Efficacy and Safety of NestaCell® in Huntington's Disease

NCT06097780 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: STARU1111-1298-5627
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Huntington Disease

Keywords

STAR; NestaCell ®

Outcome Measures

Primary Outcomes (1)

• Primary Efficacy Objective

  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 Outcomes (9)

• Secondary Efficacy Objectives

  1 year

• Secondary Efficacy Objectives

  1 year

• Secondary Efficacy Objectives

  1 year

• Secondary Efficacy Objectives

  1 year

• Secondary Efficacy Objectives

  1 year

Other Outcomes (7)

• Secondary Safety Objective

  1 year

• Exploratory objectives

  1 year

• Exploratory objectives

  Up to 9 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Arm 1: Nine intravenous placebo administrations in twelve months.

Genetic: NestaCell®

Intravenous NestaCell® administrations

EXPERIMENTAL

Arm 2: Nine intravenous NestaCell® administrations in twelve months.

Genetic: NestaCell®

Interventions

NestaCell® GENETIC

Human Dental Pulp Stem Cells (hDPSCs).

Intravenous NestaCell® administrations; Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Azidus Brasil: lead
• Cellavita Pesquisa Científica Ltda: collaborator

Related Publications (24)

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  BACKGROUND

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• Benedict RH, DeLuca J, Phillips G, LaRocca N, Hudson LD, Rudick R; Multiple Sclerosis Outcome Assessments Consortium. Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Mult Scler. 2017 Apr;23(5):721-733. doi: 10.1177/1352458517690821. Epub 2017 Feb 16.

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• BENTON, A. L.; HAMSHER, K. S.; SIVAN, A. B.; PSYCHOLOGICAL ASSESSMENT RESOURCES, I. Multilingual Aphasia Examination, Third Edition: Manual of instructions. PAR, 1978.

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• Biglan KM, Zhang Y, Long JD, Geschwind M, Kang GA, Killoran A, Lu W, McCusker E, Mills JA, Raymond LA, Testa C, Wojcieszek J, Paulsen JS; PREDICT-HD Investigators of the Huntington Study Group. Refining the diagnosis of Huntington disease: the PREDICT-HD study. Front Aging Neurosci. 2013 Apr 2;5:12. doi: 10.3389/fnagi.2013.00012. eCollection 2013.

  PMID: 23565093 BACKGROUND

• Chen J, Marks E, Lai B, Zhang Z, Duce JA, Lam LQ, Volitakis I, Bush AI, Hersch S, Fox JH. Iron accumulates in Huntington's disease neurons: protection by deferoxamine. PLoS One. 2013 Oct 11;8(10):e77023. doi: 10.1371/journal.pone.0077023. eCollection 2013.

  PMID: 24146952 BACKGROUND

• Dorsey ER, Beck CA, Darwin K, Nichols P, Brocht AF, Biglan KM, Shoulson I; Huntington Study Group COHORT Investigators. Natural history of Huntington disease. JAMA Neurol. 2013 Dec;70(12):1520-30. doi: 10.1001/jamaneurol.2013.4408.

  PMID: 24126537 BACKGROUND

• FDA. Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products. pp. 27.

  BACKGROUND

• Frank S, Testa C, Edmondson MC, Goldstein J, Kayson E, Leavitt BR, Oakes D, O'Neill C, Vaughan C, Whaley J, Gross N, Gordon MF, Savola JM; Huntington Study Group/ARC-HD Investigators and Coordinators. The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study. CNS Drugs. 2022 Nov;36(11):1207-1216. doi: 10.1007/s40263-022-00956-8. Epub 2022 Oct 15.

  PMID: 36242718 BACKGROUND

• GAMARRA, L.; CINTRA, L.; GÁRATE, A. P. Relatório Final do Estudo de Biodistribuição do Produto NestaCell®. Centro de Experimentação e Treinamento em Cirurgia (CETEC) do Instituto Israelita de Ensino e Pesquisa Hospital Albert Einstein, p. 72. 2022.

  BACKGROUND

• Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group. Mov Disord. 1996 Mar;11(2):136-42. doi: 10.1002/mds.870110204.

  PMID: 8684382 BACKGROUND

• JANUÁRIO, C. Doença de Huntington. Onde estamos agora? 2011. 148 f. (Doutor) -, Universidade de Coimbra.

  BACKGROUND

• Muller M, Leavitt BR. Iron dysregulation in Huntington's disease. J Neurochem. 2014 Aug;130(3):328-50. doi: 10.1111/jnc.12739. Epub 2014 May 28.

  PMID: 24717009 BACKGROUND

• Niu L, Ye C, Sun Y, Peng T, Yang S, Wang W, Li H. Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington's disease. Cell Biosci. 2018 Jul 4;8:41. doi: 10.1186/s13578-018-0239-x. eCollection 2018.

  PMID: 30002810 BACKGROUND

• PATTERSON, J. Verbal Fluency. In: KREUTZER, J. S.;DELUCA, J., et al (Ed.). Encyclopedia of Clinical Neuropsychology. New York, NY: Springer New York, 2011. p. 2603-2606.

  BACKGROUND

• Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington's disease: a systematic review and meta-analysis. Mov Disord. 2012 Aug;27(9):1083-91. doi: 10.1002/mds.25075. Epub 2012 Jun 12.

  PMID: 22692795 BACKGROUND

• Resolução CNS nº 466. Brasília: Conselho Nacional de Saúde 2012.

  BACKGROUND

• Resolução RDC n°508. Brasilia: Conselho Nacional de Saúde 2021.

  BACKGROUND

• SPREEN, O.; SPREEN, B. P. P. O.; STRAUSS, E.; STRAUSS, P. P. E. A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary. Oxford University Press, USA, 1998. 9780195100198.

  BACKGROUND

• Tumas V, Camargos ST, Jalali PS, Galesso Ade P, Marques W Jr. Internal consistency of a Brazilian version of the unified Huntington's disease rating scale. Arq Neuropsiquiatr. 2004 Dec;62(4):977-82. doi: 10.1590/S0004-282X2004000600009. Epub 2004 Dec 15.

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  PMID: 17240289 BACKGROUND

• Wenceslau CV, de Souza DM, Mambelli-Lisboa NC, Ynoue LH, Araldi RP, da Silva JM, Pagani E, Haddad MS, Kerkis I. Restoration of BDNF, DARPP32, and D2R Expression Following Intravenous Infusion of Human Immature Dental Pulp Stem Cells in Huntington's Disease 3-NP Rat Model. Cells. 2022 May 17;11(10):1664. doi: 10.3390/cells11101664.

  PMID: 35626701 BACKGROUND

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Luciana Ferrara, Doctor

  Azidus Brasil

  STUDY DIRECTOR

Central Study Contacts

Luciana Ferrara, Doctor

CONTACT

+ 55 19 981428814; luciana.ferrara@azidusbrasil.com.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The trial will be two-armed double-blind (participant and investigator's team responsible for outcome assessments).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 24, 2023
• Study Start: June 8, 2024
• Primary Completion: September 8, 2025
• Study Completion: February 9, 2026
• Last Updated: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share