A Phase 1 Study to Determine the Safety and Tolerability of Continuous Intrathecal Riluzole in Patients With Progressive Ambulatory Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal neurological exam findings
研究概览
简要总结
The purpose of this study is to investigate the safety and tolerability of intrathecal riluzole in adults with amyotrophic lateral sclerosis.
详细描述
ALS/MND is a progressive motor neurone disease. Oral riluzole is approved for the treatment of ALS/MND in Australia as well as other countries. Unfortunately, in pill form, the drug's efficacy is limited by erratic absorption from the gut, dosing is limited by liver toxicity, and patients often experience brain fog as a troubling side effect. Evidence from dogs suggests that receiving the same drug through an implanted pump that infuses it directly into the cerebrospinal fluid around the cells that support breathing, allows these cells to get 3 to 10 times as much riluzole , and guarantees that it is always there at the desired amount. In addition, this delivery approach should not contribute to increased brain fog.
Patients who have demonstrated the ability to tolerate oral riluzole will have a SynchroMed® II Infusion Pump and Ascenda ® Intrathecal Catheter implanted. Once deemed medically appropriate, 6-weeks of continuous IT riluzole will be administered. Safety and tolerability will be assessed by a safety committee for the first 3 participants enrolled. With Safety Committee approval, these participants will continue on 6-months of treatment and a further 7 participants will be enrolled for a total of 32 weeks treatment.
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
盲法说明
Open Label
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
- •Men and women aged 18 years or older.
- •Participants are ambulatory with or without an assistive device.
- •Sporadic or familial ALS diagnosis with possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
- •Slow vital capacity (SVC) measure ≥70% of predicted for gender, height, and age.
- •Medically able to undergo implantation of the SynchroMed II Infusion Pump according to the judgment of the investigator, or the presence of a previously implanted IT pump (not to be used for concurrent IT infusion of another IT agent).
- •Capable of reading and providing informed consent and following study procedures.
- •Geographic accessibility to the study center and the ability to travel to the clinic for study visits by ground transportation.
- •Women must not be able to become pregnant (eg, post menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and 3 months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal (patch or contraceptive ring, for example) contraception), intrauterine device in place for ≥3 months, barrier method in conjunction with spermicide, or another adequate method.
- •Taking and tolerating oral riluzole 50 mg twice a day for at least 30 days prior screening and willingness to continue oral riluzole throughout duration of the study.
- •Patients may take other drugs approved for treatment of ALS at the dose prescribed by their neurologist.
排除标准
- •Participants with bulbar-onset ALS
- •Participants at risk of increased bleeding or uncontrolled bleeding during the SynchroMed II Infusion Pump implantation or following explant. This includes but is not limited to:
- •Anatomical factors at or near the site of implantation;
- •Underlying disorders of the coagulation cascade or platelet function (eg, hemophilia, Von Willebrand's disease, liver disease);
- •Administration of antiplatelet or anticoagulant medication within 7 days before or after pump implantation (eg, aspirin, clopidogrel bisulfate, rivaroxaban, nonsteroidal anti-inflammatory agents [NSAIDs]), or
- •Use of nutritional supplements (eg, St John's Wort) within 7 days before or after pump implantation.
- •Presence of infection including but not limited to: meningitis, ventriculitis, skin infection, bacteremia, or septicemia.
- •Testing positive for HIV (anti-HIV antibody), HBV (HBV surface antigen) or HCV (anti-HCV antibody; HCV RNA if anti-HCV antibody is positive) at screening.
- •Inability to have the infusion pump implanted ≤ 2.5 cm below the skin surface.
- •Body weight and size unable to accept the infusion pump bulk and weight.
- •Spinal anomalies which would complicate the implantation and fixation of the catheter for IP delivery.
- •Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) value > 2.0 times the upper normal.
- •A life expectancy of less than 6 months, based on the judgment of the investigator.
- •Presence of tracheostomy.
- •The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair the ability of the participant to provide informed consent, per investigator judgment.
- •History of active substance abuse within the prior year.
- •At risk for committing suicide per investigator judgment.
- •Clinically significant history of unstable or severe cardiac, oncologic, hepatic, or renal disease, or other medically significant illness.
- •Pregnant women or women currently breastfeeding.
- •Exposure to any investigational drug, device, or biologic within 30 days of screening.
研究组 & 干预措施
Single Arm
Intrathecal riluzole continuous infusion up to 0.2 mg / hr.
干预措施: Intrathecal Riluzole (Drug)
结局指标
主要结局
Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal neurological exam findings
时间窗: 6 weeks
Serial assessment all adverse events, neurological examination
Safety and tolerability of 0.2mg/hr intrathecal, infusion of intrathecal riluzole, Number of participants with with abnormal laboratory tests results
时间窗: 6 weeks
Serial assessment all abnormal findings in clinical laboratory test results
Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal vital signs
时间窗: 6 weeks
Serial assessment of adverse events, vital signs (blood pressure, pulse, respiratory rate and temp)
Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with with abnormal physical examination findings
时间窗: 6 weeks
Serial assessment of abnormal findings in a neurological examination for ALS patients
Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal findings in the Neuropathic Pain Scale (NPS)
时间窗: 6 weeks
Serial assessment all abnormal findings in the Neuropathic Pain Scale (NPS)
Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with adverse events, Columbia-Suicide Severity Rating Scale (C-SSRS).
时间窗: 6 weeks
Serial assessment all adverse events in the Columbia-Suicide Severity Rating Scale (C-SSRS).
次要结局
- Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal vital signs(6 months)
- Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal physical examination findings(6 months)
- Safety and tolerability of 0.2mg/hr intrathecal, infusion of intrathecal riluzole, Number of participants with with abnormal laboratory tests results(6 months)
- Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal neurological exam findings(6 months)
- Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with abnormal findings in the Neuropathic Pain Scale (NPS)(6 months)
- Safety and tolerability of 0.2mg/hr intrathecal infusion of intrathecal riluzole, Number of participants with adverse events, Columbia-Suicide Severity Rating Scale (C-SSRS).(6 months)