A Double Blind, Randomized, Placebo Controlled Phase 2b Study to Evaluate the Safety and Clinical Efficacy of Treatment With the Autologous Cell Therapy Product, NG01, in Patients With Secondary Progressive Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Walking Ability
研究概览
简要总结
The goal of this clinical trial is to assess the safety and efficacy of repeated intrathecal (IT) injection of NG01, autologous bone marrow derived human stromal cells, in treating Secondary Progressive Multiple Sclerosis (SPMS), compared to placebo.
The study will assess the proportion of participants demonstrating improvement in walking ability, defined as a reduction in the average time to complete the Timed 25-Foot Walk (T25FW) at 6, 9, and 12 months compared to baseline. This will be analyzed by the mean change in walking speed across these time points. The study will also evaluate the incidence and nature of treatment-emergent adverse events (AEs).
Participants will receive intrathecal administrations of NG01, by lumbar puncture, and will be followed up for 6 months after their fourth administration.
详细描述
This is a multi-center, international Phase 2b, dose finding, randomized, double-blinded, placebo-controlled, three arm study, designed to assess the safety and efficacy of 4 IT administrations of NG01, compared to placebo, with a 4-month run-in period followed by a period of 9 months treatment with 6 months of follow-up, in patients with SPMS. Participants will continue to receive their customary MS treatment regimen at a stable dose.
The study will enroll 45 participants with secondary progressive multiple sclerosis (SPMS), randomized in a 1:1:1 ratio, to receive four intrathecal administrations-3 months apart over a 9-month period-of either high-dose NG01, low-dose NG01, or placebo. All participants will undergo clinical and safety assessments throughout the 9-month treatment period.
Upon completion of the 9-month treatment period, double-blind treatment and assessment period, participants will be followed clinically for an additional 6 months. The primary clinical outcome assessment and magnetic resonance imaging (MRI) acquisition for imaging assessments will occur post-treatment initiation (baseline).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
CRO Monitors, Sponsor
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants aged 18 to 65 years old.
- •Diagnosis of SPMS.
- •Documented EDSS worsening over the 2 years prior to study entry of ≥1 point for participants with EDSS <6.0 at screening, and ≥0.5 point for participants with EDSS ≥6.0 at screening, or a documented worsening of at least 20% in the T25FW. If documented T25fW or EDSS is not available, a written summary of the clinical evidence of disability worsening over the previous 2 years and retrospective assessment of EDSS score from data up to 2 years prior to screening, must be submitted for central review by adjudication committee.
- •EDSS at the screening visit from 3.5 to 6.5 at screening.
- •T25FW at the screening visit of from 8.0 to 25 seconds.
排除标准
- •Documented clinical relapse during the 24 months prior to enrollment and/or evidence of enhancing lesions on an MRI obtained at screening.
- •Pregnancy, breast feeding or women with childbearing potential without an acceptable form of contraception.
- •History of a general chronic handicapping/incapacitating disease other than MS.
- •Participants with clotting disorders
- •Participants unable to undergo an MRI scan.
- •Participants with uncontrolled hepatic disorders, renal or cardiovascular disease, or cancer.
- •Laboratory tests out of normal ranges considered by the investigator as clinically significant.
- •Participants with history or current alcohol abuse or drug addiction.
- •Untreated or uncontrolled psychiatric disorders, or positive suicidal risk assessed by Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Participation in another research study involving an investigational product (IP) in the 90 days prior to inclusion, or planned use of another IP during the study duration.
- •Participants who have ever received NG01/MSCs treatment.
- •Participants who, in the opinion of the investigator, are unable to fully comprehend the consenting process or likely to be non-compliant with the study procedures or for whom long-term follow-up seems difficult to achieve.
- •Relapse occurring between screening and randomization.
- •Less than 6 months of the current disease-modifying therapy
研究组 & 干预措施
100x10^6 cells
15 participants with SPMS will receive 4 IT administrations of NG01 (100×10^6 cells), 3 months apart
干预措施: NG01 - Autologous bone marrow derived human stromal cells (Biological)
50x10^6 cells
15 participants with SPMS will receive 4 IT administrations of NG01 (50×10^6 cells), 3 months apart
干预措施: NG01 - Autologous bone marrow derived human stromal cells (Biological)
Placebo
15 participants with SPMS will receive 4 IT administrations of placebo solution, 3 months apart
干预措施: Sodium Chloride 0.9% (Other)
结局指标
主要结局
Walking Ability
时间窗: 12 months
Proportion of participants who achieved improvement in walking ability over baseline by mean change in walking speed based on the Timed 25-Foot Walk (T25FW) test, averaged over visits at month-6, month-9 and month-12. Baseline is defined as the change in average timed walk compared to baseline (average timed walk at 6-, 9-, 12-months minus baseline \< 0)
Incidence of Treatment-Emergent Adverse Events (AEs)
时间窗: 15 months
The occurrence of treatment-related AEs will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 following enrollment, NG01 or placebo administrations (intrathecal), and during the 6 months of follow-up.
次要结局
- Walking Speed(12 months)
- Neuroimaging Parameters - Change in T2-hyperintense Lesion(12 months)
- Neuroimaging Parameters - Change in T1-hypointense Lesion(12 months)
- Neuroimaging Parameters - Change in Brain and Thalamus(12 months)
- Efficacy - Finger Dexterity(12 months)
- Quality of Life (QoL)(12 months)
- Fatigue(12 months)
- Walking ability(12 months)
- Efficacy - Congnition(12 months)
- Change in Disability(12 months)