Giant Cell Arteritis (GCA)
Conditions
Keywords
GCA, temporal arteritis, giant cell arteritis, vasculitis, secukinumab, monoclonal antibody, AIN457, prednisone taper regimen, glucocorticoid, GC
Brief summary
This is a phase III study of efficacy and safety of secukinumab versus placebo, in combination with glucocorticoid taper regimen, in patients with giant cell arteritis (GCA)
Detailed description
Randomized, parallel-group, double-blind, placebo-controlled, multi-center, Phase III study to evaluate the efficacy and safety of secukinumab 300 mg and 150 mg administered subcutaneously versus placebo, in combination with a glucocorticoid taper regimen, in patients with giant cell arteritis (GCA) (GCAptAIN)
Interventions
BIOLOGICALSecukinumab 300 mg
Secukinumab 300 mg
OTHERPlacebo
Placebo
BIOLOGICALSecukinumab 150 mg
Secukinumab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
50 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study. 2. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study. 3. Male or non-pregnant, non-lactating female patients at least 50 years of age. 4. Diagnosis of GCA based on meeting all of the following criteria: * Age at onset of disease ≥ 50 years. * 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 polymyalgia rheumatica (PMR) (defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness) and/or symptoms of limb ischemia (claudication). * 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. 5. Active disease as defined by meeting both of the following within 6 weeks of BSL (see Section 8.1 for details) * Presence of signs or symptoms attributed to active GCA and not related to prior damage (e.g., visual loss that occurred prior to 6 weeks before BSL without new findings occurring within 6 weeks of BSL) * Elevated ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L attributed to active GCA or active GCA on TAB or on imaging study. 6. Patients to meet definition of new-onset GCA or relapsing GCA: * Definition of new-onset GCA\*: GCA that is diagnosed within 6 weeks of BSL visit * Definition relapsing GCA: GCA diagnosed \> 6 weeks before BSL visit and following institution of an appropriate treatment course for GCA, participant has experienced recurrence of active symptoms or signs of disease after resolution. * The 6-week timeframe is to be calculated from the date of suspected GCA diagnosis. Suspected diagnosis is defined as date when GC therapy was initiated. 7. Patients' current GCA episode should be treatable with a dose of prednisone (or equivalent) designed to adequately achieve disease control in accordance with international guidelines. If this is not possible due to concerns regarding GC toxicity, the patient should not be enrolled. It must be medically appropriate for the patient to receive prednisone (or equivalent) 20 mg-60 mg daily (or equivalent) at BSL. 8. Patients taking MTX (≤ 25 mg/week) are allowed to continue their medication provided they have taken it for at least 2 months and are on a stable dose for at least 4 weeks prior to randomization and if they are on stable folic acid treatment before randomization.
Exclusion criteria
1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. 2. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during study treatment or longer if required by locally approved prescribing information (e.g., in European Union (EU) 20 weeks after treatment discontinuation). Also, contraception should be used in accordance with locally approved prescribing information of concomitant medications administered (e.g., Rescue Treatment). Effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. * Bilateral oophorectomy with or without hysterectomy, total hysterectomy or bilateral salpingectomy at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment are they not considered to be of child-bearing potential. * Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks before taking study treatment. * Male sterilization (vasectomy) of male partner(s) of the female participant at least 6 months prior to screening. * Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). NOTE: for United Kingdom: with spermicidal foam/gel/film/cream/vaginal suppository. * Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example, hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. * Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms). Women participants are considered not of child-bearing potential if they are post-menopausal or have had, surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks prior to first dose of study treatment in the study . In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered to be not of child-bearing potential. If local regulations are more stringent than the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF). 3. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor. 4. Patients treated with any cell-depleting therapies. 5. Previous participation in a clinical trial where the outcome of treatment with the GCA drug is unknown. This does not include trials where the treatment for GCA was GCs, MTX, leflunomide or azathioprine 6. Patients who have been treated with inhibitors directly targeting IL-1, or IL-1 receptor, IL-12 and IL-23, or abatacept within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL. 7. Treatment with tocilizumab, other IL-6/IL6-R inhibitor or JAK inhibitor within 12 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL, or if the patient did not respond to or experienced a relapse during treatment any time before BSL. 8. Any treatment received for GCA in which patient did not respond to treatment or experienced a relapse while on that treatment any time before BSL. This also includes patients who were treated in a clinical trial for GCA. Patients who failed on treatment with GCs, MTX, leflunomide and/or azathioprine may be included. 9. Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to BSL. 10. Patients treated (i.e. systemic therapy) with cyclophosphamide or hydroxychloroquine within 6 months prior to BSL, or tacrolimus, everolimus, cyclosporine A, azathioprine, sulfasalazine, mycophenolate mofetil within 4 weeks prior to BSL. 11. Patients treated with leflunomide within 8 weeks of BSL unless a cholestyramine washout has been performed in which case the patient must be treated within 4 weeks of BSL. 12. Patients treated with an alkylating agent within 5 years prior to BSL, unless specified in other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with sustained remission | 52 weeks | Primary objective is to determine whether the efficacy of secukinumab 300 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week glucocorticoids (GC) taper regimen in participants with giant cell arteritis (GCA) based on sustained remission at Week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative GC Dose | 52 weeks | To demonstrate that the efficacy of secukinumab 300 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, in participants with GCA, based on cumulative GC dose through Week 52 |
| Proportion of participants with sustained remission | 52 weeks | To demonstrate that the efficacy of secukinumab 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen in participants with GCA based on sustained remission at Week 52 |
| Time to first use of Escape or Rescue Treatment due to GCA as measured in days | 52 weeks | To demonstrate that the efficacy of secukinumab 300 mg s.c. or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen in participants with GCA based on time to first use of Escape Treatment or Rescue Treatment due to GCA |
| Change in SF-36 score (PCS) | 52 weeks | To demonstrate that the effect on participant's QoL of secukinumab 300 mg s.c. or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, in participants with GCA based on change of SF-36 score (PCS) at Week 52 |
| Glucocorticoid Toxicity Index (GTI) as measured by the Aggregate Improvement Score (AIS) | 52 weeks | To demonstrate that the effect of secukinumab 300 mg s.c. or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, in participants with GCA based on Glucocorticoid Toxicity Index (GTI) |
| Change in FACIT-Fatigue Score | 52 weeks | To demonstrate that the effect on participant's QoL of secukinumab 300 mg s.c. or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, in participants with GCA based on change in FACIT-Fatigue score at Week 52 |
| Number of participants with Adverse events (AEs) and Serious AEs (SAEs) | 52 weeks | Number of participants with AEs and SAEs as a measure of safety and tolerability |
| Number of participants with clinically significant changes in clinical laboratory measures and vital signs | 52 weeks | Number of participants with clinically significant changes in clinical laboratory measures and vital signs, as assessed by the Investigator |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Hungary, Israel, Italy, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed