Immuno-modulation in Amyotrophic Lateral Sclerosis- a Phase II Study of Safety and Activity of Low Dose Interleukin-2
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- CD4+ CD25+ CD127- FoxP3+(Treg) cells: change in percentage of total lymphocytes
研究概览
简要总结
The primary objective is to evaluate in ALS patients the regulatory T cell early response to two low-doses of IL-2 at 1 and 2 MIU per day after one course of 5 consecutive days comparatively to placebo.
详细描述
This is a phase II study on ld-IL-2 as a therapeutic agent for ALS which aims at defining the activity and safety of a range a doses for subsequent use of the best dose in a phase II/III trial. For ethical reasons, ld-IL-2 must be tested as an add-on therapy to riluzole hence all patients will need to be treated with riluzole for at least three months prior to entry. A randomized (1:1:1), placebo-controlled, double-blind, parallel group trial will be carried out to assess ld-IL-2 activity on regulatory T cells and immuno-inflammatory markers in ALS patients treated for 3 months (5 days every four weeks repeated three times).
The secondary objectives of this study are:
A. To evaluate maintenance of Tcell response after three repeated 5-day courses at one course every four weeks for 12 weeks.
B. To evaluate the safety of ld-IL-2 therapy in an ALS population, with an overall follow-up of 6 months (up to 15 weeks after last administration); C. To evaluate functional changes throughout the study; D. To evaluate changes in other pre-defined blood cytology parameters, and a blood biomarker for axonal damage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient has been correctly informed
- •The patient must have given his/her informed and signed consent.
- •The patient must be insured or beneficiary of a health insurance plan.
- •The patient is at least 18 years old and less than 75 years old
- •Probable, or laboratory-supported probable or definite ALS as defined by El Escorial Revised ALS diagnostic criteria (according to Airlie House Conference 1988)
- •Stable on riluzole treatment for more than 3 months with liver function test results < 2ULN
- •Disease duration ≤ 5 years
- •Vital capacity ≥ 70% of normal
- •Ability to swallow without the requirement for nasogastric or PEG feeding
- •Agreement for patient to use an adequate method of contraception throughout the study and for 2 weeks after post study visit
- •The patient is available and willing to participate in seven study visits occurring at the CHU within the next six months
排除标准
- •The patient is participating in another interventional study
- •Within the past three months, the patient has participated in another interventional
- •The patient is in an exclusion period determined by a previous study
- •The patient is under judicial protection
- •The patient is an adult under guardianship
- •The patient refuses to sign the consent
- •It is impossible to correctly inform the patient
- •Other life threatening disease
- •Presence of contra-indicated concomitant treatments or with potential neuroprotective benefit (see section 11.2 of the protocol)
- •Presence of tracheostomy or non-invasive ventilation
- •Use of Percutaneous endoscopic gastrostomy (PEG) or nasogastric tube
- •Presence of clinical infection (treated or untreated)
- •Positive serology for CMV, EBV (confirmed by viral load), or HIV
- •Vaccination within 8 weeks prior to first experimental dosing
- •Other disease precluding functional assessments
- •Cancer within the past 5 years (except stable non-metastatic basal cell skin carcinoma or in situ carcinoma of the cervix)
- •Severe cardiac or pulmonary disease
- •Documented auto-immune disorders except asymptomatic Hashimoto thyroiditis
- •Women of child bearing age without contraception or pregnant or breast feeding
- •Any clinically significant laboratory abnormality (excepting cholesterol, triglyceride and glucose)
研究组 & 干预措施
Placebo
Patients in this arm will receive sub-cutaneous injections of placebo (same vehicle as for experimental arms, and same volume) for 5 consecutive days at the beginning of three consecutive months (a total of 15 injections, 5 per month for 3 months).
Intervention: Placebo
干预措施: Placebo (Drug)
1.0 IL-2
Patients in this arm will receive sub-cutaneous injections corresponding to 1.0 MIU of IL-2 per injection for 5 consecutive days at the beginning of three consecutive months (a total of 15 injections, 5 per month for 3 months).
Intervention: 1.0 MIU IL-2 per day
干预措施: 1.0 MIU IL-2 per day (Drug)
2.0 IL-2
Patients in this arm will receive sub-cutaneous injections corresponding to 2.0 MIU of IL-2 per injection for 5 consecutive days at the beginning of three consecutive months (a total of 15 injections, 5 per month for 3 months).
Intervention: 2.0 MIU IL-2 per day
干预措施: 2.0 MIU IL-2 per day (Drug)
结局指标
主要结局
CD4+ CD25+ CD127- FoxP3+(Treg) cells: change in percentage of total lymphocytes
时间窗: Day 8
Treg refers to regulatory T cells
次要结局
- Presence/absence of specific, pre-defined adverse events.(Day 64)
- Light chain neurofilament levels in serum(Week 13)
- MedDRA classification of all adverse events throughout the study(Week 25)
- Thyroid function: blood T4(Week 13)
- Thyroid function: blood TSH(Week 13)
- Presence/absence of clinically significant abnormality on a lung x-ray(Week 13)
- Presence/absence of abnormal vital signs(Week 25)
- Presence/absence of clinically significant abnormality on an electrocardiogram(Week 13)
- CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes(week 25)
- Presence/absence of a clinically significant abnormality among routine laboratory tests(Week 25)
- Vital capacity (% of normal)(Week 25)
- The ALSFRS Questionnaire(Week 25)
- Tregs (absolute number and % CF4+ cells)(Week 25)
- Total lymphocyte number(Week 25)
- Phosphorylated neurofilament heavy protein (pNfH) levels in serum(day 1)
- effector T cells: number and % of CD4 cells(Week 25)