[M16-852] A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis
[M16-852] A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis
Otani Tetsuya
Abbvie GK
3-1-21 Shibaura, Minato-ku, Tokyo
+81-120-587-874
AbbVie_JPN_info_clingov@abbvie.com
Contact for Patients and HCP
Abbvie GK
3-1-21 Shibaura, Minato-ku, Tokyo
+81-120-587-874
AbbVie_JPN_info_clingov@abbvie.com
completed
Feb. 18, 2019
8
Interventional
Period 1 (52 weeks) Subjects who meet eligibility criteria will be randomized in a 2 to 1 to 1 ratio to 1 of 3 treatment groups.
Upadacitinib 15 mg QD + 26-week CS taper regimen(n =210)
Upadacitinib 7.5 mg QD + 26-week CS taper regimen(n =105)
PBO QD + 52-week CS taper regimen (n = 105)
All subjects will receive CS and will be tapered according to a predefined schedule over a 26- or 52-week period. Open-label prednisolone will be provided until the dose is tapered to 20 mg per day. Subsequently, blinded prednisolone will be provided for the remaining blinded taper regimen.
Period 2 (52 weeks). Subjects who achieved remission for at least 16 weeks prior to the Week 52 visit (at the end of Period 1) will continue in Period 2. Subjects who were assigned to upadacitinib in Period 1 will be re-randomized in a 2 to 1 ratio to either continue on upadacitinib or switch to PBO. Subjects who were assigned to PBO in Period 1 will continue to take placebo.
treatment purpose
3
1. Diagnosis of giant cell arteritis (GCA) according to the following criteria:
- History of erythrocyte sedimentation rate (ESR) >= 50 mm/hour or C-reactive protein (CRP) >= 2.45 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).
2. Active GCA, either new onset or relapsing, within 6 weeks of Baseline.
3. Participants must have initiated 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.
4. 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.
5. Females must either be postmenopausal or permanently surgically sterile or, practicing at least 1 specified method of birth control through the study.
1) Prior exposure to any Janus Kinase (JAK) inhibitor.
2) 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.
3) 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 6 weeks of study start
- Abatacept or Tumor Necrosis Factor (TNF) inhibitors within 8 weeks or study start
- Ustekinumab within 12 weeks of study start
- Cell-depleting agents or alkylating agents including cyclophosphamide within 6 months of study start
4) 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.
5) Female who is pregnant, breastfeeding, or considering pregnancy during the study
50age old over
No limit
Both
Giant Cell Arteritis
investigational material(s)
Generic name etc : ABT-494
INN of investigational material : Upadacitinib
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Oral 7.5mg 15mg
control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -
efficacy
the proportion of subjects achieving sustained remission at Week 52. Sustained remission is defined as having achieved both of the following:
- Absence of GCA signs and symptoms from Week 12 through Week 52
- Adherence to the protocol-defined CS taper regimen.
safety
efficacy
- Proportion of subjects achieving sustained complete remission from Week 12 through Week 52. Sustained complete remission is defined as having achieved all of the following:
--> Absence of GCA signs and symptoms from Week 12 through Week 52
--> Normalization of erythrocyte sedimentation rate ((ESR) to less than 30 without elevation to more than 30 (attributable to GCA)) from Week 12 through Week 52.
--> Normalization of C-reactive protein ((CRP) to less than 1 without elevation to more than 1 (attributable to GCA)) from Week 12 through Week 52.
--> and Adherence to the protocol-defined CS taper regimen.
- Cumulative CS exposure.
- 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 more than 30 (attributable to GCA), AND requiring an increase in CS dose.
- Proportion of subjects who experience at least 1 disease flare through Week 52.
- Proportion of subjects in complete remission at Week 52. Complete remission is defined as having achieved all of the following.
--> Absence of GCA signs and symptoms.
--> Normalization of ESR to >= 30.
--> Normalization of CRP to >= 1. and
--> Adherence to the protocol-defined CS taper regimen.
- Proportion of subjects in complete remission at Week 24.
- Change from Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) at Week 52.
- Number of disease flares per subject during Period 1.
- Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 52.
- Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 52.
- IncidenceRate of CS-related adverse events (AEs).
Abbvie GK
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Abbvie Inc.
Upadacinitib M16-852
Sakai City Medical Center Institutional Review Board
