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Safety Evaluation of Cellavita HD Administered Intravenously in Participants With Huntington's Disease (SAVE-DH)

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ClinicalTrials.gov Identifier: NCT02728115
Recruitment Status : Active, not recruiting
First Posted : April 5, 2016
Last Update Posted : June 20, 2018
Sponsor:
Collaborators:
Cellavita Pesquisa Científica Ltda
Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda
Information provided by (Responsible Party):
Azidus Brasil

Brief Summary:
Cellavita HD is a stem-cell therapy for Huntington's Disease. This is a first-in-human, dose escalation study in which participants with Huntington's Disease will receive 3 intravenous injections and will be followed for 5 years to evaluate safety and preliminary evidence of effectiveness.

Condition or disease Intervention/treatment Phase
Huntington Disease Biological: Cellavita HD Lower Dose Biological: Cellavita HD Higher dose Phase 1

Detailed Description:
This is a first-in-human, dose escalation, non-randomized phase I study in which participants with HD will receive three intravenous injections of one of two doses of the investigational product, one every month for three months. Safety evaluation data will include report of all adverse events (including type, frequency, intensity, seriousness, severity, and action taken related to the investigational product study), changes in vital signs, physical examination and medical evaluations, changes in laboratory or serology tests and electrocardiogram (ECG), and incidence and classification of benign and malignant neoplasms. Preliminary evidence of efficacy will be evaluated by clinical improvement of motor, cognitive and behavioral degradation through Unified Huntington's Disease Rating Scale (UHDRS) and inflammatory markers: IL-4, IL-6, IL-10 (interleukin IL) e TNF-alpha (tumoral necrosis factor alpha); CNS improvement will be assessed by magnetic resonance imaging (MRI). The immunological response of HD product over the administration period will be evaluated by CD4+ and CD8+ proliferation and inflammatory markers release.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: First in Human Study to Evaluate Safety of Cellavita HD Investigational Product After Intravenous Application in Participants With Huntington's Disease
Actual Study Start Date : October 16, 2017
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cellavita HD Lower Dose
Participants assigned to this arm will receive 3 administrations, one every 30 days, of 1x10^6 cells / kg per administration of Cellavita HD (n= 3) .
Biological: Cellavita HD Lower Dose
The first three participants enrolled in the study will be assigned to the lower dose arm with staggered treatment, with an interval of 30 days between the first administration of the first participant and the first administration of the second participant assigned to this arm. Both participants will receive a total of 3 intravenous administration, one every 30 days.
Other Name: cellular therapy, mesenchymal stem cells

Experimental: Cellavita HD Higher dose
Participants assigned to this arm will receive 3 administrations, one every 30 days, of 2x10^6 cells / kg per administration of Cellavita HD (n= 3).
Biological: Cellavita HD Higher dose
The last three participants enrolled in the study will be assigned to the higher dose arm with staggered treatment, with an interval of 30 days between the first administration of the first participant and the first administration of the second participant assigned to this arm. Both participants will receive a total of 3 intravenous administration, one every 30 days.




Primary Outcome Measures :
  1. Safety of Cellavita HD by periodic monitoring changes at adverse events, vital signs, laboratory tests, ECG and incidence of benign and malignant neoplasms [ Time Frame: five years ]

    The safety of the investigational product will be evaluated in detail from periodic evaluations contemplating monitoring changes of:

    • Adverse events including type, frequency, intensity, seriousness, severity, and action taken related to the investigational product study;
    • Vital signs (BP, HR, axillary temperature), physical and medical examination (BMI, weight, height, medical condition - cardiovascular, pulmonary, digestive, musculoskeletal and peripheral, with emphasis on the neurological assessment and others);
    • Laboratory tests included hematologic, biochemical, urologic and serological analysis;
    • Electrocardiogram (ECG) of 12 derivations;
    • And incidence and classification of benign and malignant neoplasms in the following organs/systems: CNS, lung, liver, spleen, pancreas, prostate, testicle, urinary, hematological and skeletal system through the laboratory tests, magnetic resonance imaging, computerized tomography and ultrasonography.


Secondary Outcome Measures :
  1. Preliminary efficacy of Cellavita HD by global clinical response and UHDRS improvement [ Time Frame: one year ]
    Will be evaluated by statistical comparison of the results of each UHDRS scale component: motor, cognitive and behavior. The global clinical response will be assessed by statistical comparison between baseline score observed by the Investigator before and after Cellavita HD treatment.

  2. Preliminary efficacy of Cellavita HD by comparison of the inflammatory markers [ Time Frame: one year ]
    Will be evaluated by statistical comparison of the inflammatory markers included IL-4, IL-6, IL-10 (interleukin IL) and TNF-alpha (tumoral necrosis factor alpha).

  3. Immunological Response of Cellavita HD [ Time Frame: one year ]
    The immunological response induced by Cellavita HD will be evaluated by statistical comparison between baseline results of CD4+ and CD8+ proliferation and the other evaluated times.

  4. Preliminary efficacy of Cellavita HD by comparison of the 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.

  5. Risk of suicidal ideation by Hamilton Depression Scale [ Time Frame: one year ]
    Will be evaluated by suicidal domain. The classificatory pontuation may correspond to mild depression (score: 8 to 13), moderate depression (score: 19 - 22) and severe depression (score: > 23).



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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Sign and date ICF;
  • Male participant aged ≥ 21 and ≤ 65;
  • Participants who submit medical report (PCR) attesting Huntington's disease with a number of CAG repeats on chromosome 4, greater than or equal to 40 and less than or equal to 50 (if the participant has not performed the examination and/or if he does not have the report available, a new exam should be done);
  • Score 5 points or more in motor assessment UHDRS scale (Unified Huntington's Disease Rating Scale) at the time of enrollment;
  • Score between 8 and 11 points in the functional capacity of the UHDRS scale at the time of enrollment.

Exclusion Criteria:

  • Participation within 12 months in any clinical trial;
  • Juvenile Huntington disease diagnosis;
  • History of epilepsy;
  • Diagnostic of major cognitive impairment;
  • Active decompensated psychiatric disease;
  • Current or prior history of neoplasia;
  • Current history of gastrointestinal, hepatic, renal, endocrine, pulmonary, hematologic, immune, metabolic pathology or severe and uncontrolled cardiovascular disease;
  • Diagnostic of any active infection, be it viral, bacterial, fungal, or caused by another pathogen;
  • Participants who have contraindication to undergo any of the tests performed in this study, for example, have pacemakers or surgical clip;
  • History of alcohol or illegal drugs abusers;
  • History of 1 or more episodes of suicide in the two years before Visit V-4;
  • Active smoker or have stopped smoking less than six months prior to enrollment;
  • Test positive in at least one of the serological tests: HIV 1 and 2 (Anti-HIV-1,2), HTLV I and II, HBV (HBsAg, anti-HBc), HCV (anti-HCV-Ab) and VDRL (Treponema pallidum);
  • History of drug allergy, including contrasts for imaging, or bovine products;
  • In use or expected use of immunosuppressive drugs or prohibited medicines for the first three months after the first administration of the investigational product;
  • Any clinical changes that is interpreted by the medical researcher as a risk to participant's enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02728115


Locations
Brazil
Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.
Valinhos, São Paulo, Brazil, 13271-130
Sponsors and Collaborators
Azidus Brasil
Cellavita Pesquisa Científica Ltda
Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda
Investigators
Study Director: Luciana Ferrara, CEO Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda

Publications:

Responsible Party: Azidus Brasil
ClinicalTrials.gov Identifier: NCT02728115     History of Changes
Other Study ID Numbers: SAVE-DH
51005115.9.0000.5412 ( Registry Identifier: CAAE )
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
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.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Azidus Brasil:
Huntington's Disease
Stem Cell
Dental Pulp Stem Cells

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Dementia
Chorea
Dyskinesias