Mucopolysaccharidosis Type IIIAPhase 1/2NCT04201405

Gene Therapy with Modified Autologous Hematopoietic Stem Cells for Patients with Mucopolysaccharidosis Type IIIA

A Phase 1/2 study testing Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene in people with Mucopolysaccharidosis Type IIIA, run by University of Manchester at 1 site in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Patients with MPS IIIA have a clinical disorder marked by severe and progressive brain disease and neurological symptoms due to the accumulation of undigested glycosaminoglycans in all cells of the body. Read more about this study

Who is it for?: Ages 3 to 24 months
Conditions the study is for: Mucopolysaccharidosis Type IIIA
What is being tested?: Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited Kingdom
Study dates: 7 Jan 2020to 30 Oct 2026
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

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 3 to 24 months
All sexes
No healthy volunteers
Child

Who may be able to join

Written informed consent of a legally authorized guardian(s)
Age at baseline ≥3 months and ≤24 months
Normal cognitive function or mild cognitive deterioration (subject has a Development Quotient (DQ) score ≥80) at baseline as determined by the Bayley Scale of Infant Development-third edition (BSID-III), cognitive domain)
Sibling or relative of known MPS IIIA patients with rapidly progressing phenotype, or genotype associated with rapidly progressing phenotype, or presence of somatic features predictive of rapid progression
SGSH activity ≤10% of the Lower Limit of Normal as measured in leukocytes, plus either (1) a normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in leukocytes or (2) two documented mutations in the SGSH gene.
Medically stable and able to accommodate the protocol requirements, including travel without placing an undue burden on the patient/patient's family, as determined by the CI.

Who cannot join

The subject has received stem cell, gene therapy or enzyme replacement therapy (any route of administration)
Subject currently enrolled in other interventional clinical trials.
Contraindications for MRI scans.
The subject has a history of poorly controlled seizures.
Homozygous or compound heterozygous for the S298P mutation or any other mutation known to be associated to slow-progressing phenotype.
The subject is currently receiving psychotropic or other medications which, in the CI's opinion, would be likely to substantially confound test results.

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The subject has received any investigational medicinal product (including Genistein) within 30 days prior to the Baseline visit or is scheduled to receive any investigational medicinal product during the course of the study.
Documented Human Immunodeficiency Virus (HIV) infection (positive HIV RNA and/or anti-p24 antibodies).
Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome. Subjects with a prior successfully treated malignancy and a sufficient follow-up to exclude recurrence (based on oncologist opinion) can be included after discussion and approval by the Medical Monitor.
Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukaemia, or other serious haematological disorders.
The subject has a medical condition or extenuating circumstance that, in the opinion of the CI, might compromise the subject's ability to comply with protocol requirements, the subject's well-being or safety, or the interpretability of the subject's clinical data.
Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing.
Severe behavioural disturbances due to reasons other than MPS IIIA and likely to interfere with protocol compliance, as determined by the CI.
Known sensitivity to busulfan.
The receipt of live vaccinations within 30 days prior to study start.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Manchester University NHS Foundation Trust
Manchester, M13 9WL

Other trials in United Kingdom

About this study

Official title: A Phase I-II, Study of Autologous CD34+ Haematopoietic Stem Cells Transduced Ex Vivo with CD11b Lentiviral Vector Encoding for Human SGSH in Patients with Mucopolysaccharidosis Type IIIA (MPS IIIa, Sanfilippo Syndrome Type A)

This study will be the first in human clinical trial to explore the safety, tolerability and clinical efficacy of ex vivo gene therapy (autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene) in MPSIIIA patients. Following treatment with the gene therapy patients will be followed up for a minimum of 3 years.

Read the detailed description

MPS IIIA is caused by a deficiency of the heparan-N-sulfatase (SGSH) enzyme, leading to the accumulation of the glycosaminoglycan heparan sulphate in the lysosomes. Untreated patients of MPS IIIA experience rapid and progressive neurologic deterioration. To date, there is no effective disease-modifying treatment for patients suffering from MPS IIIA.

This study aims to recruit 3 to 5 patients with MPS IIIA who satisfy the inclusion and exclusion criteria and provide full consent, between 3 months and 24 months of age. The investigational medicinal product (IMP) will be a cell-based gene therapy that uses genetically modified autologous CD34+ haematopoietic stem cells transduced with a lentiviral vector containing the human SGSH gene. Patients will be followed up for a minimum of 3 years after gene therapy.

Conditions: Mucopolysaccharidosis Type IIIA
Being tested: Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene
Medical subject headings: Mucopolysaccharidosis III

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH geneDrug
Autologous CD34+ haematopoietic stem cells from MPS IIIA patients will be genetically modified ex vivo using CD11b.SGSH Lentiviral vector (LV), a self-inactivating LV expressing the SGSH gene codon optimized for human use and regulated by a human CD11b myeloid-specific promoter. Cells will be cryopreserved prior to patient administration.

Study groups in NCT04201405
Study group	Role	What they receive
Haematopoietic stem cell gene therapy for MPS IIIA	Experimental	Open label Receives: Drug: Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene

What is being measured

The primary outcome is the main question the study is designed to answer.

To evaluate the tolerability of the IMP in MPS IIIA patients: scale
Adverse events will be recorded and graded according to an adapted Pediatric Clinical Toxicity Scale from the National Institute Allergy and Infectious Diseases (NIAID), Autoimmuno-deficiency Syndrome (AIDS) Division
Measured: up to 3 years
To evaluate the biological efficacy of IMP post-treatment: expression of SGSH in total leukocytes
Measured by the expression of SGSH in total leukocytes within or above normal range at 12 months post-IMP treatment
Measured: 12 months post gene therapy
To assess the safety of the IMP in MPS IIIA patients
Presence of replication competent virus and integration events in the leukocytes
Measured: up to 3 years

Secondary outcomes (7)

To evaluate overall survival
Overall survival at 36 months post IMP administration compared to natural history data
Measured: up to 3 years
To evaluate peripheral engraftment of the IMP
Measured as absence of engraftment failure or delayed hematological reconstitution within the first 6 weeks of IMP delivery. Defined as three independent and consecutive days with absolute Neutrophil Count (ANC) >500/mm3 and/or Platelets >20,000/mm3 without transfusions, and/or Hb >8.0 g/dL without transfusions.
Measured: within 42 days of treatments
Change in adaptive behaviour
Measured using the Vineland Adaptive Behaviour scales against natural history of MPSIIIA
Measured: up to 3 years (multiple visits)
Change in cognitive function
Measurement of cognitive score (standard scores, age equivalent scores and development quotient) using the Bayley Scales of Infant Development, 3rd Edition [BSID-III] or Kaufman Assessment Battery for Children, 2nd Edition [KABC-II] against natural history of MPSIIIA
Measured: up to 3 years (multiple visits)
Change in patient behaviour
Measured using the Sanfilippo Behaviour Rating Scale against natural history of MPSIIIA
Measured: up to 3 years
Change in patient quality of life
Measured using the Infant Toddler Quality of Life questionnaire against natural history of MPSIIIA
Measured: Up to 3 years
Change in patient's daily living
Measured using the Children sleep Questionnaire against natural history data
Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Jan 202030 Oct 2026

First posted17 Dec 2019
Study start7 Jan 2020
Primary completion30 Oct 2024
Study completion30 Oct 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Mucopolysaccharidosis Type IIIAStudies of the same condition, open and under way.
More trials run by University of ManchesterThe sponsor's other registered studies.
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: 5 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04201405
Sponsor's protocol ID: R119861
Status last verified: Mar 2025
First submitted: 5 Dec 2019
Last updated: 30 Mar 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: No, there is not a plan to make IPD available.

Publications

Ellison SM, Liao A, Wood S, Taylor J, Youshani AS, Rowlston S, Parker H, Armant M, Biffi A, Chan L, Farzaneh F, Wynn R, Jones SA, Heal P, Gaspar HB, Bigger BW. Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex Vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA. Mol Ther Methods Clin Dev. 2019 Apr 6;13:399-413. doi: 10.1016/j.omtm.2019.04.001. eCollection 2019 Jun 14.
PubMed 31044143
Holley RJ, Wood SR, Bigger BW. Delivering Hematopoietic Stem Cell Gene Therapy Treatments for Neurological Lysosomal Diseases. ACS Chem Neurosci. 2019 Jan 16;10(1):18-20. doi: 10.1021/acschemneuro.8b00408. Epub 2018 Aug 23.
PubMed 30136572
Ghosh A, Shapiro E, Rust S, Delaney K, Parker S, Shaywitz AJ, Morte A, Bubb G, Cleary M, Bo T, Lavery C, Bigger BW, Jones SA. Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III. Orphanet J Rare Dis. 2017 Jun 26;12(1):117. doi: 10.1186/s13023-017-0675-4.
PubMed 28651568
Sergijenko A, Langford-Smith A, Liao AY, Pickford CE, McDermott J, Nowinski G, Langford-Smith KJ, Merry CL, Jones SA, Wraith JE, Wynn RF, Wilkinson FL, Bigger BW. Myeloid/Microglial driven autologous hematopoietic stem cell gene therapy corrects a neuronopathic lysosomal disease. Mol Ther. 2013 Oct;21(10):1938-49. doi: 10.1038/mt.2013.141. Epub 2013 Jun 7.
PubMed 23748415
Langford-Smith A, Wilkinson FL, Langford-Smith KJ, Holley RJ, Sergijenko A, Howe SJ, Bennett WR, Jones SA, Wraith J, Merry CL, Wynn RF, Bigger BW. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol Ther. 2012 Aug;20(8):1610-21. doi: 10.1038/mt.2012.82. Epub 2012 May 1.
PubMed 22547151

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
Mucopolysaccharidosis Type IIIA
Not yet recruitingObservational study
MPS IIIA Disease Monitoring Program
MPS IIIA, Sanfilippo Syndrome
RecruitingPhase 2/3
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
MPS IIIA, Sanfilippo Syndrome
Not yet recruitingPhase 1/2
Single Injection of rAAV9-CMV-hNAGLUop Gene for Patients With Mucopolysaccharidosis (MPS) IIIB
Sanfilippo Syndrome (MPS III)
Active, not recruitingPhase 1
Phase 1 Study of GC1130A in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo Syndrome Type A

All Mucopolysaccharidosis Type IIIA trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I-II, Study of Autologous CD34+ Haematopoietic Stem Cells Transduced Ex Vivo with CD11b Lentiviral Vector Encoding for Human SGSH in Patients with Mucopolysaccharidosis Type IIIA (MPS IIIa, Sanfilippo Syndrome Type A)
ClinicalTrials.gov ID: NCT04201405
Acronym / sponsor ID: R119861
Conditions: Mucopolysaccharidosis Type IIIA
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 5 participants (estimated)
Lead sponsor: University of ManchesterUniversity, hospital or other
Collaborators: Orchard Therapeutics, CTI Clinical Trial and Consulting Services, University College, London, Great Ormond Street Hospital for Children NHS Foundation Trust, Manchester University NHS Foundation Trust
Study start: 7 Jan 2020 (actual)
Primary completion: 30 Oct 2024 (actual)
Study completion: 30 Oct 2026 (estimated)
First posted: 17 Dec 2019 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Haematopoietic stem cell gene therapy for MPS IIIA	Experimental	Drug: Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH geneOpen label

Who may qualify

Ages: 3 to 24 months
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

Written informed consent of a legally authorized guardian(s)
Age at baseline ≥3 months and ≤24 months
Normal cognitive function or mild cognitive deterioration (subject has a Development Quotient (DQ) score ≥80) at baseline as determined by the Bayley Scale of Infant Development-third edition (BSID-III), cognitive domain)
Sibling or relative of known MPS IIIA patients with rapidly progressing phenotype, or genotype associated with rapidly progressing phenotype, or presence of somatic features predictive of rapid progression
SGSH activity ≤10% of the Lower Limit of Normal as measured in leukocytes, plus either (1) a normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in leukocytes or (2) two documented mutations in the SGSH gene.

Key exclusion criteria (15 listed)

The subject has received stem cell, gene therapy or enzyme replacement therapy (any route of administration)
Subject currently enrolled in other interventional clinical trials.
Contraindications for MRI scans.
The subject has a history of poorly controlled seizures.
Homozygous or compound heterozygous for the S298P mutation or any other mutation known to be associated to slow-progressing phenotype.

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
Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH geneAutologous CD34+ haematopoietic stem cells from MPS IIIA patients will be genetically modified ex vivo using CD11b.SGSH Lentiviral vector (LV), a self-inactivating LV expressing the SGSH gene codon optimized for human use and regulated by a human CD11b myeloid-specific promoter. Cells will be cryopreserved prior to patient administration.	Drug	Haematopoietic stem cell gene therapy for MPS IIIA

Primary outcome

To evaluate the tolerability of the IMP in MPS IIIA patients: scale
Time frame: up to 3 years
Adverse events will be recorded and graded according to an adapted Pediatric Clinical Toxicity Scale from the National Institute Allergy and Infectious Diseases (NIAID), Autoimmuno-deficiency Syndrome (AIDS) Division
To evaluate the biological efficacy of IMP post-treatment: expression of SGSH in total leukocytes
Time frame: 12 months post gene therapy
Measured by the expression of SGSH in total leukocytes within or above normal range at 12 months post-IMP treatment
To assess the safety of the IMP in MPS IIIA patients
Time frame: up to 3 years
Presence of replication competent virus and integration events in the leukocytes

7 secondary outcomes

To evaluate overall survival
Time frame: up to 3 years
To evaluate peripheral engraftment of the IMP
Time frame: within 42 days of treatments
Change in adaptive behaviour
Time frame: up to 3 years (multiple visits)
Change in cognitive function
Time frame: up to 3 years (multiple visits)
Change in patient behaviour
Time frame: up to 3 years
Change in patient quality of life
Time frame: Up to 3 years
Change in patient's daily living
Time frame: Up to 3 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
Background: PubMed 31044143Ellison SM, Liao A, Wood S, Taylor J, Youshani AS, Rowlston S, Parker H, Armant M, Biffi A, Chan L, Farzaneh F, Wynn R, Jones SA, Heal P, Gaspar HB, Bigger BW. Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex Vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA. Mol Ther Methods Clin Dev. 2019 Apr 6;13:399-413. doi: 10.1016/j.omtm.2019.04.001. eCollection 2019 Jun 14.
Background: PubMed 30136572Holley RJ, Wood SR, Bigger BW. Delivering Hematopoietic Stem Cell Gene Therapy Treatments for Neurological Lysosomal Diseases. ACS Chem Neurosci. 2019 Jan 16;10(1):18-20. doi: 10.1021/acschemneuro.8b00408. Epub 2018 Aug 23.
Background: PubMed 28651568Ghosh A, Shapiro E, Rust S, Delaney K, Parker S, Shaywitz AJ, Morte A, Bubb G, Cleary M, Bo T, Lavery C, Bigger BW, Jones SA. Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III. Orphanet J Rare Dis. 2017 Jun 26;12(1):117. doi: 10.1186/s13023-017-0675-4.
Background: PubMed 23748415Sergijenko A, Langford-Smith A, Liao AY, Pickford CE, McDermott J, Nowinski G, Langford-Smith KJ, Merry CL, Jones SA, Wraith JE, Wynn RF, Wilkinson FL, Bigger BW. Myeloid/Microglial driven autologous hematopoietic stem cell gene therapy corrects a neuronopathic lysosomal disease. Mol Ther. 2013 Oct;21(10):1938-49. doi: 10.1038/mt.2013.141. Epub 2013 Jun 7.
Background: PubMed 22547151Langford-Smith A, Wilkinson FL, Langford-Smith KJ, Holley RJ, Sergijenko A, Howe SJ, Bennett WR, Jones SA, Wraith J, Merry CL, Wynn RF, Bigger BW. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol Ther. 2012 Aug;20(8):1610-21. doi: 10.1038/mt.2012.82. Epub 2012 May 1.
Individual participant dataSharing planned: No. No, there is not a plan to make IPD available.

Related trials for Mucopolysaccharidosis Type IIIA

RecruitingPhase 1/2
Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
Mucopolysaccharidosis Type IIIA
Not yet recruitingObservational study
MPS IIIA Disease Monitoring Program
MPS IIIA, Sanfilippo Syndrome
RecruitingPhase 2/3
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
MPS IIIA, Sanfilippo Syndrome
Not yet recruitingPhase 1/2
Single Injection of rAAV9-CMV-hNAGLUop Gene for Patients With Mucopolysaccharidosis (MPS) IIIB
Sanfilippo Syndrome (MPS III)
Active, not recruitingPhase 1
Phase 1 Study of GC1130A in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo Syndrome Type A

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.

Brian Bigger principal investigator

The University of Manchester

Robert Wynn principal investigator

MFT

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 6 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 30 Mar 2025. 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 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 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?

This study is still under way. Results are not available in the source record yet.

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?

To evaluate the tolerability of the IMP in MPS IIIA patients: scale (time frame: up to 3 years). The study lists 3 primary outcomes in all. 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 NCT04201405, which also lists 5 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 30 Mar 2025.