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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
6
The first three participants enrolled in the study will be assigned to the lower dose arm with staggered treatment, with an interval of 30 days between the first administration of the first participant and the first administration of the second participant assigned to this arm. All participants will receive a total of 3 intravenous administration, one every 30 days.
The last three participants enrolled in the study will be assigned to the higher dose arm with staggered treatment, with an interval of 30 days between the first administration of the first participant and the first administration of the second participant assigned to this arm. All participants will receive a total of 3 intravenous administration, one every 30 days.
Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.
Valinhos, São Paulo, Brazil
Safety of Cellavita HD by periodic monitoring changes at adverse events, vital signs, laboratory tests, ECG and incidence of benign and malignant neoplasms
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.
Time frame: first year and in the following 4 years
Preliminary efficacy of Cellavita HD by UHDRS improvement and global clinical response (CIBIS)
Will be evaluated by statistical comparison of the results of each UHDRS scale component: motor, cognitive and behavior. The global clinical response will be assessed by statistical comparison between baseline score observed by the Investigator before and after Cellavita HD treatment.
Time frame: first year and in the following 4 years
Preliminary efficacy of Cellavita HD by comparison of the inflammatory markers
Will be evaluated by statistical comparison of the inflammatory markers included IL-4, IL-6, IL-10 (interleukin IL) and TNF-alpha (tumoral necrosis factor alpha).
Time frame: first year
Immunological Response of Cellavita HD
The immunological response induced by Cellavita HD will be evaluated by statistical comparison between baseline results of CD4+ and CD8+ proliferation and the other evaluated times.
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Time frame: first year
Preliminary efficacy of Cellavita HD by comparison of the CNS assessment
Will be evaluated by statistical comparison of the CNS assessment through magnetic resonance image at cortical thickness measurements, volumes of different brain structures, especially the basal ganglia, with special attention to caudate and metabolic changes identified in proton spectroscopy.
Time frame: first year
Risk of suicidal ideation by Hamilton Depression Rating Scale (HDRS)
Will be evaluated by suicidal domain. The classificatory pontuation may correspond to mild depression (score: 8 to 13), moderate depression (score: 19 - 22) and severe depression (score: \> 23).
Time frame: first year and in the following 4 years