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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03252535
Recruitment Status : Active, not recruiting
First Posted : August 17, 2017
Last Update Posted : December 13, 2019
Sponsor:
Collaborator:
Cellavita Pesquisa Científica Ltda
Information provided by (Responsible Party):
Azidus Brasil

Tracking Information
First Submitted Date  ICMJE August 15, 2017
First Posted Date  ICMJE August 17, 2017
Last Update Posted Date December 13, 2019
Actual Study Start Date  ICMJE January 15, 2018
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2019)
Effective Dose [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 16, 2017)
Effective Dose [ Time Frame: one year ]
Consists of identifying the dose of the product Cellavita HD providing the best clinical response.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2019)
  • Clinical neurological worsening over the treatment [ Time Frame: monthly for fourteen months ]
    The clinical neurological worsening over the treatment will be evaluated by specific UHDRS domain.
  • BMI assessment [ Time Frame: monthly for fourteen months ]
    The BMI (Body Mass Index) will be assessed through the BMI profiles obtained during the treatment.
  • Risk of suicidal ideation [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2017)
  • Improvement of UHDRS domains [ Time Frame: one year ]
    Will evaluate of the functional state, total functional capacity, functional independence, psychiatric symptoms and cognition through UHDRS scale before and throught the study.
  • Clinical worsing over the treatment [ Time Frame: one year ]
    The clinical worsing over the treatment will be evaluated by specific UHDRS domain.
  • BMI assessment [ Time Frame: one year ]
    The BMI (Body Mass Index) will be assessed through the BMI profiles obtained during the treatment.
  • Risk of suicidal ideation [ Time Frame: one year ]
    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 [ Time Frame: one year ]
    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.
Current Other Pre-specified Outcome Measures
 (submitted: December 11, 2019)
  • Safety administration of Cellavita HD product [ Time Frame: 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.
  • Prognosis of Huntington Disease [ Time Frame: 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.
Original Other Pre-specified Outcome Measures
 (submitted: August 16, 2017)
  • Safety administration of Cellavita HD product [ Time Frame: approximately two years ]
    Will be carefully evaluated from the periodical assessments including clinical, laboratory, and imaging exams, so that any change is properly recorded.
  • Prognosis of Huntington Disease [ Time Frame: one year ]
    This parameter will be evaluated by statistical comparison of NF-L (biological marker) results observed at baseline period and other analysed times.
 
Descriptive Information
Brief Title  ICMJE Dose-response Evaluation of the Cellavita HD Product in Patients With Huntington's Disease
Official Title  ICMJE Dose-Response Evaluation of the Investigational Product Cellavita HD After Intravenous Administration in Patients With Huntington's Disease
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Huntington Disease
Intervention  ICMJE
  • 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 Name: cellular therapy, mesenchymal stem cells
  • 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 Name: cellular therapy, mesenchymal stem cells
  • 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 Name: physiological solution without cells
Study Arms  ICMJE
  • 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).
    Intervention: Biological: Cellavita HD lower dose
  • 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).
    Intervention: Biological: Cellavita HD higher dose
  • 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).
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 16, 2017)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03252535
Other Study ID Numbers  ICMJE ADORE-DH
52375916.1.0000.5412 ( Other Identifier: CAAE )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data will become public.
Responsible Party Azidus Brasil
Study Sponsor  ICMJE Azidus Brasil
Collaborators  ICMJE Cellavita Pesquisa Científica Ltda
Investigators  ICMJE
Principal Investigator: Joyce Macedo da Silva, MD Azidus Brasil Scientific Research and Development Ltda
PRS Account Azidus Brasil
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP