Giant Cell Arteritis, Polymyalgia Rheumatica
Conditions
Keywords
Giant cell arteritis (GCA), Polymyalgia rheumatica (PMR), Secukinumab, pharmacokinetics, intravenous
Brief summary
This study will examine how intravenous (i.v.) Secukinumab will be processed in the body (pharmacokinetics \[PK\]) and whether it will be safe and tolerable after multiple doses of i.v. Secukinumab infusion in adult patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR).
Detailed description
This is a 12-week, open-label, multicenter, basket design study followed by an 8-week follow-up period in two cohorts of participants, one cohort with GCA and one cohort with PMR. This study will consist of 3 phases: screening, treatment and follow-up. Participants will enter a screening period: up to 6 weeks to assess eligibility \[or up to 8 weeks in the event of a major healthcare disruption or a need to complete screening requirements (e.g., required washouts, TB testing, and work up and treatment as needed per local guidelines. Participants will enter a treatment period of 12 weeks: 2 cohorts (GCA and PMR cohorts) receiving total of 3 i.v. doses of Secukinumab (Week 0, Week 4 and Week 8). After treatment participants will enter a follow-up period: 8 weeks treatment-free follow-up (12 weeks after last dose of study treatment). The total duration of the trial for a participant (from screening to follow up) is approximately 26 weeks (maximum of approximately 28 weeks) including safety follow-up.
Interventions
DRUGSecukinumab
Intravenous (i.v.) doses of Secukinumab at Week 0, Week 4 and Week 8
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
30 patients per cohort (Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PRM) are planned to be enrolled
Eligibility
Sex/Gender
ALL
Age
50 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Inclusion Criteria for GCA: 1. Male or non-pregnant, non-lactating female participants at least 50 years of age 2. Diagnosis of GCA based on meeting all of the following criteria: * Unequivocal cranial symptoms of GCA (e.g., new-onset localized headache, scalp or temporal artery tenderness, permanent or temporary ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication), and/or unequivocal symptoms of PMR (defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness) and/or symptoms of limb ischemia (claudication) * Temporal artery biopsy (TAB) revealing features of GCA and/or cross-sectional imaging study such as ultrasound (e.g., cranial or axillary), MRI/MRA, CTA, or PET-CT with evidence of vasculitis 3. Active GCA disease within 6 months prior to Baseline as defined by meeting both of the following: * Presence of signs or symptoms attributed to active GCA and not related to prior damage (e.g., vision loss that occurred without new findings) * Elevated ESR \>= 30 mm/hr or CRP \>= 10 mg/L attributed to active GCA or active GCA on TAB or on imaging study Inclusion Criteria for PMR: 1. Male or non-pregnant, non-lactating female participants at least 50 years of age 2. Diagnosis of PMR according to the provisional ACR/EULAR classification criteria: Participants \>= 50 years of age with a history of bilateral shoulder pain accompanied by elevated CRP concentration (\>= 10 mg/L) and/or elevated ESR (\>= 30 mm/hr) who scored at least 4 points from the following optional classification criteria: * Morning stiffness \>45 min (2 points) * Hip pain or restricted range of motion (1 point) * Absence of rheumatoid factor and/or anti-citrullinated protein antibodies (2 points) * Absence of other joint involvement (1 point) 3. Active PMR disease within 6 months prior to Baseline as defined by signs and symptoms attributable to PMR meeting the following: * Bilateral shoulder girdle and/or bilateral hip girdle pain associated with inflammatory stiffness with or without additional symptoms indicative of a PMR relapse (such as constitutional symptoms) that are in the opinion of the Investigator not due to other diseases that may mimic PMR such as osteoarthritis in shoulders or hips, polyarticular calcium pyrophosphate deposition disease, rotator cuff disease, adhesive capsulitis (frozen shoulder) or fibromyalgia Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Secukinumab: Maximum concentration at steady state (Cmax,ss) | Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime | Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Maximum concentration at steady state (Cmax,ss) will be listed and summarized using descriptive statistics. |
| Secukinumab: Minimum concentration at steady state (Cmin,ss) | Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime | Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Minimum concentration at steady state (Cmin,ss) will be listed and summarized using descriptive statistics. |
| Secukinumab: Area under the concentration-time curve at steady state during a dosing interval (AUCtau,ss) | Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime | Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Area under the concentration-time curve at steady state during a dosing interval (AUCtau,ss) will be listed and summarized using descriptive statistics. |
| Secukinumab: Average concentration at steady state (Cavg,ss [=AUCtau,ss/tau]) | Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime | Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Average concentration at steady state (Cavg,ss \[=AUCtau,ss/tau\]) will be listed and summarized using descriptive statistics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment Emergent Adverse Events | Up to 12 weeks after last dose administration. | The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters. |
| Secukinumab: Clearance (CL) | Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime | Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Clearance (CL) will be listed and summarized using descriptive statistics. |
| Secukinumab: Volume of distribution at steady state (Vss) | Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime | Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Volume of distribution at steady state (Vss) will be listed and summarized using descriptive statistics. |
Countries
Czechia, Italy, Portugal, Spain, Switzerland, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed