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

Primary Purpose

Huntington Disease

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Cellavita HD lower dose
Cellavita HD higher dose
Placebo
Sponsored by
Azidus Brasil
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington Disease focused on measuring Huntington disease, Stem cell therapy, Dental pulp stem cell

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Cellavita HD Lower Dose

Cellavita HD Higher Dose

Placebo Group

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

Effective Dose
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

Clinical neurological worsening over the treatment
The clinical neurological worsening over the treatment will be evaluated by specific UHDRS domain.
BMI assessment
The BMI (Body Mass Index) will be assessed through the BMI profiles obtained during the treatment.
Risk of suicidal ideation
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
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)
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.

Full Information

First Posted
August 15, 2017
Last Updated
October 26, 2022
Sponsor
Azidus Brasil
Collaborators
Cellavita Pesquisa Científica Ltda
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1. Study Identification

Unique Protocol Identification Number
NCT03252535
Brief Title
Dose-response Evaluation of the Cellavita HD Product in Patients With Huntington's Disease
Acronym
ADORE-DH
Official Title
Dose-Response Evaluation of the Investigational Product Cellavita HD After Intravenous Administration in Patients With Huntington's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
January 15, 2018 (Actual)
Primary Completion Date
March 23, 2021 (Actual)
Study Completion Date
April 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Azidus Brasil
Collaborators
Cellavita Pesquisa Científica Ltda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
Keywords
Huntington disease, Stem cell therapy, Dental pulp stem cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes 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).
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cellavita HD Lower Dose
Arm Type
Experimental
Arm Description
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).
Arm Title
Cellavita HD Higher Dose
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
Cellavita HD lower dose
Other Intervention Name(s)
cellular therapy, mesenchymal stem cells
Intervention Description
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).
Intervention Type
Biological
Intervention Name(s)
Cellavita HD higher dose
Other Intervention Name(s)
cellular therapy, mesenchymal stem cells
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
physiological solution without cells
Intervention Description
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).
Primary Outcome Measure Information:
Title
Effective Dose
Description
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.
Time Frame
monthly for fourteen months
Secondary Outcome Measure Information:
Title
Clinical neurological worsening over the treatment
Description
The clinical neurological worsening over the treatment will be evaluated by specific UHDRS domain.
Time Frame
monthly for fourteen months
Title
BMI assessment
Description
The BMI (Body Mass Index) will be assessed through the BMI profiles obtained during the treatment.
Time Frame
monthly for fourteen months
Title
Risk of suicidal ideation
Description
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).
Time Frame
monthly for fourteen months
Title
CNS assessment
Description
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
baseline and one year later
Title
Clinical Interview Based impression of Severity (CIBIS)
Description
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.
Time Frame
monthly for fourteen months
Other Pre-specified Outcome Measures:
Title
Safety administration of Cellavita HD product
Description
Will be carefully evaluated from the periodical assessments including clinical, laboratory, and imaging exams, so that any change is properly recorded.
Time Frame
monthly for fourteen months
Title
Prognosis of Huntington Disease
Description
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.
Time Frame
baseline and one year later

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provide a written, signed and dated Informed Consent Form; Male and female subjects aged ≥ 21 and ≤ 65 years; 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); A score of 5 points or higher for the motor evaluation of the UHDRS scale (Unified Huntington's Disease Rating Scale) at enrollment; Score of 8 to 11 points for the functional capacity of the UHDRS scale at enrollment. Exclusion Criteria: 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; Diagnosis of juvenile Huntington's disease; Diagnosis of epilepsy; Diagnosis of major cognitive disorder; Active decompensated psychiatric illness; Current or prior history of neoplasm; Current history of gastrointestinal, hepatic, renal, endocrine, pulmonary, hematological, immunological, metabolic pathology or severe uncontrolled cardiovascular diseases; Diagnosis of any active infection, whether viral, bacterial, fungal or caused by another pathogen; 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); Use of illegal drugs; Tabagism; Smoker or quit smoking for less than 6 months; 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); History of drug allergy, including to contrast agents used in imaging tests or bovine-derived products; 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; Any clinical change that the investigator considers a risk to subject's enrollment in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joyce Macedo da Silva, MD
Organizational Affiliation
Azidus Brasil Scientific Research and Development Ltda
Official's Role
Principal Investigator
Facility Information:
Facility Name
Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.
City
Valinhos
State/Province
São Paulo
ZIP/Postal Code
13271-130
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data will become public.
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Dose-response Evaluation of the Cellavita HD Product in Patients With Huntington's Disease

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