Phase-III-Studie zur Wirksamkeit und Sicherheit von Secukinumab im Vergleich zu Placebo in Kombination mit Glukokortikoid-Ausschleichung bei Teilnehmenden mit Riesenzellarteriitis (RZA)

Trade Name: Cosentyx 300mg solution for injection in pre-filled syringe
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SECUKINUMAB
CAS Number: 1229022-83-6
Current Sponsor code: AIN457
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: PredniSONE Tablets USP, 1mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard + tablet
Route of administration of the placebo: Oral use

Trade Name: PredniSONE Tablets USP, 2.5mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule, hard + tablet
Route of administration of the placebo: Oral use

Trade Name: PredniSONE Tablets USP, 5mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard + tablet
Route of administration of the placebo: Oral use

Trade Name: PredniSONE Tablets USP, 20mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard + tablet
Route of administration

Gender:
Female: yes
Male: yes

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 258

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, TNFa 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.
- Significan