Sanfilippo Syndrome BPhase 1/2NCT03300453
Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome
A Phase 1/2 study testing rAAV2/5-hNAGLU in people with Sanfilippo Syndrome B, run by UniQure Biopharma B.V. at 1 site in France.
Trial summary
This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome. Read more about this study
- Who is it for?
- Ages 18 to 60 months
- Conditions the study is for
- Sanfilippo Syndrome B
- What is being tested?
- rAAV2/5-hNAGLU
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteFrance
- Study dates
- 17 Sep 2013to 27 Nov 2019
- Phase
- Phase 1/2
- 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 18 to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age: 18 months up to 60 months (5th birthday);
- Onset of clinical manifestations related to mucopolysaccharidosis type IIIB (MPSIIIB);
- NAGLU activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls;
- Patient affiliated to, or covered by a French social security regimen, or European patients with European Health Insurance Card;
- Family understanding the procedure and the informed consent;
- Signed informed consent by both parents or legal representative;
- Vital laboratory parameters within normal range.
Who cannot join
- Presence of brain atrophy on baseline MRI judged on a cortico-dural distance of more than 0.6 cm;
- Any condition that would contraindicate general anesthesia;
- Any other permanent medical condition not related to MPSIIIB that could contraindicate the study participation;
- No independent walking (ability to walk without help);
- Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection (sleep and mood regulators are accepted);
- Any condition that would contraindicate treatment with Modigraf®, Cellcept® and prednisolone (Solupred® and Solumedrol®).
Trial locations and contacts
1 site in 1 country.
France1 site
Hopitaux Universitaires Paris-Sud
Paris, Le Kremlin-Bicetre Cedex, 94275
About this study
Official title: Protocol AMT110-CD-001: A Phase I/II, Open-label, Study of Intracerebral Administration of Adeno-associated Viral Vector Containing the Human Alpha-N-acetylglucosaminidase cDNA in Children With Sanfilippo Type B Syndrome
This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.
Read the detailed description
This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.
Four patients, 18 months up to the 5th birthday, have been included.
The inclusion period will be 8 to 12 months. The duration of follow-up for each patient is 1 year post-surgery. The duration of the first extension phase is 18 months. The duration of the second extension phase is 36 months. Therefore, the maximum time of the follow-up will be 66 months
- Conditions
- Sanfilippo Syndrome B
- Being tested
- rAAV2/5-hNAGLU
- Medical subject headings
- Mucopolysaccharidosis III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV2/5-hNAGLUDrug
Also called AAV5
one-time brain intraparenchymal gene therapy dose
| Study group | Role | What they receive |
|---|---|---|
| rAAV2/5-hNAGLU | Experimental | Each patient will receive 960 µL of vector suspension. The vector suspension will be deposited simultaneously at 16 sites, each deposit containing 2.4x 1011 vg (4x1012 vg in total). Receives: Drug: rAAV2/5-hNAGLU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline
Multiple measurements will be aggregated to derive the number of participants with Abnormal Laboratory Values and/or Adverse Events that are related to Treatment.
Measured: Baseline until end of study (Month 66)
Secondary outcomes (1)
Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI
MRIs at Baseline, Month 3, Month 12, Month 30, Month 48 and last visit Month 66.
Cerebral MRI will be collected for safety assessment to retrospectively evaluate for efficacy at Baseline, D0, Month 3, Month12, Month 30 and last visit Month 66.
Measured: Baseline until end of study (Month 66)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start17 Sep 2013
- Primary completion27 Nov 2019
- Study completion27 Nov 2019
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 Sanfilippo Syndrome BStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- UniQure Biopharma B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Venn Life Sciences, Institut Pasteur
- Responsible party
- Sponsor
- Investigators
- Kumaran Deiva, MD, Principal investigator, Hopitaux Universitaires Paris-Sud
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03300453
- Sponsor's protocol ID
- AMT110-CD-001
- Status last verified
- Oct 2018
- First submitted
- 15 Jun 2016
- Last updated
- 2 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gougeon ML, Poirier-Beaudouin B, Ausseil J, Zerah M, Artaud C, Heard JM, Deiva K, Tardieu M. Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome. Front Immunol. 2021 May 10;12:655478. doi: 10.3389/fimmu.2021.655478. eCollection 2021.
PubMed 34040605
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol AMT110-CD-001: A Phase I/II, Open-label, Study of Intracerebral Administration of Adeno-associated Viral Vector Containing the Human Alpha-N-acetylglucosaminidase cDNA in Children With Sanfilippo Type B Syndrome
- ClinicalTrials.gov ID
- NCT03300453
- Acronym / sponsor ID
- AMT110-CD-001
- Conditions
- Sanfilippo Syndrome B
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- UniQure Biopharma B.V.Industry (pharma, biotech, devices)
- Collaborators
- Venn Life Sciences, Institut Pasteur
- Study start
- 17 Sep 2013 (actual)
- Primary completion
- 27 Nov 2019 (actual)
- Study completion
- 27 Nov 2019 (actual)
- First posted
- 3 Oct 2017 (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.
This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.
Detailed description
This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.
Four patients, 18 months up to the 5th birthday, have been included.
The inclusion period will be 8 to 12 months. The duration of follow-up for each patient is 1 year post-surgery. The duration of the first extension phase is 18 months. The duration of the second extension phase is 36 months. Therefore, the maximum time of the follow-up will be 66 months
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rAAV2/5-hNAGLU | Experimental | Drug: rAAV2/5-hNAGLUEach patient will receive 960 µL of vector suspension. The vector suspension will be deposited simultaneously at 16 sites, each deposit containing 2.4x 1011 vg (4x1012 vg in total). |
Who may qualify
- Ages
- 18 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Age: 18 months up to 60 months (5th birthday);
- Onset of clinical manifestations related to mucopolysaccharidosis type IIIB (MPSIIIB);
- NAGLU activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls;
- Patient affiliated to, or covered by a French social security regimen, or European patients with European Health Insurance Card;
- Family understanding the procedure and the informed consent;
Key exclusion criteria (6 listed)
- Presence of brain atrophy on baseline MRI judged on a cortico-dural distance of more than 0.6 cm;
- Any condition that would contraindicate general anesthesia;
- Any other permanent medical condition not related to MPSIIIB that could contraindicate the study participation;
- No independent walking (ability to walk without help);
- Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection (sleep and mood regulators are accepted);
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 |
|---|---|---|
| rAAV2/5-hNAGLUAlso: AAV5one-time brain intraparenchymal gene therapy dose | Drug | rAAV2/5-hNAGLU |
Primary outcome
Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline
Time frame: Baseline until end of study (Month 66)
Multiple measurements will be aggregated to derive the number of participants with Abnormal Laboratory Values and/or Adverse Events that are related to Treatment.
1 secondary outcome
Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI
Time frame: Baseline until end of study (Month 66)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2019.
- Derived from this study: PubMed 34040605Gougeon ML, Poirier-Beaudouin B, Ausseil J, Zerah M, Artaud C, Heard JM, Deiva K, Tardieu M. Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome. Front Immunol. 2021 May 10;12:655478. doi: 10.3389/fimmu.2021.655478. eCollection 2021.
Related trials for Sanfilippo Syndrome B
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A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)
Mucopolysaccharidosis IIIB
Not yet recruitingPhase 3
Intracerebroventricular Tralesinidase Alfa in Participants With MPS IIIB (Sanfilippo Syndrome Type B)
MPS IIIB
Not yet recruitingPhase 1/2
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Enrolling by invitationObservational study
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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.
Kumaran Deiva, MD principal investigator
Hopitaux Universitaires Paris-Sud
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rAAV2/5-hNAGLU in people with Sanfilippo Syndrome B, run by UniQure Biopharma B.V. at 1 site in France.
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 7 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: finished, as of the sponsor's last update on 2 Dec 2019. 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 France. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline (time frame: Baseline until end of study (Month 66)). 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 NCT03300453, 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 2 Dec 2019.