| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 |
|
| 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. |
|
| 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 in participants with GCA
To demonstrate the superior efficacy of 300 mg based on:
- Time to clinical failure through Week 52
- Cumulative GC dose through Week 52
To demonstrate the superior efficacy of 150 mg based on:
- Sustained remission at Week 52
- Time to clinical failure through Week 52
- Cumulative GC dose through Week 52
To demonstrate the superior effect on participant's QoL of 300 or 150
mg:
- Based on change of SF-36 score (PCS) at Week 52
To demonstrate the superior effect of 300 or 150 mg based on change in Glucocorticoid Toxicity Index (GTI) at Week 52
To demonstrate the superior effect of 300 or 150 mg on participant's QoL in participants with GCA based on change in:
- FACIT-Fatigue score at Week 52
To evaluate the safety and tolerability of secukinumab |
|
| 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 MRI/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 Magnetic Resonance Imaging
(MRI)/Magnetic Resonance Angiography (MRA) substudy at Screening and Week 52 |
|
| 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, 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).
- 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.
- Active disease as defined by meeting both of the following within 6
weeks of Baseline:
- Presence of signs or symptoms attributed to active GCA and not
related to prior damage (e.g., visual field loss that occurred prior to 6
weeks before Baseline without worsening occurring within 6 weeks of
baseline)
- Elevated erythrocyte sedimentation rate (ESR) ≥ 30 mm/hr or Creactive protein (CRP) ≥ 10 mg/L attributed to active GCA or active GCA on TAB or on imaging study
- Participants to meet definition of new-onset GCA or relapsing GCA:
- Definition of new-onset GCA: GCA diagnosis within 6 weeks of
Baseline visit
- Definition relapsing GCA: GCA diagnosed > 6 weeks before
Baseline 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 the date when GC
therapy was initiated.
- 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 .
- Patients taking MTX (≤ 25 mg/week) are allowed to continue their
medication provided they have taken it for at least 2 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. |
|
| E.4 | Principal exclusion criteria |
-Pregnant or nursing (lactating) women confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
-Women of childbearing potential 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)
-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 a clinical trial where the outcome of treatment with the GCA drug is unknown
- 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 in which patient did not respond to
treatment or experienced a relapse while on that treatment any time
before Baseline. This also includes patients who were treated in a clinical trial for GCA
-Patients treated with i.v. immunoglobulins or plasmapheresis within 8
weeks prior to Baseline
-Patients treated 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
-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 or anticipated to require systemic chronic
glucocorticoid therapy or pulses of glucocorticoids for reasons other
than GCA (e.g. COPD, asthma)at screening or randomization
-Patients requiring chronic (i.e., not occasional "prn") high potency
opioid analgesics for pain management
-Use of other investigational drugs within 5 half-lives of enrollment or
within 30 days (e.g. small molecules) or until the expected
pharmacodynamic effect has returned to BSL (e.g., biologics), whichever is longerBSL; or longer if required by local regulations
-History of hypersensitivity or contraindication to any of the study
treatments or its excipients or to drugs of similar chemical classes
-Active inflammatory bowel disease or other ongoing inflammatory
diseases other than GCA that might confound the evaluation of the
benefit of secukinumab therapy, including or uveitis at screening or
randomization
-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 (e.g., denosumab, TNFα inhibitors) within 4 weeks
or within 5 half-lives of the drug (whichever is longer) prior to BSL, or
anticipated use of a biologic prior to end of study.
- Significant medical problems or diseases, including but not limited to
the following: uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart Association (NYHA) status of class III or IV) and uncontrolled diabetes mellitus
-History of clinically significant liver disease or liver injury as indicated
by abnormal liver function tests (LFTs) such as Aspartate Aminotransferase (AST), alanine aminotransferase (ALT), alkaline
phosphatase (ALP) or serum bilirubin
-WBC count < 3,000/μL, or platelets < 100,000/μL or neutrophils <
1,500/μL or Hgb < 8.3 g/dL (83 g/L).
-Active infections during the last 2 weeks prior to randomization
-History of ongoing, chronic or recurrent infectious disease or evidence of of tuberculosis infection
-Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
-History of lymphoproliferative disease or any known malignancy or
history of malignancy of any organ system within the past 5 years
-Live vaccinations within 6 weeks prior to Baseline or planned
vaccination during study participation until 12 weeks after last study
treatment administration
-Donation or loss of 400 mL or more of blood within 8 weeks before
randomization
-Specific for MRI/MRA imaging sub-study: absolute contraindications to MRI/MRA and to the use of gadolinium-based agents; patients with
severe renal disease, or acutely deteriorating renal function, who would be at risk of nephrogenic systemic fibrosis |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Time to clinical failure
2. Cumulative GC dose
3. Sustained remission at Week 52
4. Change in SF-36 score (PCS)
5. Change in Glucocorticoid Toxicity Index (GTI) as measured by the
Aggregate Improvement Score
6. Change in FACIT-Fatigue Score
7. Safety and Tolerability assessed by adverse events, serious adverse
events, and clinically significant changes in laboratory and vital sign
assessment |
|
| 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 |
|
| 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 MRI/MRA Imaging Sub-Study |
|
| 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 | 3 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 54 |
| 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 |
| Argentina |
| Chile |
| Guatemala |
| Switzerland |
| Australia |
| Brazil |
| Canada |
| Israel |
| Russian Federation |
| South Africa |
| United Kingdom |
| United States |
| Austria |
| Belgium |
| Bulgaria |
| Czechia |
| Denmark |
| Estonia |
| Finland |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Norway |
| Poland |
| Portugal |
| Spain |
| Sweden |
| Türkiye |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 23 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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