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

Sponsor
Azidus Brasil (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT06097780
Collaborator
Cellavita Pesquisa Científica Ltda (Other)
120
Enrollment
2
Arms
20.1
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Genetic: NestaCell®
 Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The trial will evaluate 120 adult patients (male and female) aged 18 to 55 years with Huntington's disease:CAG repeats from 40 to 50; HD diagnostic confidence level (DCL) score of 4;UHDRS Total Functional Capacity (TFC) from 7 to 12, suggesting mild-moderate functional impairment. Each patient participates in the trial for approximately 14 months, two months for screening, and twelve months for investigational product administration and follow-up.The trial will evaluate 120 adult patients (male and female) aged 18 to 55 years with Huntington's disease:CAG repeats from 40 to 50; HD diagnostic confidence level (DCL) score of 4;UHDRS Total Functional Capacity (TFC) from 7 to 12, suggesting mild-moderate functional impairment. Each patient participates in the trial for approximately 14 months, two months for screening, and twelve months for investigational product administration and follow-up.
Masking:
Single (Outcomes Assessor)
Masking Description:
The trial will be two-armed double-blind (participant and investigator's team responsible for outcome assessments).
Primary Purpose:
Treatment
Official Title:
Phase III Efficacy and Safety of NestaCell® in Moderated Huntington's Disease
Anticipated Study Start Date :
Jun 8, 2024
Anticipated Primary Completion Date :
Sep 8, 2025
Anticipated Study Completion Date :
Feb 9, 2026

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

  1. Primary Efficacy Objective [1 year]

    Proportion of patients who stabilized or decreased the UHDRS-TMS from Visit 0 to Visit 12 in the Nestacell® vs. Placebo groups.

Secondary Outcome Measures

  1. Secondary Efficacy Objectives [1 year]

    Mean variation of the UHDRS-TMS mean variation from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.

  2. Secondary Efficacy Objectives [1 year]

    Proportion of patients who stabilized or increased the UHDRS-TFC from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.

  3. Secondary Efficacy Objectives [1 year]

    Mean variation of the UHDRS-TFC from Visit 0 to Visit 12 of the groups Nestacell® and Placebo.

  4. Secondary Efficacy Objectives [1 year]

    Proportion of patients who stabilized or increased the cUHDRS from Visit 0 to Visit 12 in the groups Nestacell® and Placebo.

  5. Secondary Efficacy Objectives [1 year]

    Mean variation of the cUHDRS from Visit 0 to Visit 12 of the groups Nestacell® and Placebo.

  6. Secondary Efficacy Objectives [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.

  7. Secondary Efficacy Objectives [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.

  8. Secondary Efficacy Objectives [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.

  9. Secondary Efficacy Objectives [1 year]

    Mean variation of the NfL blood levels from Visit 0 to Visit 12 of the groups Nestacell® and Placebo.

Other Outcome Measures

  1. Secondary Safety Objective [1 year]

    Occurrence, severity and cause of adverse events related to the study drug

  2. Exploratory objectives [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.

  3. Exploratory objectives [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.

  4. Exploratory objectives [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

  5. Exploratory objectives [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.

  6. Exploratory objectives [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.

  7. Exploratory objectives [1 year]

    Measure of the relative number of study participants who experienced hair growth.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  1. Pregnancy, lactation, or pregnancy plan;

  2. BMI less than 18.5 at enrolment;

  3. Participation in a clinical trial within twelve months before inclusion;

  4. 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.

  5. Any medical condition that makes the patient unsuitable for the study or increases the risk of participation at the investigator's discretion.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Azidus Brasil
  • Cellavita Pesquisa Científica Ltda

Investigators

  • Study Director: Luciana Ferrara, Doctor, Azidus Brasil

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Azidus Brasil
ClinicalTrials.gov Identifier:
NCT06097780
Other Study ID Numbers:
  • STAR
  • U1111-1298-5627
First Posted:
Oct 24, 2023
Last Update Posted:
Oct 24, 2023
Last Verified:
Oct 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Azidus Brasil
STAR
NestaCell ®
Additional relevant MeSH terms:
Huntington Disease

Study Results

No Results Posted as of Oct 24, 2023