Multicenter, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of Upadacitinib in study participants with giant cell arteritis
Zusammenfassung der Studie
Giant cell arteritis (GCA), also known as temporal arteritis, is a chronic inflammatory disease of the blood vessels, most commonly in the head and neck region. A corticosteroid (CS) therapy currently represents the standard treatment for GCA. Despite alleviating many symptoms, prolonged CS therapy can cause unwanted side effects, and inflammation may still persist in some patients. Therefore, there is a need for improved treatment options. Upadacitinib is an investigational drug currently being developed for the treatment of adult patients with inflammatory diseases such as GCA. This study investigates how well Upadacitinib works in combination with CS in the body and how safe it is compared to placebo (an inactive substance) in treating adult patients aged at least 50 years with GCA. The CS dose will be gradually reduced over the course of the study, a process known as tapering.
(BASEC)
Untersuchte Intervention
Approximately n=420 study participants will be enrolled at about 140 study centers worldwide.
The study is divided into two phases. In phase 1, participants will be randomly assigned to three treatment arms over a period of 52 weeks:
• Upadacitinib Dose A 1x/day + 26-week CS tapering schedule
• Upadacitinib Dose B 1x/day + 26-week CS tapering schedule
• Placebo 1x/day + 52-week CS tapering schedule
Patients who show no signs or symptoms of GCA at the end of phase 1 will continue to phase 2 for an additional 52 weeks.
The study is blinded, meaning that neither the study participant nor the study physician knows the assigned treatment arm.
Participation may last up to 113 weeks in total. Patients will complete approximately 20 study visits.
(BASEC)
Untersuchte Krankheit(en)
Giant cell arteritis (GCA)
(BASEC)
1. Diagnosis of giant cell arteritis (GCA) based on the following criteria: o Men and women aged at least 50 years o History of ESR ≥ 50 mm/h (erythrocyte sedimentation rate) or CRP ≥ 2.45 mg/dl (C-reactive protein) o At least one of the following criteria must be met: clear cranial symptoms of GCA or clear symptoms of polymyalgia rheumatica (PMR) o Presence of at least one of the following: temporal artery biopsy showing features of GCA or signs of vascular vasculitis based on angiography or imaging techniques such as ultrasound, MRI, CT, or PET. 2. Active GCA, either newly diagnosed or recurrent with active disease within 6 weeks prior to baseline. 3. Participants must have started treatment with ≥40 mg prednisone (or an equivalent medication) at any time prior to baseline and be using ≥ 20 mg prednisone (or equivalent) 1x/day at baseline. 4. Participants must have GCA that, in the opinion of the investigator, is clinically stable, so that the corticosteroid tapering schedule defined in the protocol can be safely initiated. 5. Women must be either postmenopausal or permanently surgically sterile or using at least one established contraceptive method. (BASEC)
Ausschlusskriterien
1. Prior treatment with a Janus kinase (JAK) inhibitor. 2. Treatment with an interleukin-6 (IL-6) inhibitor within 4 weeks prior to study initiation or prior treatment with an IL-6 inhibitor that resulted in an inflammatory flare during treatment. 3. Use of any of the following systemic immunosuppressants within the specified time frame prior to study initiation: o Anakinra within one week after study initiation o Methotrexate, hydroxychloroquine, cyclosporine, azathioprine, or mycophenolate within 4 weeks prior to study initiation o Oral corticosteroid (CS) for conditions other than GCA within 4 weeks after study initiation or intravenous CS within 6 weeks after study initiation o Abatacept or tumor necrosis factor (TNF) inhibitors within 8 weeks prior to baseline. o Ustekinumab within 12 weeks prior to baseline o Cytotoxic agents or alkylating agents including cyclophosphamide within 6 months prior to study initiation 4. Current or past infection including herpes zoster or herpes simplex, HIV, active tuberculosis, active or chronic recurrent infection, active hepatitis B or C. (BASEC)
Studienstandort
Basel, Bern, Freiburg, St Gallen
(BASEC)
Sponsor
AbbVie AG Cham
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
AbbVie Medical Information
+41 41 399 16 89
medinfo.ch@clutterabbvie.comAbbVie AG
(BASEC)
Allgemeine Auskünfte
AbbVie
(ICTRP)
Wissenschaftliche Auskünfte
AbbVie
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Ostschweiz EKOS
(BASEC)
Datum der Bewilligung durch die Ethikkommission
28.03.2019
(BASEC)
ICTRP Studien-ID
NCT03725202 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
M16-852: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects with Giant Cell Arteritis (BASEC)
Wissenschaftlicher Titel
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis: SELECT-GCA (ICTRP)
Öffentlicher Titel
A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (ICTRP)
Untersuchte Krankheit(en)
Giant Cell Arteritis (GCA) (ICTRP)
Untersuchte Intervention
Drug: UpadacitinibDrug: Corticosteroid (CS)Other: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Percentage of Participants Achieving Sustained Remission at Week 52 (ICTRP)
Percentage of Participants Achieving Sustained Complete Remission From Week 12 Through Week 52;Cumulative Corticosteroid (CS) Exposure Through Week 52;Time to First Disease Flare Through Week 52;Percentage of Participants Who Experience at Least 1 Disease Flare Through Week 52;Percentage of Participants in Complete Remission at Week 52;Percentage of Participants in Complete Remission at Week 24;Change From Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 52;Number of Disease Flares Per Participant Through Week 52;Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) at Week 52;Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale at Week 52;Rate of Corticosteroid-related Adverse Events Though Week 52 (ICTRP)
Registrierungsdatum
27.10.2018 (ICTRP)
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
ABBVIE INC., AbbVie (ICTRP)
Sekundäre IDs
2023-505476-29-00, 2017-003978-13, M16-852 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT03725202 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar