Safety Evaluation of Cellavita HD Administered Intravenously in Participants With Huntington's Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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First in Human Study to Evaluate Safety of Cellavita HD Investigational Product After Intravenous Application in Participants With Huntington's Disease

Conditions
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Huntington Disease

Intervention / Treatment
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* Biological: Cellavita HD Lower Dose
* Biological: Cellavita HD Higher dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cellavita HD Lower Dose<br>Participants assigned to this arm will receive 3 administrations, one every 30 days, of 1x10^6 cells/weight range per administration of Cellavita HD (n= 3) . | Biological: Cellavita HD Lower Dose<br>* 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.<br>* Other names: cellular therapy, mesenchymal stem cells;|
| Experimental: Cellavita HD Higher dose<br>Participants assigned to this arm will receive 3 administrations, one every 30 days, of 2x10^6 cells/weight range per administration of Cellavita HD (n= 3). | Biological: Cellavita HD Higher dose<br>* 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.<br>* Other names: cellular therapy, mesenchymal stem cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | first year and in the following 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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). | 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. | 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. | 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). | first year and in the following 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington's Disease, Stem Cell, Dental Pulp Stem Cells