Phase II Study Evaluating the Efficacy and Safety of Secukinumab versus Combination Therapy in Patients with Active Severe Takayasu Arteritis

The primary objective is to evaluate disease remission, defined as an NIH score ≤ 1 at 6 months, in patients with severe Takayasu arteritis following the discontinuation of prednisone. The secondary objectives include:

• Assessment of the incidence of relapse and treatment failure, based on NIH criteria ≥ 2.
• Evaluation of the cumulative dose of prednisone and the rate of glucocorticoid-free remission at 3, 6, and 12 months.
• Monitoring of adverse events and serious adverse events.
• Measurement of the impact on quality of life at 6 and 12 months.
• Evaluation of vascular lesions and vascular hypermetabolism via 18-FDG-PET at 3, 6, and 12 months.
• Determination of the incidence of revascularization procedures, including endovascular or surgical interventions, at 6 and 12 months.

The sponsor did not provide information regarding the total number of participants. The study population consists of individuals diagnosed with Takayasu arteritis. Eligible participants include both male and female subjects within specific age ranges. The inclusion criteria require a diagnosis based on the American College of Rheumatology/EULAR or Ishikawa criteria modified by Sharma. The study focuses on patients with severe Takayasu arteritis, characterized by refractory or relapsing disease or significant arterial involvement. Participants must have had active disease, defined by a National Institutes of Health score greater than 1 within the previous two months. Individuals must be able to receive a stable dose of prednisone or an equivalent corticosteroid. Exclusion criteria include the presence of chronic active infections, although patients with a positive tuberculosis test may be included if active disease is ruled out. Necessary precautions include the use of effective contraception and negative pregnancy tests for women of childbearing age.

This phase II, prospective, Bayesian, randomized, open-label, parallel-group, controlled study is designed to evaluate the efficacy and safety of secukinumab compared to standard of care in patients with active severe Takayasu arteritis. The research methodology involves comparing the test product against several comparator therapies, including infliximab, tocilizumab, and adalimumab. Following a screening visit to assess eligibility based on National Institutes of Health scores and clinical criteria, participants are assigned to a treatment group. The study evaluates disease remission, defined by an NIH score ≤ 1 and the discontinuation of prednisone, as the primary endpoint at 6 months. Participants undergo multiple follow-up assessments at 3, 6, and 12 months to monitor glucocorticoid-free remission, relapse incidence, treatment failure, and changes in vascular lesions via imaging modalities such as magnetic resonance imaging angiography or computed tomography angiography. The total duration of participant involvement extends up to 12 months after the initiation of the experimental treatment. The study concludes with an end-of-study evaluation of cumulative adverse events and changes in health-related quality of life.

The experimental treatment consists of secukinumab, provided as a 300 mg solution for injection in a pre-filled pen. This medication is administered via subcutaneous injection.

Comparator treatments include infliximab, which is administered at a dose of 5 mg/kg through intravenous administration. Tocilizumab is also utilized as a comparator and is available for intravenous, subcutaneous, or intramuscular administration. Additionally, adalimumab is used as a comparator treatment, administered at a dose of 40 mg via subcutaneous use.

The primary efficacy endpoint is disease remission, defined as achieving a National Institutes of Health (NIH) score of ≤ 1 at 6 months in conjunction with the discontinuation of prednisone. Disease activity is quantified using the NIH criteria, which evaluate four clinical categories on a scale of 0 to 4 points. A score of 2 or higher indicates active disease. The assessment components include:

• Constitutional symptoms or extra-vascular manifestations.
• New clinical signs, such as carotidodynia, vascular claudication, transient ischemic attack, stroke, pulse loss, vascular bruit, or anisotension.
• Elevated biological inflammatory markers, specifically erythrocyte sedimentation rate, C-reactive protein, or fibrinogen.
• New radiological signs, including arterial wall thickening, vascular lesions identified via Doppler, magnetic resonance angiography, or computed tomography angiography, or new hypermetabolism on 18-Fluorodeoxyglucose positron emission tomography/computed tomography.

Secondary efficacy parameters involve the cumulative incidence of relapse and treatment failure over 12 months, as well as the cumulative prednisone dose during this period. Glucocorticoid-free remission is evaluated at 3, 6, and 12 months. Additional assessments include the change in the Physical Component Summary of the SF36 at 6 and 12 months. Changes in vascular lesions are measured at 3, 6, and 12 months using angio CT, magnetic resonance angiography, or Doppler. Vascular hypermetabolism is monitored at 6 and 12 months via 18-FDG-PET. Furthermore, the cumulative incidence of revascularization procedures is assessed at 6 and 12 months.