A 52-Week Study Evaluating the Efficacy and Safety of Arumakimig (MAS825) in Participants With VEXAS Followed by Open-Label Extension (OLE) Period

Официальное название

VEX-AR: Randomized, Double-Blind, Placebo-Controlled, 52-Week Phase 2 Study Evaluating the Efficacy and Safety of Arumakimig (MAS825) in Participants With VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome, Followed by an Open-Label Extension Period

Обзор

The purpose of this study is to evaluate clinical efficacy and safety of arumakimig (MAS825) compared to placebo in patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome. In addition, the study will evaluate the long-term efficacy, safety and tolerability of arumakimig in this population.

Подробное описание

This is a randomized, double-blind, placebo-controlled study with a 52-week duration evaluating the efficacy and safety of arumakimig in participants with VEXAS who are receiving glucocorticoids. Participants will be randomized 1:1 to either arumakimig or placebo.

Following the double-blind period, participants may have the option to enter a 2-year (104-week) open-label extension (OLE) period, continuing until Week 156.

A 16-week safety follow-up period must be completed after the OLE (up to Week 172) or after the double-blind period (up to Week 68).

Вмешательства

• Препарат Arumakimig
  Arumakimig Injection
• Препарат Placebo
  Placebo Injection
• Препарат Oral glucocorticoids
  Background therapy with glucocorticoids. After the first 2 weeks of the study, participants may begin with glucocorticoid tapering depending on the disease status and the Investigator's judgement.

Первичные конечные точки

• Number of participants achieving improvement of key VEXAS manifestations and oral glucocorticoid (GC) reduction at Week 52 [Срок оценки: From baseline up to Week 52]

Вторичные конечные точки (9)

• Number of participants achieving Overall Clinical Response (OCR) at Week 52 [Срок оценки: From baseline up to Week 52]
• Number of participants achieving resolution of VEXAS manifestations [Срок оценки: From baseline up to Week 52]
• Number of participants with oral glucocorticoid reduction [Срок оценки: From baseline up to Week 52]
• Total number of flare-free days over 52 weeks [Срок оценки: Up to 52 weeks]
• Number of participants achieving Hematologic Improvement - Erythroid (HI-E) during the double-blind treatment period [Срок оценки: From baseline up to Week 52]
• Number of participants achieving Hematologic Improvement - Platelets (HI-P) during the double-blind treatment period [Срок оценки: From baseline up to Week 52]
• Number of participants without worsening disease according to a participant-reported questionnaire [Срок оценки: From baseline up to Week 52]
• Time to death during the double-blind treatment period [Срок оценки: Up to 52 weeks]
• Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: Up to 172 weeks]

Критерии участия

Критерии включения

• Male and female participants aged ≥18 years at screening.
• Somatic mutation in UBA1 gene known to be associated with VEXAS.
• Participants must have at least two manifestations of VEXAS at screening or in the past 6 months.
• Participants must be able to start treatment for Pneumocystis jiroveci pneumonia (PJP) during the study if indicated according to the local guidelines.
• Ability to communicate well with the Investigator, understand and agree to comply with the requirements of the study.

Критерии исключения

• Participants meeting any of the following criteria are not eligible for this study:
• Positive serology for hepatitis B surface antigen (HBsAg) excludes the participant.

HBsAg negative participants who are hepatitis B core antibody (HBcAb) positive are also excluded unless protocol-defined criteria are met.

• Participants with a positive HCV antibody test should have HCV ribonucleic acid (RNA) levels measured. Participants with positive (detectable) HCV RNA must be excluded. Chronic hepatitis C patients who have completed HCV anti-viral treatment must be HCV-RNA negative at least 12 weeks after treatment before randomization to be eligible.
• Active viral, bacterial, or other infections requiring systemic treatment at the time of screening or randomization, or history of recurrent clinically significant infection or of recurrent bacterial infections.
• Known or suspected Human Immunodeficiency Virus (HIV) infection. Should it be required by local regulations and/or considered appropriate by the Investigator, an HIV test can be performed locally to confirm eligibility.
• Live vaccinations within a certain period prior to arumakimig treatment. Live vaccines are prohibited during the trial and up to a certain period following the last dose of arumakimig.
• History of malignancy of any organ system, including post-transplant lymphoproliferative disorder (except for skin Bowen's disease, completely treated and resolved, localized squamous or basal cell carcinoma of the skin or actinic keratosis that have been treated with no evidence of recurrence in the past 12 weeks, in situ cervical cancer or non-invasive malignant colon polyps that have been removed), treated or untreated, within a protocol-defined period, regardless of whether there is evidence of local recurrence or metastases.
• History of or current hepatic disease (moderate to severe Hepatic Impairment as per Child-Pugh classification), including but not limited to, acute or chronic hepatitis (for Hepatitis B or C), cirrhosis or hepatic failure.
• Participants of child-bearing potential who do not agree to comply with required contraceptive use as outlined in the protocol.

Other protocol-defined inclusion/exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07748624 · CMAS825G12203 · 2026-527354-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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