A Phase I Trial to Evaluate Safety and Tolerability of Abatacept Followed by Subcutaneous Interleukin-2 Administration in Patients With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- To evaluate adverse events and laboratory abnormalities to assess the safety and tolerability of abatacept followed by Interleukin 2 (IL-2) administration in ALS patients
研究概览
简要总结
In Amyotrophic Lateral Sclerosis (ALS), the reduction of regulatory T-lymphocyte (Treg) numbers and suppressive function correlates with rapid disease progression. The investigator completed a phase 1 study of infusions of expanded autologous Tregs in combination with subcutaneous IL-2 injections in ALS patients, which showed enhancement of Treg numbers and suppressive function in vivo. The enhanced Treg suppressive function correlated strongly with slowing and stabilization of disease progression. Drugs that enhance endogenous Treg numbers and suppressive function may also stabilize disease in ALS. This phase 1 study aims to determine whether the combination therapy of subcutaneous IL-2 and abatacept (Orencia®) is safe and well-tolerated in 6 patients with ALS, and whether the therapy enhances Treg numbers and suppressive function in vivo.
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
- •Patients will be eligible for initial enrollment on this study if they meet the following criteria at the time of screening:
- •Provided informed consent and authorized use of protected health information (PHI) in accordance with national and local patient privacy regulations.
- •ALS meeting El Escorial criteria for possible, probable, lab-supported probable, or definite ALS.
- •At least 18 years old.
- •Total bilirubin less than or equal to 1.5 mg/dL
- •Alanine aminotransferase level (ALT) less than or equal to five times normal, albumin greater than or equal to 3.0 gm/dL
- •Serum creatinine less than 1.5 mg/dL
- •Capable of complying with all study procedures, including the study drug delivery procedure, in the Investigator's opinion.
- •A family member or caretaker who is expected to be consistently available to administer both study drugs of abatacept and IL-2 if the participant is unable to do so.
- •On a stable regimen of riluzole for at least 30 days at the time of screening. If not on riluzole at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
- •Patients on edaravone willing to refrain from taking edaravone on the same day as they will receive the abatacept injection for the duration of the trial. If not on edaravone at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
- •Forced vital capacity (FVC) ≥50% of predicted capacity for age, height, and sex at screening, or receiving treatment with noninvasive ventilation if FVC < 50% of predicted for age, height, and sex at screening.
排除标准
- •Patients will be ineligible to participate if any of the following are true at the time of screening:
- •Serious, active bacterial, fungal, or viral infection, active or latent tuberculosis.
- •Tracheostomy.
- •Severe cardiac dysfunction defined as left ventricular ejection fraction <40% if an echocardiogram is medically indicated to clarify ongoing symptoms or EKG findings.; a history of non-controlled cardiac arrhythmias; history of cardiac tamponade; Unstable angina or MI in the last 3 months.
- •Hypersensitivity or allergy to IL-2 or abatacept.
- •History of bowel ischemia/perforation, or GI bleeding requiring surgery.
- •History of resistant seizures, history of coma or toxic psychosis lasting >48 hours.
- •Platelets <100,000/mm3; hematocrit <30%.
- •History of cancer in the past 5 years (except cutaneous Basal cell carcinoma or squamous cell carcinoma).
- •Hx of immunomodulation therapy including IL-2 or abatacept administration in the past 90 days.
- •Treatment with another investigational drug, biological agent, or device within 30 days or 5 half-lives of screening, whichever is longer.
- •If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or unwilling to use effective contraception for the duration of the trial and for 90 days after treatment.
- •If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 90 days after treatment
研究组 & 干预措施
Phase I Study in ALS with Abatacept & IL-2
Primary Objective:
1. To assess the safety and the tolerability of abatacept followed by IL-2 administration in ALS patients
Secondary Objectives:
- To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring the change in the number of Tregs
- To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring the change in the suppressive activity of Tregs on T effector proliferation.
- To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring in the level of cytokines secreted by PBMCs throughout the course of the study
Exploratory Objective:
1. To characterize the effects of abatacept followed by IL-2 on clinical outcome measures of ALS, including the Appel ALS Rating Scale (AALS) and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, and the forced vital capacity (FVC) and maximum inspiratory pressure (MIP).
干预措施: Abatacept Injection [Orencia] and Proleukin (aldesleukin) (Drug)
结局指标
主要结局
To evaluate adverse events and laboratory abnormalities to assess the safety and tolerability of abatacept followed by Interleukin 2 (IL-2) administration in ALS patients
时间窗: 24 months
Incidence and severity of AEs, including changes in laboratory values and vital signs. The investigator will determine whether safety and tolerability of abatacept followed by IL-2 administration are acceptable in order to proceed with the next phase. Safety and tolerability will be assessed throughout the study.
次要结局
- Change in Regulatory T cells (Tregs) numbers in the blood from baseline(Baseline to Week 15)
- Change in Regulatory T cells (Tregs) suppressive function in the blood from baseline(Baseline to Week 15)
- Changes in the level of cytokines secreted by PBMCs from baseline(Baseline to Week 15)