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

November 1, 2022 updated by: Azidus Brasil

First in Human Study to Evaluate Safety of Cellavita HD Investigational Product After Intravenous Application in Participants With Huntington's Disease

Cellavita HD is a stem-cell therapy for Huntington's Disease. This is a first-in-human, non-randomized, phase I study in which participants with Huntington's Disease will receive three intravenous injections and will be followed for 5 years to evaluate safety and tolearability of product and preliminary evidence of effectiveness.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a first-in-human, 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 be composed by the register of adverse events (including type, frequency, intensity, seriousness, severity, and action taken related to the investigational product), could be include changes in vital signs, physical and medical evaluations, laboratory or serology tests and electrocardiogram (ECG), and by the incidence of benign and malign neoplasms. Preliminary evidence of efficacy will be evaluated by global clinical improvement (CIBIS) and evolution of disease improvement (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). Fluctuation in suicide tendency grade will be evaluated by Hamilton Depression Rating Scale (HDRS).The immunological response of HD product over the administration period will be evaluated by CD4+ and CD8+ proliferation and inflammatory markers release.

Participants who show evidence of loss of clinical benefit achieved over the course of treatment verified through worsening greater or equal to that expected for the natural course of the disease on motor, cognitive, behavioral and functional capacity symptoms assessed by the UHDRS scale, will receive additional doses of the product as long as there is clinical benefit at the Investigator's discretion and/or until the product is marketed. The same dose used by the subject during the treatment period will be administered throughout the period of additional doses.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • São Paulo
      • Valinhos, São Paulo, Brazil, 13271-130
        • Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Sign and date ICF;
  • Ability to follow instructions as well as ability to understand and fulfill the study requirements correctly;
  • 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;
  • Any medical observation data (clinical and physical) that medical research judge as a risk for subject if enrollment at the study;
  • Any laboratory exam data that medical research judge as a risk for subject if enrollment at the study;
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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/weight range 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. All participants will receive a total of 3 intravenous administration, one every 30 days.
Other Names:
  • 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/weight range 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. All participants will receive a total of 3 intravenous administration, one every 30 days.
Other Names:
  • cellular therapy, mesenchymal stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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: first year and in the following 4 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;
  • 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.
first year and in the following 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preliminary efficacy of Cellavita HD by UHDRS improvement and global clinical response (CIBIS)
Time Frame: first year and in the following 4 years
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.
first year and in the following 4 years
Preliminary efficacy of Cellavita HD by comparison of the inflammatory markers
Time Frame: first 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).
first year
Immunological Response of Cellavita HD
Time Frame: first 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.
first year
Preliminary efficacy of Cellavita HD by comparison of the CNS assessment
Time Frame: first 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.
first year
Risk of suicidal ideation by Hamilton Depression Rating Scale (HDRS)
Time Frame: first year and in the following 4 years
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).
first year and in the following 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azidus Brasil

Collaborators

Cellavita Pesquisa Científica Ltda
Azidus Brasil Scientific Research and Development Ltda

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2017

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

March 11, 2016

First Submitted That Met QC Criteria

April 4, 2016

First Posted (Estimate)

April 5, 2016

Study Record Updates

Last Update Posted (Actual)

November 2, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAVE-DH
  • 51005115.9.0000.5412 (Registry Identifier: CAAE)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data of the study will become public.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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