Study of the Efficacy and Safety of a Bispecific Antibody, Teclistamab in Severe Rapidly Progressive Interstitial Lung Disease Associated With Anti-MDA5.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 24
- 主要终点
- The primary objective is to demonstrate the efficacy of teclistamab in improving transplant-free survival of patients with anti-Melanoma differentiation-associated protein 5 associated rapidly progressive diffuse interstitial lung disease.
研究概览
简要总结
Patients with severe, rapidly progressive diffuse interstitial lung disease (RP ILD) with anti-MDA5 have an appalling prognosis and the lack of effective medical treatment leads to lung transplantation being proposed as salvage treatment. Currently, transplant-free survival at 90 days (D90) is approximately 25%, dropping to less to 10% among those requiring mechanical ventilation. Peripheral lymphopenia and elevated anti-MDA5 antibody levels are associated with greater disease severity, highlighting the involvement of mature T and B lymphocytes in disease pathogenesis.
Teclistamab, a bispecific antibody targeting the B-cell maturation antigen (BCMA) on plasma cells and engaging T cells - approved for the treatment of refractory multiple myeloma - has recently shown rapid and promising effects in patients with autoimmune conditions, including one MDA5-positive patient, while maintaining a favourable safety profile. We hypothesize that this bispecific antibody could represent a promising and safe therapeutic option for patients with severe MDA5-associated RP-ILD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient ≥ 18 years old
- •MDA5 antibody positivity
- •ILD confirmed by chest HRCT
- •Within less than 3 months after disease onset
- •Refractory after more than 7 days to high dose steroids and two immunosuppressants drugs as first-line treatment.
- •Confirmation of refractoriness by the national emergency multidisciplinary discussion (MDD),
- •Worsening of respiratory symptoms with respiratory distress defined by increase in oxygen supply to reach SpO2>95% or requirement of mechanical ventilation
- •Written informed consent obtained from the patient or the trusted support person designated in advance by the patient
- •Patients covered by the French social security system
- •Effective contraception for woman of childbearing age during treatment and for five months after the last dose of teclistamab.
- •Effective contraception for men, having a partner of childbearing age, during treatment and for three months after the last dose of teclistamab.
排除标准
- •Patient with known hypersensitivity to teclistamab, substance active or excipients, including sodium or polysorbate
- •Patient or the trusted person designed by the patient not able to give their consent
- •Known diagnosis of a serious comorbidity: active cancer, malignant blood disease, ongoing infection, stroke or seizure within 6 months
- •Patient who received a live vaccine within 4 weeks prior to study inclusion.
- •Patient under judicial protection, deprivation of liberty
- •Patient participating in another clinical trial with an investigational medicinal product
- •Pregnant or breastfeeding woman
- •Patient on AME (state medical aid)
研究组 & 干预措施
Experimental
Dosage and subcutaneous administration of Teclistamab:
Day 1: 0.06 mg/kg Day 3: 0.3 mg/kg Day 5: 1.5 mg/kg)
干预措施: Teclistamab(SC) (Drug)
结局指标
主要结局
The primary objective is to demonstrate the efficacy of teclistamab in improving transplant-free survival of patients with anti-Melanoma differentiation-associated protein 5 associated rapidly progressive diffuse interstitial lung disease.
时间窗: at 90 days
The primary endpoint is transplant-free survival at 90 days, defined as the time from inclusion to lung transplantation or death from any cause.
次要结局
- To assess the length of stay in hospital(at 90 days)
- To evaluate disease severity(at 90 days)
- To evaluate the response of Interstitial Lung Disease on imaging(From enrollment to the end at week 24)
- To assess the tolerance profile of teclistamab(to day 1 of treatment to the end of treatment (4 week ))
- To evaluate the response of extra-respiratory manifestations including muscular involvement(From Day 0 at week 24)
- To evaluate overall survival(from inclusion to day 90)