STARS (Secukinumab in TAkayasu ARteritiS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-02-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

NOVARTIS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate disease remission (defined by a NIH score ≤ 1) at 6 months in severe TAK patients and with discontinuation of prednisone

Secondary objectives 9

1. To assess the incidence of relapse as defined by NIH criteria ≥ 2 after initiation of treatment. - To assess the incidence of treatment failure after initiation of treatment, i.e., disease persistently active as defined by NIH criteria ≥ 2.
2. To assess the incidence of treatment failure after initiation of treatment, i.e., disease persistently active as defined by NIH criteria ≥ 2.
3. To assess the cumulative dose of prednisone after initiation of experimental therapy.
4. To assess the rate of glucocorticoid-free disease remission in both arms at 3, 6 and 12 months
5. To assess the incidence of adverse events (AE) and serious adverse events (SAE) after initiation of investigational therapy
6. To assess the treatment’s impact in quality of life between the start of investigational therapy and 6 and 12 months after
7. To assess the vascular lesions at 3, 6 and 12 months after the start of experimental treatment
8. To assess the vascular hypermetabolism between the start of experimental treatment and at 6 and 12 months after, as measured by 18-FDG-PET.
9. To assess the incidence of revascularization procedures (endovascular or surgical) required because of Takayasu disease at 6 and 12 months after initiation of experimental treatment

Conditions and MedDRA coding

TAkayasu ARteritiS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patients ≥15 years and Signed informed consent
2. Affiliation with the French national social security system. Patients with AME are eligible
3. Adequate and effective contraceptive measures based on CTFG update of recommendations version 1.1 dated 21-Sep-2020
4. For women of childbearing age, a negative serum or urinary pregnancy test
5. Diagnosis of TAK based on the 2022 American College of Rheumatology/EULAR and/or Ishikawa criteria modified by Sharma
6. Active TAK defined by a National Institutes of Health [NIH] score >1 in the past 2 months
7. Severe TAK, defined as either refractory/relapsing disease or by the presence of severe arterial involvement at baseline
8. Patients must be eligible to receive prednisone (or equivalent) 10-50 mg daily at baseline. Oral corticosteroids must be at a stable dose for at least 2 weeks prior to the first administration of study drug at Day 0.
9. Absence of chronic active infections. Patients with a positive TB test may participate in the study if further work up (according to local practice/guidelines) conclusively establishes that the patient has no evidence of active tuberculosis

Exclusion criteria 10

1. Inability to comply with study guidelines or provide informed consent
2. Pregnancy or breastfeeding
3. History of severe immunosuppression, positive serology for HIV or positive HBsAg
4. Infection requiring treatment with intravenous antibiotics within 2 weeks prior to the inclusion & randomization visit
5. Contraindication or hypersensitivity to Secukinumab, TNF inhibitors or tocilizumab, corticosteroids, TB prophylactic treatment or to any of their excipients
6. Have received live vaccines within 3 months prior to inclusion
7. History of malignancy in the last 5 years (except adequately treated basal or squamous cell carcinoma of the skin)
8. Severe renal impairment (creatinine clearance <30mL/min/1.73m2)
9. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests such as Aspartate Aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) or serum bilirubin. The investigator should be guided by the following criteria: a. SGOT (AST) and SGPT (ALT) may not exceed 3 × the upper limit of normal (ULN). A single parameter elevated up to and including 3 × ULN should be re-checked once more as soon as possible, and in all cases, at least prior to randomization, to rule-out laboratory error. b. Alkaline phosphatase may not exceed 4 × ULN. An elevation up to and including 4 × ULN should be re-checked once more as soon as possible, and in all cases, at least prior to randomization, to rule-out laboratory error. c. Total bilirubin may not exceed 4 × ULN. If the total bilirubin concentration is increased above 4 × ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin
10. Blood count abnormality: a. Platelet count < 50 x 10.3/mm3 b. Neutropenia < 1000/mm3 c. Haemoglobin < 8 g/dl c. Hémoglobine < 8 g/dl

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Disease remission (defined by NIH score ≤ 1) at 6 months and with prednisone discontinuation Disease activity is measured according to National Institutes of Health (NIH) criteria (Kerr 1994) and comprises four variables, each scoring one point as below (scale range 0-4 points). A score equal or superior to 2 is considered as active disease.
2. • Criterion 1 scores if at least one of the following systemic characteristics, without any other cause identified: o Constitutional symptoms such as low-grade fever, weight loss and fatigue; o Extra-vascular manifestations (e.g., polyarthralgia / arthritis, erythema nodosum, episcleritis, etc).
3. • Criterion 2 scores if at least one of the following clinical signs have appeared since the previous visit: o New carotidodynia, vascular claudication or pain along an arterial pathway o New transient ischemic attack (TIA), stroke, acute coronary syndrome or instable angina o New pulse loss o New vascular bruit o New anisotension
4. • Criterion 3 scores if at least one of the following biological inflammatory markers are elevated in the absence of any other reason: o Erythrocyte sedimentation rate at 1 hour > 30 mm/h ; o C-reactive protein > 10 mg/L ; o Fibrinogen > 4 g/L.
5. • Criterion 4 scores if at least one of the following radiological signs appears in a otherwise unaffected arterial territory: o New arterial wall thickening with wall contrast enhancement in vascular imaging Appearance of new vascular lesions (e.g., New arterial wall thickening stenosis, aneurysms) in Doppler, MRA, computed tomography angiography (CTA) or new hypermetabolism in 18-Fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG-PET).

Secondary endpoints 9

1. Cumulative incidence of relapse over the 12 months after initiation of experimental treatment
2. Cumulative incidence of treatment failure over the 12 months after initiation of experimental therapy
3. Cumulative prednisone dose over the 12 months after initiation of experimental treatment
4. Glucocorticoid-free disease remission will be assessed at 3, 6, and 12 months using the primary composite endpoint
5. Cumulative incidence of AE and SAE over the 12 months after initiation of investigational therapy
6. Change in the Physical Component Summary (PCS) of the SF36 between the start of experimental treatment,6 and 12 months after
7. Change in vascular lesions at 3, 6, and 12 months after the start of experimental treatment, measured by angio CT and/or magnetic resonance imaging angiography and/or Doppler
8. Change in vascular hypermetabolism at 6 and 12 months after the start of experimental treatment, measured by 18-FDG-PET
9. - Cumulative incidence of revascularization procedures (endovascular or surgical) required because of disease at 6 and 12 months after initiation of experimental therapy.

Investigational products

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

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

David SAADOUN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

David SAADOUN

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Results and documents

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

Documents 17 files

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

Application history

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