First in Human Study to Evaluate Safety of Cellavita HD Investigational Product After Intravenous Application in Participants With Huntington's Disease
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Safety of Cellavita HD by periodic monitoring changes at adverse events, vital signs, laboratory tests, ECG and incidence of benign and malignant neoplasms
研究概览
简要总结
Cellavita HD is a stem-cell therapy for Huntington's Disease. This is a first-in-human, non-randomized, phase I study in which participants with Huntington's Disease will receive three intravenous injections and will be followed for 5 years to evaluate safety and tolearability of product and preliminary evidence of effectiveness.
详细描述
This is a first-in-human, non-randomized, phase I study in which participants with HD will receive three intravenous injections of one of two doses of the investigational product, one every month for three months. Safety evaluation data will be composed by the register of adverse events (including type, frequency, intensity, seriousness, severity, and action taken related to the investigational product), could be include changes in vital signs, physical and medical evaluations, laboratory or serology tests and electrocardiogram (ECG), and by the incidence of benign and malign neoplasms. Preliminary evidence of efficacy will be evaluated by global clinical improvement (CIBIS) and evolution of disease improvement (motor, cognitive and behavioral degradation) through Unified Huntington's Disease Rating Scale - UHDRS and inflammatory markers: IL-4, IL-6, IL-10 (interleukin IL) e TNF-alpha (tumoral necrosis factor alpha). CNS improvement will be assessed by magnetic resonance imaging (MRI). Fluctuation in suicide tendency grade will be evaluated by Hamilton Depression Rating Scale (HDRS).The immunological response of HD product over the administration period will be evaluated by CD4+ and CD8+ proliferation and inflammatory markers release.
Participants who show evidence of loss of clinical benefit achieved over the course of treatment verified through worsening greater or equal to that expected for the natural course of the disease on motor, cognitive, behavioral and functional capacity symptoms assessed by the UHDRS scale, will receive additional doses of the product as long as there is clinical benefit at the Investigator's discretion and/or until the product is marketed. The same dose used by the subject during the treatment period will be administered throughout the period of additional doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Sign and date ICF;
- •Ability to follow instructions as well as ability to understand and fulfill the study requirements correctly;
- •Male participant aged ≥ 21 and ≤ 65;
- •Participants who submit medical report (PCR) attesting Huntington's disease with a number of CAG repeats on chromosome 4, greater than or equal to 40 and less than or equal to 50 (if the participant has not performed the examination and/or if he does not have the report available, a new exam should be done);
- •Score 5 points or more in motor assessment UHDRS scale (Unified Huntington's Disease Rating Scale) at the time of enrollment;
- •Score between 8 and 11 points in the functional capacity of the UHDRS scale at the time of enrollment.
排除标准
- •Participation within 12 months in any clinical trial;
- •Any medical observation data (clinical and physical) that medical research judge as a risk for subject if enrollment at the study;
- •Any laboratory exam data that medical research judge as a risk for subject if enrollment at the study;
- •Juvenile Huntington disease diagnosis;
- •History of epilepsy;
- •Diagnostic of major cognitive impairment;
- •Active decompensated psychiatric disease;
- •Current or prior history of neoplasia;
- •Current history of gastrointestinal, hepatic, renal, endocrine, pulmonary, hematologic, immune, metabolic pathology or severe and uncontrolled cardiovascular disease;
- •Diagnostic of any active infection, be it viral, bacterial, fungal, or caused by another pathogen;
- •Participants who have contraindication to undergo any of the tests performed in this study, for example, have pacemakers or surgical clip;
- •History of alcohol or illegal drugs abusers;
- •History of 1 or more episodes of suicide in the two years before Visit V-4;
- •Active smoker or have stopped smoking less than six months prior to enrollment;
- •Test positive in at least one of the serological tests: HIV 1 and 2 (Anti-HIV-1,2), HTLV I and II, HBV (HBsAg, anti-HBc), HCV (anti-HCV-Ab) and VDRL (Treponema pallidum);
- •History of drug allergy, including contrasts for imaging, or bovine products;
- •In use or expected use of immunosuppressive drugs or prohibited medicines for the first three months after the first administration of the investigational product;
- •Any clinical changes that is interpreted by the medical researcher as a risk to participant's enrollment.
结局指标
主要结局
Safety of Cellavita HD by periodic monitoring changes at adverse events, vital signs, laboratory tests, ECG and incidence of benign and malignant neoplasms
时间窗: first year and in the following 4 years
The safety of the investigational product will be evaluated in detail from periodic evaluations contemplating monitoring changes of: * Adverse events including type, frequency, intensity, seriousness, severity, and action taken related to the investigational product study; * Vital signs (BP, HR, axillary temperature), physical and medical examination (BMI, weight, height, medical condition - cardiovascular, pulmonary, digestive, musculoskeletal and peripheral, with emphasis on the neurological assessment and others); * Laboratory tests included hematologic, biochemical, urologic and serological analysis; * Electrocardiogram (ECG) of 12 derivations; * Incidence and classification of benign and malignant neoplasms in the following organs/systems: CNS, lung, liver, spleen, pancreas, prostate, testicle, urinary, hematological and skeletal system through the laboratory tests, magnetic resonance imaging, computerized tomography and ultrasonography.
次要结局
- Preliminary efficacy of Cellavita HD by UHDRS improvement and global clinical response (CIBIS)(first year and in the following 4 years)
- Preliminary efficacy of Cellavita HD by comparison of the CNS assessment(first year)
- Preliminary efficacy of Cellavita HD by comparison of the inflammatory markers(first year)
- Immunological Response of Cellavita HD(first year)
- Risk of suicidal ideation by Hamilton Depression Rating Scale (HDRS)(first year and in the following 4 years)