Dose-response Evaluation of the Cellavita HD Product in Patients With Huntington's Disease

Azidus Brasil49 enrolled

Overview

Cellavita HD is a stem-cell therapy for Huntington's Disease. This is a prospective, phase II, single-center, randomized (2:2:1), triple-blind, placebo controlled study, with two test doses of Cellavita HD product.

This is a phase II dose-response study in which participants with HD will receive three intravenous injections of the investigational product or placebo (one every month for three months) a total of three cycles. The subjects will be randomized in 2: 2: 1 ratio for the groups G1: lower dose (1x10\^6 cells/weight range), G2: higher dose (2x10\^6 cells/weight range) or G3: placebo. To identify the dose of the product that will provide the best clinical response, motor assessment will be performed with UHDRS scale and improvement will be evaluated by correlating before and after treatment scores. Additionally, also will be performed the combined score through the cUHDRS. Secondary evidences of efficacy will be evaluated through the data of functional state, total functional capacity, functional independence, psychiatric symptoms and cognition from UHDRS scale. Additionally, related data to clinical worsening, change of Body Mass Index (BMI), risk of suicide attempt and neurological image improvement will be evaluated. Safety evaluation will included the incidence and classification of the adverse events experienced by the subjects during the study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Huntington Disease

Interventions

Cellavita HD lower doseBIOLOGICAL

The participants will receive a total of 9 intravenous administrations of 1x10\^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Cellavita HD higher doseBIOLOGICAL

The participants will receive a total of 9 intravenous administrations of 2x10\^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

PlaceboOTHER

The participants will receive a total of 9 intravenous administrations of placebo divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Eligibility

Sex: ALLMin age: 21 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Provide a written, signed and dated Informed Consent Form; 2. Male and female subjects aged ≥ 21 and ≤ 65 years; 3. Have a confirmatory diagnosis report (PCR) of Huntington's disease with a number of CAG repeats in chromosome 4 higher than or equal to 40, and lower than or equal to 50 (if the subject did not perform the exam and/or if he/she does not have an available result for this exam, a new exam must be performed); 4. A score of 5 points or higher for the motor evaluation of the UHDRS scale (Unified Huntington's Disease Rating Scale) at enrollment; 5. Score of 8 to 11 points for the functional capacity of the UHDRS scale at enrollment. Exclusion Criteria: 1. Subject who participated in clinical trials protocols within the last twelve (12) months (Resolution CNS 251, August 7, 1997, item III, subitem J), unless, at the investigator's opinion, the subject would have a direct benefit from it; 2. Diagnosis of juvenile Huntington's disease; 3. Diagnosis of epilepsy; 4. Diagnosis of major cognitive disorder; 5. Active decompensated psychiatric illness; 6. Current or prior history of neoplasm; 7. Current history of gastrointestinal, hepatic, renal, endocrine, pulmonary, hematological, immunological, metabolic pathology or severe uncontrolled cardiovascular diseases; 8. Diagnosis of any active infection, whether viral, bacterial, fungal or caused by another pathogen; 9. Subject with contraindication to the exams performed in this study, for example, with pacemaker or surgical clip; Alcohol and drugs abuse (previously diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders - DSM V criteria); 10. Use of illegal drugs; 11. Tabagism; 12. Smoker or quit smoking for less than 6 months; 13. Positive result in one of the serum tests: HIV 1 and 2 (Anti-HIV-1,2), HTLV I and II, HBV (HBsAg, Anti-HBc), HCV (anti-HCV-Ab) and FTA-ABS (Treponema pallidum); 14. History of drug allergy, including to contrast agents used in imaging tests or bovine-derived products; 15. Using or expects to use immunosuppressant drugs or forbidden drugs (item 5.3) during the first three months after the first administration of the investigational product; 16. Any clinical change that the investigator considers a risk to subject's enrollment in the study.

Locations (1)

Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.

Valinhos, São Paulo, Brazil

Outcomes

Primary Outcomes

Efficacy by UHDRS-TMS

The primary endpoint was the rate of change (slope) in Unified Huntington's Disease Rating Scale - Total Motor Score from V0 to V11 (minimum 0, the best; and maximum 124, the worst). For each participant, a regression line was fitted (Y = a + bx), where b represents the individual slope, reflecting the annualised rate of motor progression. A negative slope suggests improvement or slower decline; a positive slope indicates worsening. To compare treatment efficacy, the slopes were analysed using a Mixed Model for Repeated Measures (MMRM), which accounts for intra-subject variability and missing data. This approach allowed estimation and comparison of average slopes between each treated group and placebo, providing a robust measure of motor function trajectory over time.

Time frame: monthly for eleven months

Secondary Outcomes

Efficacy by UHDRS-TFC

Assessed by the rate of change (slope) from V0 to V11 in the UHDRS-TFC. The response of each participant or means of all participants was evaluated by the slopes of each regression line of UHDRS-TFC determined as follows: The equation describes the regression line: Y = a + bx, where: * "Y" is the dependent variable. * "a" is the constant that represents the intersection of the line with the vertical axis. * "b" is the angular coefficient, that is, the slope. * "x" is the independent variable. Therefore, the 'b' value represents the slope of the straight line that best fits the values collected from the baseline (V0) to the value of V11, using the least squares method. This slope corresponds to the estimated annualized individual variation of UHDRS-TFC during the given period.

Time frame: monthly for eleven months

Data from ClinicalTrials.gov

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