Efficacy and Safety of NestaCell® in Huntington's Disease (STAR)

October 18, 2023 updated by: Azidus Brasil

Phase III Efficacy and Safety of NestaCell® in Moderated Huntington's Disease

Huntington's disease (HD) is a rare neurodegenerative condition caused by increased CAG trinucleotide repeats in the HTT gene, on chromosome 4. The estimated global prevalence is 2.71 cases per 100,000 inhabitants. In Brazil, it is estimated that 13,000 to 19,000 people carry the gene and 65,000 to 95,000 are descendants at risk.

HD usually manifests itself in the fourth decade of life with motor, cognitive and behavioral symptoms, such as chorea. This condition profoundly affects quality of life and there is no treatment that can modify its course. Tetrabenazine is the only medication approved to control chorea.

A partnership between the Butantan Institute and Cellavita investigates the use of Human Dental Pulp Stem Cells (hDPSCs) to treat HD. NestaCell® was developed, a product based on these cells, which express high levels of BDNF, an important neurotrophic factor for neuronal survival.

Preclinical tests showed that NestaCell® is distributed to several organs, including the central nervous system, being well tolerated in toxicological tests in rats.

In phase I (SAVE) and phase II (ADORE) clinical trials, NestaCell® was administered to patients with HD. The results indicated a significant improvement in motor scores and functional capacity compared to placebo, demonstrating a clinically significant benefit.

NestaCell® also presented a good safety and tolerability profile, with few adverse events related to the product. The results support the conclusion that NestaCell® is safe and well tolerated in HD patients, within the doses tested.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase III multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of Nestacell® in Huntington's Disease.

After signing the Informed Consent Form (ICF) the patients will perform the V-2 and V-1 screening procedures. In the V-2 the site collects personal data and a physician clinically confirms the HD diagnosis. The patient collects blood for CAG repeats and safety exams. Females with childbearing potential perform a urine pregnancy test. In the V-1 the investigator remotely reviews the results of the V-2 exams and authorizes the performance of the V-1 radiological exams (MRI and Total-Body PET Scan) in the radiology center.

In the V0, the PI and his team perform the baseline UHDRS and body weight assessments. The patient will be randomized to Nestacell® or placebo. Those weighing 50 to 67.9 kg will receive 100 million cells (or placebo) and those weighing ≥ 68 kg will receive 136 million cells(or placebo) per administration. The doses are based on the V0 weight assessment and will not change throughout the study unless the PI asks for safety reasons (for example, a relevant weight loss).

The V1 marks the first investigational product administration. It will happen in sites unrelated to those performing the outcomes evaluation by personnel specially trained to prepare and administer the investigational product. After the females with childbearing potential performe the urine pregnancy test, NestaCell® or placebo will be administered intravenously in three cycles of three-monthly administrations with a monthly interval between cycles (total of 9 administrations). The other administrations happen at visits V2, V3, V5, V6, V7, V9, V10, and V11. To assure blindness, UHDRS and other clinical evaluations will be carried out in the research center [by the principal investigator (PI)] while the administrations will be made in the Center for the Investigational Product Administration (CIPA). The outcome evaluations by the PI and his/her team happen at V4, V8, and V12, one month after the end of each cycle. In the V13, the patients will also be directed to the radiology center to repeat the MRI exam.

Each patient participates in the trial for approximately 14 months, two months for screening, and twelve months for investigational product administration and follow-up.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

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

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female;
  2. Age from 18 to 55 years;
  3. HD diagnostic confidence level (DCL) score of 3 or 4 at enrolment;
  4. HD manifestations begin from 4 to 8 years before enrolment;
  5. UHDRS Total Functional Capacity (TFC) from 7 to 12, suggesting mild-moderate functional impairment;
  6. Body weight at the V -1 from 50 to 90 Kg;
  7. CAG repeats from 40 to 50;
  8. ICF signature.

Exclusion Criteria:

  1. Juvenile Huntington's disease,
  2. Concomitant epilepsy;
  3. Decompensated psychiatric disorders;
  4. History of a suicide attempt;
  5. Other neurological or musculoskeletal disorders that might interfere with the assessments;
  6. Prior use of gene or cell therapy.
  7. Confirmed or suspected cancer within the last 1 year (except operated basal cell carcinoma);
  8. History of allergy to imaging exams contrast, or bovine origin products;
  9. Current or planned use of immunosuppressants;

  10. Clinically significant changes in the safety exams, defined as;

    • Serum transaminases (ALT, AST) increased > 2.5 × upper limit of normality (ULN).
    • Absolute neutrophil count in peripheral blood < 3,000 cells/1 mm3.
    • Serum creatinine > 2 × age- and sex-specific ULN.
    • Positive serology for HIV 1 and 2 (Anti-HIV-1,2), HTLV I and II, HBV (HBsAg, Anti-HBc), HCV (anti-HCV-Ab), and FTA-ABS.
    • Amylase, Troponin I, CKmB increased > 2.0 × ULN.
    • Malignancy shown by the Total-Body PET Scan.
    • Glycated hemoglobin > 6.5%.
    • aPTT, TT, platelets > 2.5 x ULN.
  11. Pregnancy, lactation, or pregnancy plan;
  12. BMI less than 18.5 at enrolment;
  13. Participation in a clinical trial within twelve months before inclusion;
  14. History of surgical procedures aiming at improving symptoms of Huntington's disease, such as neural transplantations, lesions of the central nervous system, infusions of neurotrophic agents, or deep brain stimulation.
  15. Any medical condition that makes the patient unsuitable for the study or increases the risk of participation at the investigator's discretion.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Arm 1: Nine intravenous placebo administrations in twelve months.
Genetic: NestaCell®
Human Dental Pulp Stem Cells (hDPSCs).
Experimental: Intravenous NestaCell® administrations
Arm 2: Nine intravenous NestaCell® administrations in twelve months.
Genetic: NestaCell®
Human Dental Pulp Stem Cells (hDPSCs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Efficacy Objective
Time Frame: 1 year
Proportion of patients who stabilized or decreased the UHDRS-TMS from Visit 0 to Visit 12 in the Nestacell® vs. Placebo groups.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Efficacy Objectives
Time Frame: 1 year
Mean variation of the UHDRS-TMS mean variation from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Proportion of patients who stabilized or increased the UHDRS-TFC from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Mean variation of the UHDRS-TFC from Visit 0 to Visit 12 of the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Proportion of patients who stabilized or increased the cUHDRS from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Mean variation of the cUHDRS from Visit 0 to Visit 12 of the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Proportion of patients who stabilized the MRI outcomes: 7.1 white substance, 7.2 gray substance, from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Mean variation of the MRI outcomes: 8.1 white substance, 8.2 gray substance, from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Proportion of patients who stabilized or decreased the NfL blood levels from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.
1 year
Secondary Efficacy Objectives
Time Frame: 1 year
Mean variation of the NfL blood levels from Visit 0 to Visit 12 of the groups Nestacell® and Placebo.
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Safety Objective
Time Frame: 1 year
Occurrence, severity and cause of adverse events related to the study drug
1 year
Exploratory objectives
Time Frame: 1 year
Blood concentration of nestin, IL-6, IL-17, TNFα, IFN-γ, C-reactive protein, BDNF, PT, aPTT, and D-dimer and the saliva concentration of BDNF and huntingtin before and 24 h after the NestaCell® administration at V1 and in a subset of 20-30 HD patients.
1 year
Exploratory objectives
Time Frame: Up to 9 months
Blood concentration of nestin, IL-6, IL-17, TNFα, IFN-γ, C-reactive protein, BDNF, PT, aPTT, and D-dimer and the saliva concentration of BDNF and huntingtin before and 24 h after the NestaCell® administration at V9 in a subset of 20-30 HD patients.
Up to 9 months
Exploratory objectives
Time Frame: Up to 9 months
Evolution between V1 and V9 of the blood concentration of nestin, IL-6, IL-17, TNFα, IFN-γ, C-reactive protein, BDNF, PT, aPTT, and D-dimer and the saliva concentration of BDNF and huntingtin before the NestaCell® administration in a subset of 20-30 HD patients
Up to 9 months
Exploratory objectives
Time Frame: Up to 9 months
Evolution between V1 and V9 of the blood concentration of nestin, IL-6, IL-17, TNFα, IFN-γ, C-reactive protein, BDNF, PT, aPTT, and D-dimer and the saliva concentration of BDNF and huntingtin 24 hours after the NestaCell® administration in a subset of 20-30 HD patients.
Up to 9 months
Exploratory objectives
Time Frame: 1 year
Measure of the relative amount of study participants who experienced changes in hair color during the course of the study.Nestacell® and placebo groups.
1 year
Exploratory objectives
Time Frame: 1 year
Measure of the relative number of study participants who experienced hair growth.
1 year

Collaborators and Investigators

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

Sponsor

Azidus Brasil

Collaborators

Cellavita Pesquisa Científica Ltda

Investigators

  • Study Director: Luciana Ferrara, Doctor, Azidus Brasil

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 (Estimated)

June 8, 2024

Primary Completion (Estimated)

September 8, 2025

Study Completion (Estimated)

February 9, 2026

Study Registration Dates

First Submitted

October 5, 2023

First Submitted That Met QC Criteria

October 18, 2023

First Posted (Actual)

October 24, 2023

Study Record Updates

Last Update Posted (Actual)

October 24, 2023

Last Update Submitted That Met QC Criteria

October 18, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STAR
  • U1111-1298-5627 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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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