Dose-response Evaluation of the Cellavita HD Product in Patients With Huntington's Disease

NCT03252535 | Completed Phase 2 Results

• 2 other identifiers: ADORE-DH52375916.1.0000.5412
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Cellavita HD is a stem-cell therapy for Huntington's Disease. This is a prospective, phase II, single-center, randomized (2:2:1), triple-blind, placebo controlled study, with two test doses of Cellavita HD product.

Conditions

Huntington Disease

Keywords

Huntington disease; Stem cell therapy; Dental pulp stem cell

Outcome Measures

Primary Outcomes (1)

• Efficacy by UHDRS-TMS

  The primary endpoint was the rate of change (slope) in Unified Huntington's Disease Rating Scale - Total Motor Score from V0 to V11 (minimum 0, the best; and maximum 124, the worst). For each participant, a regression line was fitted (Y = a + bx), where b represents the individual slope, reflecting the annualised rate of motor progression. A negative slope suggests improvement or slower decline; a positive slope indicates worsening. To compare treatment efficacy, the slopes were analysed using a Mixed Model for Repeated Measures (MMRM), which accounts for intra-subject variability and missing data. This approach allowed estimation and comparison of average slopes between each treated group and placebo, providing a robust measure of motor function trajectory over time.

  monthly for eleven months

Secondary Outcomes (1)

• Efficacy by UHDRS-TFC

  monthly for eleven months

Other Outcomes (1)

• Exposure to NestaCell (Former Cellavita HD) Product

  eleven months

Study Arms (3)

Cellavita HD Lower Dose

EXPERIMENTAL

The participants randomized to this group will receive a total of 9 intravenous administrations of 1x10\^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Biological: Cellavita HD lower dose

Cellavita HD Higher Dose

EXPERIMENTAL

The participants randomized to this group will receive a total of 9 intravenous administrations of 2x10\^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Biological: Cellavita HD higher dose

Placebo Group

PLACEBO COMPARATOR

The participants randomized to this group will receive a total of 9 intravenous administrations divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Other: Placebo

Interventions

Cellavita HD lower dose BIOLOGICAL

The participants will receive a total of 9 intravenous administrations of 1x10\^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Also known as: cellular therapy, mesenchymal stem cells

Cellavita HD Lower Dose

Cellavita HD higher dose BIOLOGICAL

The participants will receive a total of 9 intravenous administrations of 2x10\^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Also known as: cellular therapy, mesenchymal stem cells

Cellavita HD Higher Dose

Placebo OTHER

The participants will receive a total of 9 intravenous administrations of placebo divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 120 days (total of 3 cycles).

Also known as: physiological solution without cells

Placebo Group

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide a written, signed and dated Informed Consent Form;
• Male and female subjects aged ≥ 21 and ≤ 65 years;
• Have a confirmatory diagnosis report (PCR) of Huntington's disease with a number of CAG repeats in chromosome 4 higher than or equal to 40, and lower than or equal to 50 (if the subject did not perform the exam and/or if he/she does not have an available result for this exam, a new exam must be performed);
• A score of 5 points or higher for the motor evaluation of the UHDRS scale (Unified Huntington's Disease Rating Scale) at enrollment;
• Score of 8 to 11 points for the functional capacity of the UHDRS scale at enrollment.

You may not qualify if:

• Subject who participated in clinical trials protocols within the last twelve (12) months (Resolution CNS 251, August 7, 1997, item III, subitem J), unless, at the investigator's opinion, the subject would have a direct benefit from it;
• Diagnosis of juvenile Huntington's disease;
• Diagnosis of epilepsy;
• Diagnosis of major cognitive disorder;
• Active decompensated psychiatric illness;
• Current or prior history of neoplasm;
• Current history of gastrointestinal, hepatic, renal, endocrine, pulmonary, hematological, immunological, metabolic pathology or severe uncontrolled cardiovascular diseases;
• Diagnosis of any active infection, whether viral, bacterial, fungal or caused by another pathogen;
• Subject with contraindication to the exams performed in this study, for example, with pacemaker or surgical clip; Alcohol and drugs abuse (previously diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders - DSM V criteria);
• Use of illegal drugs;
• Tabagism;
• Smoker or quit smoking for less than 6 months;
• Positive result in one of the serum tests: HIV 1 and 2 (Anti-HIV-1,2), HTLV I and II, HBV (HBsAg, Anti-HBc), HCV (anti-HCV-Ab) and FTA-ABS (Treponema pallidum);
• History of drug allergy, including to contrast agents used in imaging tests or bovine-derived products;
• Using or expects to use immunosuppressant drugs or forbidden drugs (item 5.3) during the first three months after the first administration of the investigational product;

Sponsors & Collaborators

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

Study Sites (1)

Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.

Valinhos, São Paulo, 13271-130, Brazil

Location

Related Publications (13)

• Aleynik A, Gernavage KM, Mourad YSh, Sherman LS, Liu K, Gubenko YA, Rameshwar P. Stem cell delivery of therapies for brain disorders. Clin Transl Med. 2014 Jul 19;3:24. doi: 10.1186/2001-1326-3-24. eCollection 2014.

  PMID: 25097727 BACKGROUND

• de Almeida FM, Marques SA, Ramalho Bdos S, Rodrigues RF, Cadilhe DV, Furtado D, Kerkis I, Pereira LV, Rehen SK, Martinez AM. Human dental pulp cells: a new source of cell therapy in a mouse model of compressive spinal cord injury. J Neurotrauma. 2011 Sep;28(9):1939-49. doi: 10.1089/neu.2010.1317. Epub 2011 Aug 8.

  PMID: 21609310 BACKGROUND

• Barker RA, Mason SL, Harrower TP, Swain RA, Ho AK, Sahakian BJ, Mathur R, Elneil S, Thornton S, Hurrelbrink C, Armstrong RJ, Tyers P, Smith E, Carpenter A, Piccini P, Tai YF, Brooks DJ, Pavese N, Watts C, Pickard JD, Rosser AE, Dunnett SB; NEST-UK collaboration. The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease. J Neurol Neurosurg Psychiatry. 2013 Jun;84(6):657-65. doi: 10.1136/jnnp-2012-302441. Epub 2013 Jan 23.

  PMID: 23345280 BACKGROUND

• Bonelli RM, Wenning GK. Pharmacological management of Huntington's disease: an evidence-based review. Curr Pharm Des. 2006;12(21):2701-20. doi: 10.2174/138161206777698693.

  PMID: 16842168 BACKGROUND

• de Souza PV, Alves FB, Costa Ayub CL, de Miranda Soares MA, Gomes JR. Human immature dental pulp stem cells (hIDPSCs), their application to cell therapy and bioengineering: an analysis by systematic revision of the last decade of literature. Anat Rec (Hoboken). 2013 Dec;296(12):1923-8. doi: 10.1002/ar.22808. Epub 2013 Oct 15.

  PMID: 24130093 BACKGROUND

• Fink KD, Deng P, Torrest A, Stewart H, Pollock K, Gruenloh W, Annett G, Tempkin T, Wheelock V, Nolta JA. Developing stem cell therapies for juvenile and adult-onset Huntington's disease. Regen Med. 2015;10(5):623-46. doi: 10.2217/rme.15.25.

  PMID: 26237705 BACKGROUND

• Kerkis I, Caplan AI. Stem cells in dental pulp of deciduous teeth. Tissue Eng Part B Rev. 2012 Apr;18(2):129-38. doi: 10.1089/ten.TEB.2011.0327. Epub 2011 Dec 28.

  PMID: 22032258 BACKGROUND

• Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, Scahill RI, Leavitt BR, Stout JC, Paulsen JS, Reilmann R, Unschuld PG, Wexler A, Margolis RL, Tabrizi SJ. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014 Apr;10(4):204-16. doi: 10.1038/nrneurol.2014.24. Epub 2014 Mar 11.

  PMID: 24614516 BACKGROUND

• Kaplan A, Stockwell BR. Therapeutic approaches to preventing cell death in Huntington disease. Prog Neurobiol. 2012 Dec;99(3):262-80. doi: 10.1016/j.pneurobio.2012.08.004. Epub 2012 Aug 28.

  PMID: 22967354 BACKGROUND

• Weiss A, Trager U, Wild EJ, Grueninger S, Farmer R, Landles C, Scahill RI, Lahiri N, Haider S, Macdonald D, Frost C, Bates GP, Bilbe G, Kuhn R, Andre R, Tabrizi SJ. Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression. J Clin Invest. 2012 Oct;122(10):3731-6. doi: 10.1172/JCI64565. Epub 2012 Sep 17.

  PMID: 22996692 BACKGROUND

• Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR; International Huntington's Disease Collaborative Group. A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length. Clin Genet. 2004 Apr;65(4):267-77. doi: 10.1111/j.1399-0004.2004.00241.x.

  PMID: 15025718 BACKGROUND

• Fernandes JMS, Pagani E, Wenceslau CV, Ynoue LH, Ferrara L, Kerkis I. Phase II trial of intravenous human dental pulp stem cell therapy for Huntington's disease: a randomized, double-blind, placebo-controlled study. Stem Cell Res Ther. 2025 Aug 6;16(1):432. doi: 10.1186/s13287-025-04557-2.

  PMID: 40770775 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

Cell- and Tissue-Based Therapy; Cell Count

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

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Results Point of Contact

• Title: Cristiane Valverde Wenceslau
• Organization: Cellavita

cristiane.valverde@cellavitabrasil.com.br

+55 (19) 3829.0849

Study Officials

• Joyce Macedo da Silva, MD

  Azidus Brasil Scientific Research and Development Ltda

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study drugs will be provided in identical packages to maintain the study masking. Neither the Investigator nor the study team will know which drug the subject is receiving. In addition, the external outcome evaluator will receive the results in a codified manner (concealed).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2017
• First Posted: August 17, 2017
• Study Start: January 15, 2018
• Primary Completion: March 23, 2021
• Study Completion: April 30, 2021
• Last Updated: September 19, 2025
• Results First Posted: September 19, 2025

Record last verified: 2025-09

Locations

BR (1)