E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018250 |
E.1.2 | Term | Giant cell arteritis |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to demonstrate that the efficacy of secukinumab 300 mg s.c. in combination with a 26-week Glucocorticoids (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. |
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E.2.2 | Secondary objectives of the trial |
*All assessments made with secukinumab in combination with a 26-week GC taper regimen compared to placebo in combination with a 52-week GC taper regimen
To assess the efficacy, in participants with GCA: based on:
- Time to clinical failure through Week 52
- Cumulative GC dose through Week 52
To assess the effect on participant's QoL in participants with:
- GCA based on change of SF-36 score (PCS) at Week 52
To assess the effect in participants with GCA based on change in Glucocorticoid Toxicity Index (GTI) at Week 52
To assess the effect on participant's QoL in participants with GCA based on change in:
- FACIT-Fatigue score at Week 52
- EQ-5D score at Week 52
To evaluate the safety and tolerability of secukinumab |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional MRA Imaging Sub-Study
To assess the efficacy of secukinumab in combination with a 26-week glucocorticoid (GC) taper regimen compared to placebo in combination with a 52 week GC taper regimen, based on improvement in signs of vascular inflammation in an optional imaging Magnetic Resonance Angiography (MRA) substudy at Screening and Week 52 |
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E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study must meet all of the following criteria:
- Signed informed consent must be obtained prior to participation in the study.
- Patient must be able to understand and communicate with the investigator and comply with the requirements of the study.
- Male or non-pregnant, non-lactating female patients at least 50 years of age.
- Diagnosis of GCA based on meeting all of the following criteria:
- Age at onset of disease ≥ 50 years.
- Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon
mastication), and/or 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).
- Temporal artery biopsy (TAB) revealing features of GCA and/or cross-sectional imaging study such as ultrasound (e.g. cranial or axillary), MRA, CTA, or PET-CT with evidence of vasculitis.
- Active disease as defined by meeting both of the following within 6 weeks of Baseline:
- Presence of signs or symptoms of GCA
- Elevated erythrocyte sedimentation rate (ESR) ≥ 30 mm/hr or C-reactive protein (CRP) ≥ 10 mg/L attributed to active GCA or active GCA on TAB or imaging study
- Patients to meet definition of new-onset GCA or relapsing GCA:
- Definition of new-onset GCA: diagnosis of GCA within 6 weeks of Baseline visit
- Definition relapsing GCA: diagnosis of GCA > 6 weeks before Baseline visit and patient has experienced recurrence of active disease following the institution of a treatment.
- Patients must be eligible to receive prednisone (or equivalent) 20 mg-60 mg daily at Baseline.
- Patients taking MTX (≤ 25 mg/week) are allowed to continue their medication provided they have taken it for at least 3 months, are on a stable dose for at least 4 weeks prior to randomization, and if they are on stable folic acid treatment before randomization. |
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E.4 | Principal exclusion criteria |
Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor.
- Patients treated with any cell-depleting therapies.
- Previous participation in clinical trial for GCA.
- 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 Baseline.
- 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 Baseline, or if patient did not respond to or experienced a relapse during treatment any time before Baseline.
- Any treatment received for GCA other than GCs and patient did not respond to treatment or experienced a relapse during treatment any time before Baseline.
- Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to Baseline.
- Patients treated with cyclophosphamide, tacrolimus, everolimus, hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine, mycophenolate mofetil within 6 months prior to Baseline.
- Patients treated with leflunomide within 8 weeks of Baseline unless a cholestyramine washout has been performed in which case the patient must be treated within 4 weeks of Baseline.
- Patients treated with an alkylating agent within 5 years prior to Baseline, unless specified in other exclusion criteria.
- Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA.
- Receipt of > 100 mg daily intravenous methylprednisolone pulse therapy within 6 weeks prior to Baseline.
- Patients requiring chronic (i.e., not occasional “prn”) high potency opioid analgesics for pain management.
- Patients treated with any investigational agent within 4 weeks or within 5 half lives of the drug (whichever is longer) prior to Baseline.
- Contraindication or hypersensitivity to secukinumab.
- Active ongoing inflammatory diseases other than GCA that might confound the evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease or uveitis.
- Major ischemic event (e.g. myocardial infarction, stroke, etc.) or transient ischemic attack (TIA) (except ischemia-related vision loss), related or unrelated to GCA, within 12 weeks of screening.
- Confirmed diagnosis of any primary form of systemic vasculitis, other than GCA.
- Any other biologics within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline.
- Active ongoing diseases which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for treatment with immunomodulatory therapy.
- Active systemic infections during the last 2 weeks (exception: common cold) prior to randomization.
- History of ongoing, chronic or recurrent infectious disease or evidence of of tuberculosis infection as defined by a positive QuantiFERON TB- Gold Plus test. Patients with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established then treatment according to local country guidelines must be initiated prior to randomization.
- Live vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Time to clinical failure
2. Cumulative GC dose
3. Change in SF-36 score (PCS)
4. Change in Glucocorticoid Toxicity Index (GTI) as measured by the Aggregate Improvement Score
5. Change in FACIT-Fatigue Score
6. Change in EQ-5D score
7. Safety and Tolerability assessed by adverse events, serious adverse events, and clinically significanct changes in laboratory and vital sign assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.-2. Through Week 52
3.-6. Change at Week 52
7. Trial Duration |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Optional MRA Imaging Sub-Study |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
Guatemala |
New Zealand |
Russian Federation |
South Africa |
Turkey |
United States |
Belgium |
Bulgaria |
Denmark |
Estonia |
Finland |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
Argentina |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |