Efficacy and Safety of secukinumab in patients with new onset of giant cell arteritis who are in clinical remission

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

21 Sep 2022 → 24 Feb 2026

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma GmbH

External identifiers

EU CT number

2024-512856-40-00

EudraCT number

2021-002622-24

ClinicalTrials.gov

NCT05380453

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate the superiority of secukinumab 300 mg s.c. compared to placebo (both arms in combination with a prednisolone or equivalent taper regimen as per treatment guideline) in delaying the time to first GCA clinical relapse in patients with new-onset GCA who are in clinical remission and eligible for treatment with glucocorticoid-monotherapy

Secondary objectives 3

1. To demonstrate the superiority of secukinumab 300 mg s.c. compared to placebo, measured by the proportion of participants in sustained clinical remission+ at Week 52
2. To assess the effect of secukinumab 300 mg s.c. compared to placebo measured by: - Disease activity and quality of life measures at Week 52 for patient global assessment (PGA) of disease activity using a visual analogue scale (VAS), patient assessment of pain using a numeric rating scale (NRS), Short form 36 (SF-36 PCS and MCS) and other assessments - Time to reach prednisolone or equivalent dose below Cushing threshold of ≤7.5 mg/day - Proportion of participants on prednisolone or equivalent dose below Cushing threshold of ≤7.5 mg/day at Week 52 - Cumulative prednisolone or equivalent dose through Week 52
3. To evaluate safety and tolerability of secukinumab 300 mg s.c. in participants with GCA who are eligible for treatment with glucocorticoid monotherapy

Conditions and MedDRA coding

Giant Cell Arteritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed informed consent must be obtained prior to participation in the study
2. Participant must be able to understand and communicate with the investigator and comply with the requirements of the study
3. Male or female participants at least 50 years of age
4. Diagnosis of new-onset GCA, defined as GCA diagnosed within 6 weeks of baseline (BSL) visit, based on meeting all of the following criteria: - Age at onset of disease ≥50 years. - History of Erythrocyte Sedimentation Rate (ESR) ≥30 mm/hr or C-reactive protein (CRP) ≥10 mg/L attributable to active GCA. - 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 revealing features of GCA AND/OR evidence of vasculitis in cranial or extracranial arteries by angiography or cross-sectional imaging study such as ultrasound, magnetic resonance angiography (MRA), computed tomography angiography (CTA), positron emission tomography - computed tomography (PET-CT)
5. Participants must be in clinical remission at BSL
6. Participants with no relapsing GCA at BSL
7. Prednisolone or equivalent dose (oral) of 20-60 mg/day or equivalent dose of other glucocorticoids (GCs) at BSL

Exclusion criteria 25

1. Participants not eligible for glucocorticoid monotherapy due to known increased risk for or presence of GC-related adverse-effects or complications and/or intolerance to GCs, such as osteoporosis, diabetes mellitus, cardiovascular disease and glaucoma as assessed at the investigator’s discretion.
2. Previous exposure to secukinumab or another biologic drug directly targeting IL-17 or IL-17 receptor.
3. Participants treated with any cell-depleting therapies including but not limited to anti- CD20 or investigational agents (e.g., anti-CD3, anti-CD4, anti-CD5 or anti-CD19).
4. Previous participation in clinical trials for GCA
5. Participants who have been treated with inhibitors directly targeting IL-12 and/or IL-23 (such as ustekinumab, guselkumab, tildrakizumab, risankizumab), IL-1 or IL-1 receptor (such as anakinra or canakinumab), or abatacept within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL.
6. 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 BSL, or if participant did not respond to or experienced a clinical relapse during treatment any time before BSL.
7. Any treatment received for GCA other than GCs and participant did not respond to treatment or experienced a clinical relapse during treatment any time before BSL.
8. Any other biologics within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL.
9. Participants treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to BSL.
10. Participants treated with cyclophosphamide, tacrolimus, everolimus hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine, mycophenolate mofetil within 6 months prior to BSL.
11. Participants treated with methotrexate (MTX), within 4 weeks prior to BSL.
12. Participants treated with leflunomide within 8 weeks prior to BSL unless a cholestyramine washout has been performed in which case the participant must be treated within 4 weeks of BSL.
13. Participants treated with an alkylating agent within 5 years prior to Baseline, unless specified in other exclusion criteria.
14. Participants requiring systemic chronic glucocorticoid therapy for any other reason than GCA at Screening.
15. Participants requiring chronic (i.e., not occasional “prn”) high potency opioid analgesics for pain management.
16. Participants treated with any investigational agent within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to BSL.
17. Contraindication or hypersensitivity to secukinumab.
18. Active ongoing inflammatory diseases other than GCA that might confound the evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease or uveitis.
19. Active ongoing diseases which in the opinion of the investigator immunocompromises the participant and/or places the participant at unacceptable risk for treatment with immunomodulatory therapy.
20. Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunocomprises the participant and/or places the participant at unacceptable risk for participation in an immunomodulatory therapy.
21. 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.
22. Confirmed diagnosis of any primary form of systemic vasculitis, other than GCA.
23. Active systemic infections during the last 2 weeks (exception: common cold) prior to BSL.
24. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Plus test. Participants with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the participant 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 BSL.
25. Live vaccinations within 6 weeks prior to BSL or planned live vaccination during study participation until 12 weeks after last study treatment administration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time from baseline to first GCA clinical relapse

Secondary endpoints 3

1. Proportion of participants in sustained clinical remission at Week 52
2. Efficacy endpoints: - Changes from Baseline to Week 52 in disease activity and quality of life for each of the following: PGA score (VAS), SF-36 (PCS and MCS) score, Patient assessment of pain (NRS) and other assessments - Time from Baseline to reach prednisolone or equivalent dose below ≤7.5 mg/day - Proportion of participants on prednisolone or equivalent dose below Cushing threshold of ≤7.5 mg/day at Week 52 - Cumulative prednisolone or equivalent dose through Week 52
3. Safety and tolerability assessments over time: incidence and severity of AEs and SAEs; routine safety laboratory parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma GmbH

Sponsor organisation

Novartis Pharma GmbH

Address

Sophie-Germain-Strasse 10

City

Nuremberg

Postcode

90443

Country

Germany

Scientific contact point

Organisation

Novartis Pharma GmbH

Contact name

Medizinischer Infoservice (MCC)

Public contact point

Organisation

Novartis Pharma GmbH

Contact name

Medizinischer Infoservice (MCC)

Third parties 5

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications