A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Treatment Efficacy and Safety Study of MYOBLOC® in the Treatment of Adult Lower Limb Spasticity
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 18
- 主要终点
- The Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3]
研究概览
简要总结
Phase 2/3, randomized, double-blind, placebo-controlled, single-treatment, multicenter trial assessing the efficacy and safety of MYOBLOC for the treatment of lower limb spasticity, in adults followed by an open-label extension safety trial.
详细描述
Phase 2, randomized, double-blind, placebo-controlled, single-treatment, multicenter trial will compare the efficacy and safety of two doses of MYOBLOC (15,000 Units and 20,000 Units)versus volume-matched placebo in the treatment of lower limb spasticity in adults. An interim analysis will evaluate all available safety and efficacy data from the Phase 2 double-blind trial in order to recommend which dose will be evaluated in subsequent Phase 3 trial. The Phase 3, randomized, double-blind, placebo-controlled, single-treatment, multicenter trial will compare the efficacy and safety of MYOBLOC versus placebo in the treatment of lower limb spasticity in adults. Subjects who complete either the Phase 2 or Phase 3 trial will continue into an open-label extension part of the study where each will receive 4 separate treatments of MYOBLOC (20,000-25,000 Units) ~13 weeks apart for lower limb spasticity.
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)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand the potential risks and benefits, the study requirements, and provide written informed consent before enrollment into the study; or if unable, the subject's Legally Authorized Representative (LAR) may provide written informed consent.
- •Male or female ≥18 to maximum of 80 years of age, inclusive.
- •Lower limb spasticity due to stroke, traumatic brain injury, or spinal cord injury that occurred ≥6 months prior to randomization. Eligible subjects may have lower limb monoplegia or hemiplegia. Subjects with cerebral palsy are eligible for study enrollment.
- •Ambulatory (with or without the use of a walking assistive device).
- •Modified Ashworth Scale (MAS) score ≥2 in the ankle plantar flexors of the affected lower limb at screening and at baseline.
- •In the Investigator's opinion, the subject will be available and able to comply with the study requirements for at least 1 year, based on the subject's overall health and disease prognosis.
- •In the Investigator's opinion, the subject will be willing and able to comply with all requirements of the protocol, including completion of study questionnaires. A caregiver may be designated to assist with the physical completion of questionnaires/scales.
排除标准
- •Quadriplegia/tetraplegia, lower limb diplegia or triplegia.
- •Uncontrolled epilepsy or any type of seizure disorder with a seizure(s) within the previous year.
- •Neuromuscular disorders including, but not limited to, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), multiple sclerosis (MS), myasthenia gravis, or muscular dystrophy.
- •History of major joint contracture(s), in which, based on the Investigator's assessment, the contracture(s) significantly contribute(s) to joint immobility in the affected lower limb.
- •Unresolved fracture(s) in the affected lower limb.
- •Severe atrophy in the affected lower limb.
- •Known hypersensitivity to botulinum toxins type A or B or to any MYOBLOC solution components.
- •Concomitant use or exposure within 5 half-lives of randomization of the following: aminoglycoside antibiotics, curare-like agents, or other agents that may interfere with neuromuscular function.
- •Treatment with a neurolytic agent (e.g., phenol, alcohol blocks) to the affected lower limb within 1 year before randomization.
- •Presence of a spinal stimulator or intrathecal baclofen pump that has not been turned off within 30 days before screening.
- •Changes to treatment regimen or any new treatment with oral antispasmodics and/or muscle relaxants within 30 days before randomization.
- •Initiation of physical and/or occupational therapy <30 days before randomization. Subjects receiving physical and/or occupational therapy ≥30 days before randomization must be willing to maintain their therapy regimen through Week 4 of the DBP.
- •Application of an ankle-foot orthosis (AFO) <30 days before randomization. Subjects regularly using an AFO ≥30 days before randomization must be willing to maintain use of the AFO through Week 4 of the Double-Blind Period.
- •Prior botulinum toxin type A (BoNT/A) or B (BoNT/B) treatment in the affected lower limb within 24 weeks before screening. Prior BoNT/A or BoNT/B treatment in areas other than the affected lower limb is not exclusionary but must have occurred at least 12 weeks before screening. Prior toxin exposure must have been well tolerated and without any significant long-term side effects in the case of repeated prior exposure.
- •Subjects should not receive nor have any plans to receive any botulinum toxin treatment, other than the study drug (MYOBLOC), from the point informed consent is obtained until participation in the study is complete.
- •Severe dysphagia (i.e., inability to swallow liquids, solids or both without choking or medical intervention), or dysphagia with a history of aspiration pneumonia, within 6 months before screening.
- •Prior surgery to treat spasticity in the affected lower limb (i.e., tendon lengthening or tendon transfer).
- •Any anticipated or scheduled surgery during the study period, with the exception of dermatological procedures performed under local anesthesia for the purposes of removing precancerous and cancerous lesions.
- •Major surgery within 3 months before screening.
- •Pregnancy or breastfeeding.
- •Females of childbearing potential must agree to practice a medically acceptable method of contraception (e.g., intrauterine device, hormonal contraception started at least one full cycle before study enrollment or barrier method in conjunction with spermicide) for the duration of the study (including 2 months after study completion). For the purposes of this study, all females are considered to be of childbearing potential unless they are confirmed by the Investigator to be post-menopausal (at least 1 year since last menses and laboratory test confirmation), biologically sterile, or surgically sterile (e.g., hysterectomy with bilateral oophorectomy, tubal ligation).
- •History of drug or alcohol abuse within 6 months before screening.
- •Obstructive pulmonary disease with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <70%.
- •Slow vital capacity (SVC) <60% of predicted.
- •Chronic or current use of inhaled corticosteroids.
- •Ventilator dependence (i.e., 24-hour ventilator dependence when intubated, or due to a failure to wean the subject from the ventilator while hospitalized in the intensive care unit or respiratory care center). Subjects who use oxygen on an as-needed basis or during sleeping hours only via a nasal cannula are eligible for the study.
- •Infection at the planned sites of injection.
- •Treatment with an investigational drug, device, or biological agent within 30 days before screening or while participating in this study.
- •Malignancy diagnosed 3 months before screening.
- •Has one or more screening clinical laboratory test values outside the reference range that, in the opinion of the Investigator, are clinically significant, or any of the following :
- •Serum creatinine >1.5 times the upper limit of normal (ULN);
- •Serum total bilirubin > 1.5 times ULN;
- •Serum alanine aminotransferase or aspartate aminotransferase >2 times ULN.
- •Has any of the following cardiology findings at screening:
- •Abnormal ECG that is, in the Investigator's opinion/evaluation, clinically significant;
- •PR interval >220 ms;
- •QRS interval >130 ms;
- •QTcF interval >450 ms (for men), or >470 ms (for women) (QT corrected using Fridericia's method);
- •Second-or third-degree atrioventricular block;
- •Any rhythm, other than sinus rhythm, that is interpreted or assessed by the Investigator to be clinically significant.
- •Any other medical illness, condition, or clinical finding that, in the opinion of the Investigator and/or the Sponsor, would put the subject at undue risk.
研究组 & 干预措施
Phase 2; Placebo
Volume-matched placebo is a single treatment
干预措施: Phase 2; Placebo (Drug)
Phase 3; MYOBLOC
MYOBLOC is a single treatment and will be compared to volume-matched placebo
干预措施: Phase 3; MYOBLOC (Drug)
Phase 3; Placebo
Volume-matched placebo is a single treatment
干预措施: Phase 3; Placebo (Drug)
结局指标
主要结局
The Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3]
时间窗: Baseline and Week 4
The first co-primary endpoint is the change from baseline in the Modified Ashworth Scale (MAS) score in the tone of the ankle plantar flexors at Week 4 post-injection. The MAS is an internationally accepted and validated instrument used to measure resistance during passive soft-tissue stretching. Resistance will be measured and recorded using a 6-point scale ranging from 0 (no increase in muscle tone) to 4 (affected part\[s\] rigid in flexion or extension). A lower change from baseline MAS score (\<0) represents a better outcome.
The Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) in functional ability [Phase 2 and Phase 3]
时间窗: Week 4
The second co-primary endpoint is the Clinical Global Impression of Change (CGI-C) score in functional ability at Week 4 post-injection. The CGI-C scale is a single item clinician assessment of how much the patient's functional ability has improved, worsened or has not changed relative to the patient's baseline state prior to treatment (injection). The CGI-C is rated on a 7-point Likert scale from 1 to 7, where 1 = "Very much improved", 2 = "Much improved", 3 = "Minimally improved", 4 = "No change", 5 = "Minimally worse", 6 = "Much worse", and 7 = "Very much worse". Successful therapy is indicated by a lower score (\<4) in subsequent testing.
次要结局
- Effect of MYOBLOC on the Patient Global Impression of Change (PGI-C) [Phase 2 and Phase 3](Weeks 2, 8, 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Caregiver Global Impression of Change (GGI-C) [Phase 2 and Phase 3](Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Numeric Rating Scale of Pain (Pain-NRS) [Phase 2 and Phase 3](Baseline and Week 4)
- Effect of MYOBLOC on the Walking Impairment Questionnaire (WIQ) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on Walking and Resting Comfort Scale (WRCS) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on Modified Ashworth Scale (MAS) Responder Rate Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3](Baseline and Week 4)
- The Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- The Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) in functional ability [Phase 2 and Phase 3](Weeks 2, 8, and13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Clinical Global Impression of Severity (CGI-S) [Phase 2 and Phase 3](Baseline and Weeks 2, 4, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Patient Global Impression of Severity (PGI-S) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Caregiver Global Impression of Severity (GGI-S) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Pain Numeric Rating Scale (Pain-NRS) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))