Study of efficacy and safety of secukinumab 300 mg in patients with giant cell arteritis (GCA).

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2020-004809-31-IT
• Date of registration: 22/10/2021
• Prospective Registration: No
• Primary sponsor: NOVARTIS PHARMA AG
• Public title: Study of efficacy and safety of secukinumab 300 mg in patients with giant cell arteritis (GCA).
• Scientific title: A randomized, parallel-group, double-blind, placebo-controlled, multicenter Phase III trial to investigate the efficacy and safety of secukinumab 300 mg administered subcutaneously versus placebo, in combination with a glucocorticoid taper regimen, in patients with giant cell arteritis (GCA) - -
• Date of first enrolment: 16/09/2021
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004809-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Guatemala, Hungary, Italy, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Regulatory Affairs
• Affiliation: Novartis Farma S.p.A.

• Name: Regulatory Affairs
• Affiliation: Novartis Farma S.p.A.

Key inclusion & exclusion criteria

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 Creactive 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.
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 163
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 77

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 TBGold 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Giant cell arteritis
MedDRA version: 23.1 Level: PT Classification code 10018250 Term: Giant cell arteritis System Organ Class: 10047065 - Vascular disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Prednisone
Product Name: Prednisone
Product Code: [-]
Pharmaceutical Form:
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Current Sponsor code: -
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Prednisone
Product Name: Prednisone
Product Code: [-]
Pharmaceutical Form:
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Current Sponsor code: -
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Prednisone
Product Name: Prednisone
Product Code: [-]
Pharmaceutical Form:
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Current Sponsor code: -
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2500-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Prednisone
Product Name: Prednisone
Product Code: [-]
Pharmaceutical Form:
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Current Sponsor code: -
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Cosentyx
Product Name: Cosentyx
Product Code: [AIN457]
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: 300-
Pharmaceutical form of the placebo: Solution for injection in pre-fi

Primary Outcome(s)

Secondary Objective: *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

Main Objective: 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.

Primary end point(s): Sustained remission

Timepoint(s) of evaluation of this end point: Week 52

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1.-2. Through Week 52
3.-6. Change at Week 52
7. Trial Duration

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

Secondary ID(s)

CAIN457R12301

2020-004809-31-FR

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 14/07/2021
Contact: