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

Phase 2

Completed

• Conditions: Huntington Disease
• Interventions: Biological: Cellavita HD higher dose; Biological: Cellavita HD lower dose; Other: Placebo

• Registration Number: NCT03252535
• Lead Sponsor: Azidus Brasil

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2017-08-15
• Study First Submitted QC: 2017-08-16
• Study First Posted: 2017-08-17
• Study Start: 2018-01-15
• Primary Completion: 2021-03-23
• Study Completion: 2021-04-30
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-26
• Last Update Posted: 2022-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cellavita HD Higher Dose	Cellavita HD higher dose	The participants randomized to this group 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).
Cellavita HD Lower Dose	Cellavita HD lower dose	The participants randomized to this group 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).
Placebo Group	Placebo	The participants randomized to this group will receive a total of 9 intravenous administrations divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Primary Outcome Measures

Name	Time	Method
Effective Dose	monthly for fourteen months	Consists of identifying the dose of the product Cellavita HD providing the best clinical response. It will be verified through the baseline Unified Huntington's Disease Rating Scale (UHDRS) score from the end of treatment (motor, cognitive, behavioral, functional capacity and independence domains). Additionally, also will be performed the combined score through the cUHDRS.

Secondary Outcome Measures

Name	Time	Method
BMI assessment	monthly for fourteen months	The BMI (Body Mass Index) will be assessed through the BMI profiles obtained during the treatment.
Clinical neurological worsening over the treatment	monthly for fourteen months	The clinical neurological worsening over the treatment will be evaluated by specific UHDRS domain.
Risk of suicidal ideation	monthly for fourteen months	Will be evaluated by suicidal domain from Hamilton Depression Scale (HAM-D). The classificatory punctuation may correspond to mild depression (score: 8 to 13), moderate depression (score: 19 - 22) and severe depression (score: \> 23).
CNS assessment	baseline and one year later	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.
Clinical Interview Based impression of Severity (CIBIS)	monthly for fourteen months	A general global assessment tool for disease severity that associates the impression of a medical interviewer with a patient / caregiver opinion. After observing the data obtained during the clinical interview, the interviewer records the appropriate score.

Trial Locations

Locations (1)

Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.; 🇧🇷 Valinhos, São Paulo, Brazil