Mucopolysaccharidosis Type IIIAPhase 2/3AAVanceNCT03612869
Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA)
A Phase 2/3 study testing LYS-SAF302 in people with Mucopolysaccharidosis Type IIIA, run by LYSOGENE at 8 sites in 5 countries.
Trial summary
MPS IIIA is predominantly a central nervous system disease causing cognitive disability, progressive loss of acquired skills, behavioral and sleep disturbance. LYS-SAF302 is a gene therapy which is intended to deliver a functional copy of the SGSH gene to the brain. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Mucopolysaccharidosis Type IIIA
- What is being tested?
- LYS-SAF302
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 8 sitesin 5 countries
- Study dates
- 17 Dec 2018to Mar 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
- Cognitive DQ score on BSID-III: 50% and above
Who cannot join
- Homozygous for the S298P mutation or non-classical severe form of MPS IIIA, based on investigator's judgement.
- Participation in another gene or cell therapy clinical trial.
- Past use of SGSH enzyme replacement therapy for a period exceeding 3 months. A washout period of at least 2 months is required prior to screening.
- Current participation in a clinical trial of another investigational medicinal product.
- History of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following surgery.
- Any condition that would contraindicate treatment with immunosuppressants such as tacrolimus, mycophenolate mofetil or steroids.
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
United States4 sites
Baylor college of medicine / Texas children's hospital
Houston, Texas, 77030
University of Minnesota
Minneapolis, Minnesota, 55455
Weill Cornell Medical College
New York, New York, 10065-4897
CHOC Children's
Orange, California, 92868
About this study
Official title: Open-label, Single-arm, Multi-center Study of Intracerebral Administration of Adeno-associated Viral (AAV) Serotype rh.10 Carrying Human N-sulfoglucosamine Sulfohydrolase (SGSH) cDNA for Treatment of Mucopolysaccharidosis Type IIIA
MPS IIIA is predominantly a central nervous system disease causing cognitive disability, progressive loss of acquired skills, behavioral and sleep disturbance. LYS-SAF302 is a gene therapy which is intended to deliver a functional copy of the SGSH gene to the brain. This is a phase 2-3 study to assess the efficacy in improving or stabilizing the neurodevelopmental state of MPS IIIA patients.
Read the detailed description
The study is interventional, single arm and multi-center. Evolution under treatment will be compared to expected natural evolution based on natural history studies.
- Conditions
- Mucopolysaccharidosis Type IIIA
- Being tested
- LYS-SAF302
- Keywords
- MPS IIIA, Sanfilippo syndrome Type A, Mucopolysaccharidosis Type IIIA, Lysosomal Storage Disease
- Medical subject headings
- Mucopolysaccharidosis III, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LYS-SAF302Drug
Also called AAVrh10-h.SGSH
Treatment will involve direct injections of the investigational product into both sides of the brain through image-guided tracks, in a single neurosurgical session.
| Study group | Role | What they receive |
|---|---|---|
| AAV SGSH gene therapy (LYS-SAF302) | Experimental | One-time intracerebral administration of adeno-associated viral vector serotype rh10 containing the human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA. Receives: Drug: LYS-SAF302 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in development quotient (DQ), compared to regression reported in natural history studies
Development Quotient will be measured for each patient using one of two standard instruments, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II), based on age and ability range. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which is computed as a ratio and expressed as a percentage using the development age (DA) score divided by the age at testing ([development age score/chronological age] × 100; range: 0 - 100, where high values are desirable).
Measured: Month 6, 12, 18, 24
Secondary outcomes (6)
Change from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II)
The Vineland Adaptive Behavior Scales VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. The VABS-II is a norm-based instrument, where the child's adaptive functioning is compared to that of others his or her age. The total adaptive behavior composite score describe the child's functioning. The normative mean score is 100 (normative standard deviation is 15). Higher scores indicate better functioning.
Measured: Month 6, 12, 18, 24
Change in sleep pattern as measured by the Childrens Sleep Habits Questionnaire (CSHQ)
The Children's Sleep habits Questionnaire (CSHQ) measures sleep habits and behavioral sleep disorders in preschool and school-aged children. The abbreviated CSHQ is a 23-item multiple-choice questionnaire that is summed into 8 subscales (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night waking, parasomnias, sleep-disordered breathing, and daytime sleepiness) and a CSHQ total score, where higher scores reflect greater disturbance in sleep pattern. Scores will be compared to scores from the Natural History control group, using the same tool and same timepoints.
Measured: Month 6, 12, 18, 24
Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire
The 47-item ITQOL questionnaire assesses physical, mental, and social well-being of the child and the quality of life of parent/caregiver. Scores range from 0 to 100, where higher scores reflect better quality of life. Change in score from baseline will be compared to scores from the Natural History control group, using the same tool and same timepoints.
Measured: Month 12, 24
Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)
The 36-item questionnaire (PSI-4) is used to identify parent-child problem areas, measuring 3 main domains (parental distress, parent-child dysfunctional interaction, and difficult child), which all combined form a total stress score. Higher scores reflect a higher level of stress. Change in score from baseline will be compared to scores from the Natural History control group, using the same tool and same timepoints.
Measured: Month 12, 24
Change from baseline in total cortical grey matter volume and white matter volume on MRI
The change from baseline in grey matter and white matter volume will be assessed by magnetic resonance imaging (MRI)
Measured: Month 12, 24
Incidence and severity of treatment-emergent adverse events and serious adverse events throughout the study
Descriptive summary tables for the surgical period, the evaluation period, and the follow-up period will be provided.
Measured: Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2018
- Study start17 Dec 2018
- Primary completionMar 2022 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mucopolysaccharidosis Type IIIAStudies 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- LYSOGENE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03612869
- Sponsor's protocol ID
- P4-SAF-302
- Acronym
- AAVance
- Status last verified
- Aug 2021
- First submitted
- 4 Jul 2018
- Last updated
- 31 Aug 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tardieu M, Zerah M, Husson B, de Bournonville S, Deiva K, Adamsbaum C, Vincent F, Hocquemiller M, Broissand C, Furlan V, Ballabio A, Fraldi A, Crystal RG, Baugnon T, Roujeau T, Heard JM, Danos O. Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial. Hum Gene Ther. 2014 Jun;25(6):506-16. doi: 10.1089/hum.2013.238. Epub 2014 May 5.
PubMed 24524415
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single-arm, Multi-center Study of Intracerebral Administration of Adeno-associated Viral (AAV) Serotype rh.10 Carrying Human N-sulfoglucosamine Sulfohydrolase (SGSH) cDNA for Treatment of Mucopolysaccharidosis Type IIIA
- ClinicalTrials.gov ID
- NCT03612869
- Acronym / sponsor ID
- AAVance / P4-SAF-302
- Conditions
- Mucopolysaccharidosis Type IIIA
- Keywords
- MPS IIIA, Sanfilippo syndrome Type A, Mucopolysaccharidosis Type IIIA, Lysosomal Storage Disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- LYSOGENEIndustry (pharma, biotech, devices)
- Study start
- 17 Dec 2018 (actual)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 2 Aug 2018 (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.
MPS IIIA is predominantly a central nervous system disease causing cognitive disability, progressive loss of acquired skills, behavioral and sleep disturbance. LYS-SAF302 is a gene therapy which is intended to deliver a functional copy of the SGSH gene to the brain. This is a phase 2-3 study to assess the efficacy in improving or stabilizing the neurodevelopmental state of MPS IIIA patients.
Detailed description
The study is interventional, single arm and multi-center. Evolution under treatment will be compared to expected natural evolution based on natural history studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AAV SGSH gene therapy (LYS-SAF302) | Experimental | Drug: LYS-SAF302One-time intracerebral administration of adeno-associated viral vector serotype rh10 containing the human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
- Cognitive DQ score on BSID-III: 50% and above
Key exclusion criteria (6 listed)
- Homozygous for the S298P mutation or non-classical severe form of MPS IIIA, based on investigator's judgement.
- Participation in another gene or cell therapy clinical trial.
- Past use of SGSH enzyme replacement therapy for a period exceeding 3 months. A washout period of at least 2 months is required prior to screening.
- Current participation in a clinical trial of another investigational medicinal product.
- History of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following surgery.
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 |
|---|---|---|
| LYS-SAF302Also: AAVrh10-h.SGSHTreatment will involve direct injections of the investigational product into both sides of the brain through image-guided tracks, in a single neurosurgical session. | Drug | AAV SGSH gene therapy (LYS-SAF302) |
Primary outcome
Change from baseline in development quotient (DQ), compared to regression reported in natural history studies
Time frame: Month 6, 12, 18, 24
Development Quotient will be measured for each patient using one of two standard instruments, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II), based on age and ability range. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which is computed as a ratio and expressed as a percentage using the development age (DA) score divided by the age at testing ([development age score/chronological age] × 100; range: 0 - 100, where high values are desirable).
6 secondary outcomes
Change from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II)
Time frame: Month 6, 12, 18, 24
Change in sleep pattern as measured by the Childrens Sleep Habits Questionnaire (CSHQ)
Time frame: Month 6, 12, 18, 24
Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire
Time frame: Month 12, 24
Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)
Time frame: Month 12, 24
Change from baseline in total cortical grey matter volume and white matter volume on MRI
Time frame: Month 12, 24
Incidence and severity of treatment-emergent adverse events and serious adverse events throughout the study
Time frame: Month 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2021.
- Background: PubMed 24524415Tardieu M, Zerah M, Husson B, de Bournonville S, Deiva K, Adamsbaum C, Vincent F, Hocquemiller M, Broissand C, Furlan V, Ballabio A, Fraldi A, Crystal RG, Baugnon T, Roujeau T, Heard JM, Danos O. Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial. Hum Gene Ther. 2014 Jun;25(6):506-16. doi: 10.1089/hum.2013.238. Epub 2014 May 5.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing LYS-SAF302 in people with Mucopolysaccharidosis Type IIIA, run by LYSOGENE at 8 sites in 5 countries.
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 2 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 31 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, France, Germany, Netherlands, United Kingdom. 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?
Change from baseline in development quotient (DQ), compared to regression reported in natural history studies (time frame: Month 6, 12, 18, 24). 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 NCT03612869, which also lists 1 linked publication.
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 31 Aug 2021.