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

Sponsor
Azidus Brasil (Industry)
Overall Status
Completed
CT.gov ID
NCT03252535
Collaborator
Cellavita Pesquisa Científica Ltda (Other)
35
Enrollment
1
Location
3
Arms
39.5
Actual Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Cellavita HD lower dose
  • Biological: Cellavita HD higher dose
  • Other: Placebo
 Phase 2

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 (1x106 cells/weight range), G2: higher dose (2x106 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 Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
The study drugs will be provided in identical packages to maintain the study masking. Neither the Investigator nor the study team will know which drug the subject is receiving. In addition, the external outcome evaluator will receive the results in a codified manner (concealed).
Primary Purpose:
Treatment
Official Title:
Dose-Response Evaluation of the Investigational Product Cellavita HD After Intravenous Administration in Patients With Huntington's Disease
Actual Study Start Date :
Jan 15, 2018
Actual Primary Completion Date :
Mar 23, 2021
Actual Study Completion Date :
Apr 30, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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).

Biological: Cellavita HD lower dose
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).
Other Names:
  • cellular therapy, mesenchymal stem cells

    		•
    Experimental: 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).

    Biological: Cellavita HD higher dose
    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).
    Other Names:
  • cellular therapy, mesenchymal stem cells

    		•
    Placebo Comparator: Placebo Group

    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).

    Other: Placebo
    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).
    Other Names:
  • physiological solution without cells

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Clinical neurological worsening over the treatment [monthly for fourteen months]

      The clinical neurological worsening over the treatment will be evaluated by specific UHDRS domain.

    2. BMI assessment [monthly for fourteen months]

      The BMI (Body Mass Index) will be assessed through the BMI profiles obtained during the treatment.

    3. 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).

    4. 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.

    5. 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.

    Other Outcome Measures

    1. Safety administration of Cellavita HD product [monthly for fourteen months]

      Will be carefully evaluated from the periodical assessments including clinical, laboratory, and imaging exams, so that any change is properly recorded.

    2. Prognosis of Huntington Disease [baseline and one year later]

      This parameter will be evaluated by statistical comparison of NF-L (biological marker) results observed at baseline period and other analysed times. The results will be correlated to UHRDS scores.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda. Valinhos São Paulo Brazil 13271-130

    Sponsors and Collaborators

    • Azidus Brasil
    • Cellavita Pesquisa Científica Ltda

    Investigators

    • Principal Investigator: Joyce Macedo da Silva, MD, Azidus Brasil Scientific Research and Development Ltda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Azidus Brasil
    ClinicalTrials.gov Identifier:
    NCT03252535
    Other Study ID Numbers:
    • ADORE-DH
    • 52375916.1.0000.5412
    First Posted:
    Aug 17, 2017
    Last Update Posted:
    Jun 23, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Azidus Brasil
    Huntington disease
    Stem cell therapy
    Dental pulp stem cell
    Additional relevant MeSH terms:
    Huntington Disease

    Study Results

    No Results Posted as of Jun 23, 2021