg or 7.5 mg once daily in combination with a predefined 26-week CS taper regimen, or placebo with a predefined 52-week CS taper regimen
Pre-assignment details
Those assigned to upadacitinib who achieved sustained remission for at least 24 consecutive weeks prior to Week 52 visit (at the end of Period 1) were re-randomized in a 2:1 ratio to either stay on upadacitinib or switch to placebo in Period 2. Those on placebo who achieved sustained remission for at least 24 weeks prior to Week 52 visit continued on placebo in Period 2.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + 52-week CS Taper Participants received placebo tablets for upadacitinib administered orally once daily (QD) for 52 weeks and a 52-week corticosteroid (CS) taper regimen during Period 1. | 112 |
| 7.5 mg Upadacitinib + 26-week CS Taper Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1. | 107 |
| 15 mg Upadacitinib + 26-week CS Taper Participants received 15 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1. | 209 |
| Total | 428 |
Baseline characteristics
| Characteristic | Placebo + 52-week CS Taper | 7.5 mg Upadacitinib + 26-week CS Taper | 15 mg Upadacitinib + 26-week CS Taper | Total |
|---|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 7.33 | 71.1 years STANDARD_DEVIATION 7.55 | 70.8 years STANDARD_DEVIATION 7.31 | 71.1 years STANDARD_DEVIATION 7.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 107 Participants | 105 Participants | 203 Participants | 415 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 10 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 103 Participants | 99 Participants | 199 Participants | 401 Participants |
| Sex: Female, Male Female | 77 Participants | 80 Participants | 156 Participants | 313 Participants |
| Sex: Female, Male Male | 35 Participants | 27 Participants | 53 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 112 | 0 / 107 | 3 / 210 | 0 / 43 | 0 / 39 | 0 / 14 | 0 / 92 | 0 / 35 |
| other Total, other adverse events | 90 / 112 | 88 / 107 | 174 / 210 | 34 / 43 | 27 / 39 | 12 / 14 | 67 / 92 | 31 / 35 |
| serious Total, serious adverse events | 24 / 112 | 14 / 107 | 50 / 210 | 9 / 43 | 6 / 39 | 1 / 14 | 14 / 92 | 5 / 35 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Remission at Week 52
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.
Time frame: From Week 12 to Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1; non-responder imputation incorporating multiple imputation or non-responder imputation only if there were no missing data due to COVID-19 logistic restrictions was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + 52-week CS Taper | Percentage of Participants Achieving Sustained Remission at Week 52 | 29.0 percentage of participants |
| 7.5 mg Upadacitinib + 26-week CS Taper | Percentage of Participants Achieving Sustained Remission at Week 52 | 41.1 percentage of participants |
| 15 mg Upadacitinib + 26-week CS Taper | Percentage of Participants Achieving Sustained Remission at Week 52 | 46.4 percentage of participants |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.001995% CI: [6.3, 27.8]Cochran-Mantel-Haenszel
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.057995% CI: [-0.4, 24.6]Cochran-Mantel-Haenszel
Secondary
Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale 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. A positive change from Baseline indicates improvement.
Time frame: At Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1 with both Baseline and post-Baseline visit values
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo + 52-week CS Taper | Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale at Week 52 | 68.8428 units on a scale |
| 7.5 mg Upadacitinib + 26-week CS Taper | Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale at Week 52 | 74.2644 units on a scale |
| 15 mg Upadacitinib + 26-week CS Taper | Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale at Week 52 | 71.5753 units on a scale |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.357395% CI: [-3.102, 8.567]Mixed-Effect Model Repeat Measurement
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.120395% CI: [-1.4269, 12.2701]Mixed-Effect Model Repeat Measurement
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) at 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 in the previous 7 days, including physical fatigue, functional fatigue, emotional fatigue, and social consequences of fatigue. 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 items worded in the negative direction. The FACIT-Fatigue score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement.
Time frame: Baseline, Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1 with both Baseline and post-Baseline visit values
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo + 52-week CS Taper | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) at Week 52 | -2.4 units on a scale |
| 7.5 mg Upadacitinib + 26-week CS Taper | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) at Week 52 | 1.1 units on a scale |
| 15 mg Upadacitinib + 26-week CS Taper | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) at Week 52 | 1.7 units on a scale |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.003695% CI: [1.33, 6.76]Mixed-Effect Model Repeat Measurement
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.033895% CI: [0.27, 6.7]Mixed-Effect Model Repeat Measurement
Secondary
Change From Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 52
The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary (PCS) is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The SF-36 PCS ranges from 0 to 100. A linear algorithm was applied to the calculation of the PCS which has a normative mean value of 50. Higher scores are associated with less disability; a score of 100 is equivalent to no disability and a score of 0 is equivalent to maximum disability. A positive change from the Baseline score indicates improvement.
Time frame: Baseline, Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1 with both Baseline and post-Baseline visit values
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo + 52-week CS Taper | Change From Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 52 | -1.2892 units on a scale |
| 7.5 mg Upadacitinib + 26-week CS Taper | Change From Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 52 | 1.3202 units on a scale |
| 15 mg Upadacitinib + 26-week CS Taper | Change From Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 52 | 2.4634 units on a scale |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.001995% CI: [1.3932, 6.1119]Mixed-Effect Model Repeat Measurement
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.06795% CI: [-0.1841, 5.4028]Mixed-Effect Model Repeat Measurement
Secondary
Cumulative Corticosteroid (CS) Exposure Through Week 52
The cumulative exposure to corticosteroid(s) through Week 52 of the study was documented.
Time frame: Baseline up to Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1. As observed analysis; participants who did not have an evaluation on a scheduled visit were excluded from the analysis for that visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + 52-week CS Taper | Cumulative Corticosteroid (CS) Exposure Through Week 52 | 2882.0 mg |
| 7.5 mg Upadacitinib + 26-week CS Taper | Cumulative Corticosteroid (CS) Exposure Through Week 52 | 1905.0 mg |
| 15 mg Upadacitinib + 26-week CS Taper | Cumulative Corticosteroid (CS) Exposure Through Week 52 | 1615.0 mg |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: <0.0001van Elteren test
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: <0.0001van Elteren test
Secondary
Number of Disease Flares Per Participant Through Week 52
The number of disease flares per participant during Period 1 was documented, and was adjusted by the duration of study participation.
Time frame: Baseline up to Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1; as observed analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + 52-week CS Taper | Number of Disease Flares Per Participant Through Week 52 | 0.7 Disease Flare per Participant per Year |
| 7.5 mg Upadacitinib + 26-week CS Taper | Number of Disease Flares Per Participant Through Week 52 | 0.6 Disease Flare per Participant per Year |
| 15 mg Upadacitinib + 26-week CS Taper | Number of Disease Flares Per Participant Through Week 52 | 0.4 Disease Flare per Participant per Year |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: 0.00195% CI: [0.4, 0.8]Poisson regression model
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.272295% CI: [0.6, 1.2]Poisson regression model
Secondary
Percentage of Participants Achieving Sustained Complete Remission From Week 12 Through Week 52
Sustained complete remission is defined as having absence of giant cell arteritis (GCA) signs and symptoms from Week 12 through Week 52; normalization of erythrocyte sedimentation rate (ESR); normalization of high sensitivity C-reactive protein (hs-CRP) and adherence to the protocol-defined CS taper regimen.
Time frame: Week 12 through Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1; non-responder imputation incorporating multiple imputation or non-responder imputation only if there were no missing data due to COVID-19 logistic restrictions was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + 52-week CS Taper | Percentage of Participants Achieving Sustained Complete Remission From Week 12 Through Week 52 | 16.1 percentage of participants |
| 7.5 mg Upadacitinib + 26-week CS Taper | Percentage of Participants Achieving Sustained Complete Remission From Week 12 Through Week 52 | 26.2 percentage of participants |
| 15 mg Upadacitinib + 26-week CS Taper | Percentage of Participants Achieving Sustained Complete Remission From Week 12 Through Week 52 | 37.1 percentage of participants |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: <0.000195% CI: [11.3, 30.2]Cochran-Mantel-Haenszel
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.069995% CI: [-0.8, 20.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Complete Remission at Week 24
Complete remission is defined as having achieved absence of Giant Cell Arteritis (GCA) signs and symptoms; normalization of erythrocyte sedimentation rate (ESR) to \< 30 mm/hr-- if ESR ≥30 mm/hr and elevation is not attributable to GCA, this criterion can still be met); normalization of high sensitivity C-reactive protein (hs-CRP) to \< 1 mg/dL; and adherence to the protocol-defined corticosteroid (CS) taper regimen.
Time frame: At Week 24
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1; non-responder imputation incorporating multiple imputation or non-responder imputation only if there were no missing data due to COVID-19 logistic restrictions was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + 52-week CS Taper | Percentage of Participants in Complete Remission at Week 24 | 36.1 percentage of participants |
| 7.5 mg Upadacitinib + 26-week CS Taper | Percentage of Participants in Complete Remission at Week 24 | 39.3 percentage of participants |
| 15 mg Upadacitinib + 26-week CS Taper | Percentage of Participants in Complete Remission at Week 24 | 57.2 percentage of participants |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.000295% CI: [9.7, 31.9]Cochran-Mantel-Haenszel
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.627695% CI: [-9.6, 16]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Complete Remission at Week 52
Complete remission is defined as having achieved absence of Giant Cell Arteritis (GCA) signs and symptoms; normalization of erythrocyte sedimentation rate (ESR) to \< 30 mm/hr-- if ESR ≥30 mm/hr and elevation is not attributable to GCA, this criterion can still be met); normalization of high sensitivity C-reactive protein (hs-CRP) to \< 1 mg/dL; and adherence to the protocol-defined corticosteroid (CS) taper regimen.
Time frame: At Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1; non-responder imputation incorporating multiple imputation or non-responder imputation only if there were no missing data due to COVID-19 logistic restrictions was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + 52-week CS Taper | Percentage of Participants in Complete Remission at Week 52 | 19.6 percentage of participants |
| 7.5 mg Upadacitinib + 26-week CS Taper | Percentage of Participants in Complete Remission at Week 52 | 43.0 percentage of participants |
| 15 mg Upadacitinib + 26-week CS Taper | Percentage of Participants in Complete Remission at Week 52 | 50.2 percentage of participants |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: <0.000195% CI: [20.4, 40.2]Cochran-Mantel-Haenszel
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: <0.000195% CI: [11.7, 35.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Experience at Least 1 Disease Flare Through Week 52
The percentage of participants who experience at least 1 disease flare was calculated. Disease flare is defined as an event determined by the investigator to represent recurrence of Giant Cell Arteritis (GCA) signs or symptoms or an erythrocyte sedimentation rate (ESR) measurement \> 30 mm/hr (attributable to GCA) AND requiring an increase in corticosteroid (CS) dose.
Time frame: Baseline up to Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1; as observed analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + 52-week CS Taper | Percentage of Participants Who Experience at Least 1 Disease Flare Through Week 52 | 55.6 percentage of participants |
| 7.5 mg Upadacitinib + 26-week CS Taper | Percentage of Participants Who Experience at Least 1 Disease Flare Through Week 52 | 41.3 percentage of participants |
| 15 mg Upadacitinib + 26-week CS Taper | Percentage of Participants Who Experience at Least 1 Disease Flare Through Week 52 | 34.3 percentage of participants |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.001495% CI: [0.29, 0.74]Stratified Test for Odds Ratio
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.063395% CI: [0.35, 1.03]Stratified Test for Odds Ratio
Secondary
Rate of Corticosteroid-related Adverse Events Though Week 52
The rate of corticosteroid-related adverse events was calculated, and was adjusted by duration of study drug exposure.
Time frame: Baseline up to Week 52
Population: Safety Analysis Set in Period 1: all participants who received at least 1 dose of study drug in Period 1
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + 52-week CS Taper | Rate of Corticosteroid-related Adverse Events Though Week 52 | 1.7 CS-related AE per participant per year |
| 7.5 mg Upadacitinib + 26-week CS Taper | Rate of Corticosteroid-related Adverse Events Though Week 52 | 1.7 CS-related AE per participant per year |
| 15 mg Upadacitinib + 26-week CS Taper | Rate of Corticosteroid-related Adverse Events Though Week 52 | 2.0 CS-related AE per participant per year |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.437195% CI: [0.8, 1.6]Poisson regression model
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.774995% CI: [0.6, 1.4]Poisson regression model
Secondary
Time to First Disease Flare Through Week 52
Disease flare is defined as an event determined by the investigator to represent recurrence of Giant Cell Arteritis (GCA) signs or symptoms or an erythrocyte sedimentation rate (ESR) measurement \> 30 mm/hr (attributable to GCA) AND requiring an increase in corticosteroid (CS) dose.
Time frame: Baseline up to Week 52
Population: Full analysis set in Period 1 (FAS1): all randomized participants who received at least 1 dose of study drug in Period 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + 52-week CS Taper | Time to First Disease Flare Through Week 52 | 323.0 days |
| 7.5 mg Upadacitinib + 26-week CS Taper | Time to First Disease Flare Through Week 52 | NA days |
| 15 mg Upadacitinib + 26-week CS Taper | Time to First Disease Flare Through Week 52 | NA days |
Comparison: 15 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.002595% CI: [0.399, 0.826]Log-rank test
Comparison: 7.5 mg Upadacitinib + 26-week CS taper vs Placebo + 52-week CS taperp-value: =0.177895% CI: [0.499, 1.136]Log-rank test