Study of efficacy and safety of secukinumab 300 mg and 150 mg in patients with giant cell arteritis (GCA).

• Register: EUCTR
• Last refreshed on: 22 July 2024
• Main ID: EUCTR2020-004809-31-NO
• Date of registration: 28/06/2021
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: Study of efficacy and safety of secukinumab 300 mg and 150 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 and 150 mg administered subcutaneously versus placebo, in combination with a glucocorticoid taper regimen, in patients with giant cell arteritis (GCA (GCAptAIN)
• Date of first enrolment: 16/11/2021
• Target sample size: 349
• 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: 3
• 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, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Hungary, Israel, Italy, Norway, Poland, Portugal, Russian Federation, South Africa, Spain, Sweden, Switzerland, Türkiye, United Kingdom, United States

Contacts

• Name: Medisinsk informasjon
• Affiliation: Novartis Norge AS

• Name: Medisinsk informasjon
• Affiliation: Novartis Norge AS

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, 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 longer BSL; 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.
- Significant medical pr

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: Cosentyx 300 mg solution for injection in pre-filled syringe
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: 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, 1 mg
Product Name: Prednisone
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, 2.5 mg
Product Name: Prednisone
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, 5 mg
Product Name: Prednisone
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, 10 mg
Product Name: Prednisone
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg

Primary Outcome(s)

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.

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

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 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
- EQ-5D score at Week 52
To evaluate the safety and tolerability of secukinumab

Primary end point(s): Sustained remission

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. Sustained remission at Week 52
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
7. Safety and Tolerability assessed by adverse events, serious adverse
events, and clinically significant 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: 16/11/2021
Contact: