Huntington DiseasePhase 2/3ADORE-EXTNCT04219241
Clinical Extension Study for Safety and Efficacy Evaluation of Cellavita-HD Administration in Huntington's Patients.
A Phase 2/3 study testing Cellavita-HD in people with Huntington Disease, run by Azidus Brasil at 1 site in Brazil.
Trial summary
Cellavita-HD is a stem-cell therapy for Huntington's Disease. Open label, single treatment, extension study for long-term safety and efficacy evaluation of Cellavita-HD intravenous administration in Huntington's disease patients who participated of ADORE-DH trial. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Huntington Disease
- What is being tested?
- Cellavita-HD
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteBrazil
- Study dates
- 10 Feb 2020to Dec 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase II study participants (ADORE-DH) who express interest in participating in the extension period and who may have significant clinical benefits (motor, cognitive, behavioral and functional capacity) at the Investigator's judged after intravenous application of the Cellavita-HD product;
- Provide consent by signing in two copies of the Informed Consent Form;
- Participant using an acceptable contraceptive method.
Who cannot join
- History of malignant neoplasia;
- Present any clinical and laboratory condition or comorbidity that, at the physician's judged, may endanger the health of the research participant and prevent him / her from being part of the extension study;
- known hypersensitivity to the investigational product and / or products of bovine origin;
- Research participant who has participated in clinical trial protocols in the last twelve (12) months, unless the Investigator believes that there may be direct benefit to it (Resolution CNS 251 of August 7, 1997, item III, sub-item J);
- Pregnant or lactating participant;
- In use or anticipated use of immunosuppressive drugs as well as any other drug in which the use is restricted to this research protocol.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.
Valinhos, São Paulo, 13271-130
About this study
Official title: Clinical Extension Study for Assessing the Safety and Efficacy of the Intravenous Administration of Cellavita-HD in Huntington's Disease Patients Who Participated in the ADORE-DH Study.
Cellavita-HD is a stem-cell therapy for Huntington's Disease. Open label, single treatment, extension study for long-term safety and efficacy evaluation of Cellavita-HD intravenous administration in Huntington's disease patients who participated of ADORE-DH trial.
Read the detailed description
This extension study will include the subjects who participated the study phase II for dose-response evaluation of Cellavita-HD intravenous administration in Huntington's disease patients (maximum 35 subjects). Because it is a extension study, with an open scenario, the subjects will receive the maximum dose tested in the last clinical trial (ADORE-DH), corresponding to 6 x 10^6 cells/weight range for each treatment cycle planned. Throughout of 24 months, the subjects will receive total dose planned divided into three administrations per cycle (2 x 10^6 cells/weight range), that each will occur every 30 days. The maintaining the effectiveness of intravenous administration of Cellavita-HD product over time on clinical progression Huntington's disease will be verified by comparing the UHDRS total score at the end of the 24th study month against baseline score. Secondary evidences of efficacy will be evaluated by 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
- Being tested
- Cellavita-HD
- Keywords
- Huntington Disease, Stem cell therapy, Dental Pulp Stem Cell
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cellavita-HDBiological
Also called cellular therapy, mesenchymal stem cells
The participants will receive a total of 12 intravenous administrations of 2x10^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 180 days (total of 4 cycles).
| Study group | Role | What they receive |
|---|---|---|
| Cellavita-HD | Experimental | The participants will receive a total of 12 intravenous administrations of 2x10^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 180 days (total of 4 cycles). Receives: Biological: Cellavita-HD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maintenance of effectiveness on clinical progression of the disease
The maintenance of treatment effectiveness will be verified by comparing the total UHDRS (Unified Huntington's Disease Rating Scale) score registered at the end of the 24th month of study in relation to the baseline score.
Measured: Two years (every study visit)
Secondary outcomes (5)
Clinical neurological worsening over the treatment by UHDRS
The clinical neurological worsening over the treatment will be evaluated by specific Unified Huntington's Disease Rating Scale - UHDRS subscales (motor, behavior, functional capacity and cognitive domain). Each specific domain have 4 categories (from 0 to 4). For motor subscale, the score ranged from 0 to 124; Therefore,highest scores indicate more severe motor impairment. Cognitive operations are assessed by aplication of three tests: verbal fluency test, Symbol Digit modalities test and the Stroop Color Word test. For all cognitive tests, highest scores translate to better cognitive ability. Behavior assessment score is obtained by summing different items related to the severity of psychiatric symptoms. Highest scores indicate greater behavioral impairment. Functional assessment includes three scales: a functional checklist, an independence scale, and a total functional capacity assessment. The maximum score of 25 points represents greater functional capacity.
Measured: Two years
BMI assessment
The BMI (Body Mass Index) will be evaluated through the BMI profiles obtained during the treatment to evaluate the nutritional status.
Measured: Two years
Risk of suicidal ideation and/or behavior by C-SSRS
Will be evaluated by Columbia Suicide Severity Rating Scale (C-SSRS) registered throughout the study in relation to the baseline score. The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk. Greater lethality or potential lethality of the behavior (endorsed on the Behavior subscale) indicates increased risk.
Measured: Two years
Risk of suicidal ideation and/or behavior by HDS
Will be evaluated through Suicidal Domain from HDS (Hamilton Depression Scale) registered throughout the study in relation to the baseline score. Scores above 25 points characterize severely ill patients depressed; scores between 18 and 24 points, moderately depressed patients; and scores between 7 and 17 points, patients with mild depression.
Measured: Two years
CNS assessment by MRI (Magnetic Ressonance Imaging)
Huntington's patients normally present MRI structural abnormalities, including cortical atrophy and structural white matter changes. Alterations after product administration will be evaluated througout statistical comparison of the CNS assessment through magnetic resonance imaging at cortical thickness measurements, volumes of different brain structures, especially the basal ganglia, with special attention to caudate and metabolic changes identified in proton spectroscopy.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2020
- Study start10 Feb 2020
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azidus Brasil
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cellavita Pesquisa Científica Ltda
- Responsible party
- Sponsor
- Investigators
- Joyce Macedo, MD, Principal investigator, Azidus Brasil Scientific Research and Development Ltda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04219241
- Sponsor's protocol ID
- ADORE-EXT
- Other IDs
- 23917319.0.0000.5412
- Acronym
- ADORE-EXT
- Status last verified
- Oct 2022
- First submitted
- 11 Dec 2019
- Last updated
- 28 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data will become public.
Publications
Adachi N, Numakawa T, Richards M, Nakajima S, Kunugi H. New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases. World J Biol Chem. 2014 Nov 26;5(4):409-28. doi: 10.4331/wjbc.v5.i4.409.
PubMed 25426265Aleynik 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.
PubMed 25097727Bachoud-Levi AC, Gaura V, Brugieres P, Lefaucheur JP, Boisse MF, Maison P, Baudic S, Ribeiro MJ, Bourdet C, Remy P, Cesaro P, Hantraye P, Peschanski M. Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study. Lancet Neurol. 2006 Apr;5(4):303-9. doi: 10.1016/S1474-4422(06)70381-7.
PubMed 16545746Barker 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.
PubMed 23345280Goldberg YP, Kremer B, Andrew SE, Theilmann J, Graham RK, Squitieri F, Telenius H, Adam S, Sajoo A, Starr E, et al. Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects. Nat Genet. 1993 Oct;5(2):174-9. doi: 10.1038/ng1093-174.
PubMed 8252043Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group. Mov Disord. 1996 Mar;11(2):136-42. doi: 10.1002/mds.870110204.
PubMed 8684382Jia JM, Chen Q, Zhou Y, Miao S, Zheng J, Zhang C, Xiong ZQ. Brain-derived neurotrophic factor-tropomyosin-related kinase B signaling contributes to activity-dependent changes in synaptic proteins. J Biol Chem. 2008 Jul 25;283(30):21242-50. doi: 10.1074/jbc.M800282200. Epub 2008 May 12.
PubMed 18474605Kerkis I, Haddad MS, Valverde CW, Glosman S. Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges. Stem Cell Res Ther. 2015 Dec 14;6:232. doi: 10.1186/s13287-015-0248-1.
PubMed 26667114Marder K, Zhao H, Myers RH, Cudkowicz M, Kayson E, Kieburtz K, Orme C, Paulsen J, Penney JB Jr, Siemers E, Shoulson I. Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology. 2000 Jan 25;54(2):452-8. doi: 10.1212/wnl.54.2.452.
PubMed 10668713
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Extension Study for Assessing the Safety and Efficacy of the Intravenous Administration of Cellavita-HD in Huntington's Disease Patients Who Participated in the ADORE-DH Study.
- ClinicalTrials.gov ID
- NCT04219241
- Acronym / sponsor ID
- ADORE-EXT / ADORE-EXT
- Conditions
- Huntington Disease
- Keywords
- Huntington Disease, Stem cell therapy, Dental Pulp Stem Cell
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Azidus BrasilIndustry (pharma, biotech, devices)
- Collaborators
- Cellavita Pesquisa Científica Ltda
- Study start
- 10 Feb 2020 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 7 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cellavita-HD is a stem-cell therapy for Huntington's Disease. Open label, single treatment, extension study for long-term safety and efficacy evaluation of Cellavita-HD intravenous administration in Huntington's disease patients who participated of ADORE-DH trial.
Detailed description
This extension study will include the subjects who participated the study phase II for dose-response evaluation of Cellavita-HD intravenous administration in Huntington's disease patients (maximum 35 subjects). Because it is a extension study, with an open scenario, the subjects will receive the maximum dose tested in the last clinical trial (ADORE-DH), corresponding to 6 x 10^6 cells/weight range for each treatment cycle planned. Throughout of 24 months, the subjects will receive total dose planned divided into three administrations per cycle (2 x 10^6 cells/weight range), that each will occur every 30 days. The maintaining the effectiveness of intravenous administration of Cellavita-HD product over time on clinical progression Huntington's disease will be verified by comparing the UHDRS total score at the end of the 24th study month against baseline score. Secondary evidences of efficacy will be evaluated by 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cellavita-HD | Experimental | Biological: Cellavita-HDThe participants will receive a total of 12 intravenous administrations of 2x10^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 180 days (total of 4 cycles). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Phase II study participants (ADORE-DH) who express interest in participating in the extension period and who may have significant clinical benefits (motor, cognitive, behavioral and functional capacity) at the Investigator's judged after intravenous application of the Cellavita-HD product;
- Provide consent by signing in two copies of the Informed Consent Form;
- Participant using an acceptable contraceptive method.
Key exclusion criteria (6 listed)
- History of malignant neoplasia;
- Present any clinical and laboratory condition or comorbidity that, at the physician's judged, may endanger the health of the research participant and prevent him / her from being part of the extension study;
- known hypersensitivity to the investigational product and / or products of bovine origin;
- Research participant who has participated in clinical trial protocols in the last twelve (12) months, unless the Investigator believes that there may be direct benefit to it (Resolution CNS 251 of August 7, 1997, item III, sub-item J);
- Pregnant or lactating participant;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cellavita-HDAlso: cellular therapy, mesenchymal stem cellsThe participants will receive a total of 12 intravenous administrations of 2x10^6 cells/weight range divided into three administrations per cycle. Each administration will occur every 30 days and cycles every 180 days (total of 4 cycles). | Biological | Cellavita-HD |
Primary outcome
Maintenance of effectiveness on clinical progression of the disease
Time frame: Two years (every study visit)
The maintenance of treatment effectiveness will be verified by comparing the total UHDRS (Unified Huntington's Disease Rating Scale) score registered at the end of the 24th month of study in relation to the baseline score.
5 secondary outcomes
Clinical neurological worsening over the treatment by UHDRS
Time frame: Two years
BMI assessment
Time frame: Two years
Risk of suicidal ideation and/or behavior by C-SSRS
Time frame: Two years
Risk of suicidal ideation and/or behavior by HDS
Time frame: Two years
CNS assessment by MRI (Magnetic Ressonance Imaging)
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
- Background: PubMed 25426265Adachi N, Numakawa T, Richards M, Nakajima S, Kunugi H. New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases. World J Biol Chem. 2014 Nov 26;5(4):409-28. doi: 10.4331/wjbc.v5.i4.409.
- Background: PubMed 25097727Aleynik 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.
- Background: PubMed 16545746Bachoud-Levi AC, Gaura V, Brugieres P, Lefaucheur JP, Boisse MF, Maison P, Baudic S, Ribeiro MJ, Bourdet C, Remy P, Cesaro P, Hantraye P, Peschanski M. Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study. Lancet Neurol. 2006 Apr;5(4):303-9. doi: 10.1016/S1474-4422(06)70381-7.
- Background: PubMed 23345280Barker 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.
- Background: PubMed 8252043Goldberg YP, Kremer B, Andrew SE, Theilmann J, Graham RK, Squitieri F, Telenius H, Adam S, Sajoo A, Starr E, et al. Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects. Nat Genet. 1993 Oct;5(2):174-9. doi: 10.1038/ng1093-174.
- Background: PubMed 8684382Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group. Mov Disord. 1996 Mar;11(2):136-42. doi: 10.1002/mds.870110204.
- Background: PubMed 18474605Jia JM, Chen Q, Zhou Y, Miao S, Zheng J, Zhang C, Xiong ZQ. Brain-derived neurotrophic factor-tropomyosin-related kinase B signaling contributes to activity-dependent changes in synaptic proteins. J Biol Chem. 2008 Jul 25;283(30):21242-50. doi: 10.1074/jbc.M800282200. Epub 2008 May 12.
- Background: PubMed 26667114Kerkis I, Haddad MS, Valverde CW, Glosman S. Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges. Stem Cell Res Ther. 2015 Dec 14;6:232. doi: 10.1186/s13287-015-0248-1.
- Background: PubMed 10668713Marder K, Zhao H, Myers RH, Cudkowicz M, Kayson E, Kieburtz K, Orme C, Paulsen J, Penney JB Jr, Siemers E, Shoulson I. Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology. 2000 Jan 25;54(2):452-8. doi: 10.1212/wnl.54.2.452.
- Individual participant dataSharing planned: Undecided. It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data will become public.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joyce Macedo, MD principal investigator
Azidus Brasil Scientific Research and Development Ltda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Cellavita-HD in people with Huntington Disease, run by Azidus Brasil at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maintenance of effectiveness on clinical progression of the disease (time frame: Two years (every study visit)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04219241, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2022.