Phase II Interventional Study Evaluating Efficacy and Safety of Secukinumab in Active Severe Takayasu Patients

Conditions

• Large Vessel Vasculitis
• Takayasu Arteritis

Eligibility Criteria

Sex

ALL

Age

15 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Secukinumab — DRUG
  300 mg subcutaneous Secukinumab at Week 0, 1, 2, 3, 4 and then every 4 weeks until W24 (10 administrations)
• Standard of Care (SOC) — OTHER
  i.e., TNF inhibitors or tocilizumab, at physician's discretion, according to the French, European and international recommendations

Study Details

Takayasu's arteritis (TAK) is a large vessel vasculitis preferentially affecting the aorta and its main branches, leading to wall vessels thickening, fibrosis, stenosis, and occlusion. Patients with TAK have a high morbidity rate, 50% will relapse and experience a vascular complication within 10 years from diagnosis. TAK inflammation is mediated by T cells and macrophages. Pro-inflammatory Th1 and Th17 cells are dominant infiltrates in the vascular walls, producing IFN-γ and IL-17 to drive the systemic and vascular manifestations of TAK. Currently, TAK patients are principally treated with non-specific steroids, which are associated with potential side effects, especially when used for a long-time course. Steroid treatment preferentially target innate cytokines, such as IL-1β, IL-12, and IL-6 but have little effect on tissue-residing T cells. Novel approach needs to eliminate all T-cell effectors. The use of classical immunosuppressive drugs (IS) (methotrexate, Leflunomide) and biotherapies are prescribed earlier in the management of the disease in order to improve remission, spare corticosteroids and reduce relapses. Data from observational series report remission in 37-76% of cases with anti TNF alpha and 68% with Tocilizumab. However, a placebo-controlled trial failed to show superiority of tocilizumab in TAK. To date, no immunomodulatory treatment has been approved for the management of TAK and corticosteroids sparing remains a major challenge in this disease. Our team has demonstrated the key role of Th1 and Th17 responses in the pathophysiology of TAK. We found that Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK and glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK. Other teams further confirmed the significant increase in Th17 axis in TAK, and its correlation with disease activity, clinical relapse and arterial fibrosis. Secukinumab is a fully human monoclonal antibody that selectively inhibits IL-17A. Secukinumab received approval for adult treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, active non-radiographic axial spondyloarthritis, and active ankylosing spondylitis in numerous countries, including the EU and the USA Recently, a phase II clinical trial assessing the efficacy and safety of secukinumab vs placebo in combination with glucocorticoid taper regimen in giant cell arteritis showed that patients with active giant cell arteritis had a higher sustained remission rate in the secukinumab group than in the placebo group at week 28, and is now being studied in a phase 3 study (NCT04930094).Secukinumab was well tolerated with no new safety concerns. In TAK, recent observational data suggested that secukinumab might be an effective alternative to TNFi in severe TAK patients. Inhibition of IL-17A could represent a potential new therapeutic option for the treatment of severe TAK disease, hence the need for a prospective study to evaluate secukinumab in the management of active severe TAK.

Key Dates

Start date

Apr 1, 2026

Status verified

Mar 2026

Primary completion

Oct 1, 2029

Completion

Apr 1, 2030

Study Design

Enrollment

52 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: secukinumab
• Active Comparator: Standard of care

Primary Outcome Measure

Disease remission [ Time Frame: At 6 months ]

Central Contacts

• David Saadoun, MD PhD
  +33 1 42 17 80 42
  [email protected]
• Jérôme Lambert, MD PhD
  0142499742
  [email protected]

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  Recruiting · University of Pennsylvania · Boston, Massachusetts