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

NCT ID: NCT03252535

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-15
• Study Completion Date: 2021-04-30

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.

Detailed Description

This is a phase II dose-response study in which participants with HD will receive three intravenous injections of the investigational product or placebo (one every month for three months) a total of three cycles. The subjects will be randomized in 2: 2: 1 ratio for the groups G1: lower dose (1x10^6 cells/weight range), G2: higher dose (2x10^6 cells/weight range) or G3: placebo. To identify the dose of the product that will provide the best clinical response, motor assessment will be performed with UHDRS scale and improvement will be evaluated by correlating before and after treatment scores. Additionally, also will be performed the combined score through the cUHDRS. Secondary evidences of efficacy will be evaluated through the data of functional state, total functional capacity, functional independence, psychiatric symptoms and cognition from UHDRS scale. Additionally, related data to clinical worsening, change of Body Mass Index (BMI), risk of suicide attempt and neurological image improvement will be evaluated. Safety evaluation will included the incidence and classification of the adverse events experienced by the subjects during the study.

Conditions

Huntington Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Cellavita HD Lower Dose

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).

Group Type: EXPERIMENTAL

Cellavita HD lower dose

Intervention Type: 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).

Cellavita HD Higher Dose

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).

Group Type: EXPERIMENTAL

Cellavita HD higher dose

Intervention Type: 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).

Placebo Group

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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).

Interventions

Cellavita HD lower dose

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).

Intervention Type: BIOLOGICAL

Cellavita HD higher dose

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).

Intervention Type: BIOLOGICAL

Placebo

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).

Intervention Type: OTHER

Other Intervention Names

cellular therapy, mesenchymal stem cells; cellular therapy, mesenchymal stem cells; physiological solution without cells

Eligibility Criteria

Inclusion Criteria

1. Provide a written, signed and dated Informed Consent Form;

2. Male and female subjects aged ≥ 21 and ≤ 65 years;

3. 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);

4. A score of 5 points or higher for the motor evaluation of the UHDRS scale (Unified Huntington's Disease Rating Scale) at enrollment;

5. Score of 8 to 11 points for the functional capacity of the UHDRS scale at enrollment.

Exclusion Criteria

1. 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;

2. Diagnosis of juvenile Huntington's disease;

3. Diagnosis of epilepsy;

4. Diagnosis of major cognitive disorder;

5. Active decompensated psychiatric illness;

6. Current or prior history of neoplasm;

7. Current history of gastrointestinal, hepatic, renal, endocrine, pulmonary, hematological, immunological, metabolic pathology or severe uncontrolled cardiovascular diseases;

8. Diagnosis of any active infection, whether viral, bacterial, fungal or caused by another pathogen;

9. 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);

10. Use of illegal drugs;

11. Tabagism;

12. Smoker or quit smoking for less than 6 months;

13. 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);

14. History of drug allergy, including to contrast agents used in imaging tests or bovine-derived products;

15. 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;

16. Any clinical change that the investigator considers a risk to subject's enrollment in the study.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cellavita Pesquisa Científica Ltda

OTHER

Sponsor Role: collaborator

Azidus Brasil

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joyce Macedo da Silva, MD

Role: PRINCIPAL_INVESTIGATOR

Azidus Brasil Scientific Research and Development Ltda

Locations

Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.

Valinhos, São Paulo, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 25097727 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21609310 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23345280 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16842168 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24130093 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26237705 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22032258 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24614516 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22967354 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22996692 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15025718 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40770775 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35626701 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

52375916.1.0000.5412

Identifier Type: OTHER

Identifier Source: secondary_id

ADORE-DH

Identifier Type: -

Identifier Source: org_study_id