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Mucopolysaccharidosis Type 3 BPhase 1/2MPSIIIBNCT03315182

Gene Transfer Clinical Trial for Mucopolysaccharidosis (MPS) IIIB

A Phase 1/2 study testing rAAV9.CMV.hNAGLU in people with Mucopolysaccharidosis Type 3 B, run by Abeona Therapeutics, Inc at 4 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Open-label, dose-escalation clinical trial of rAAV9.CMV.hNAGLU injected intravenously through a peripheral limb vein Read more about this study

Who is it for?
Any age
Conditions the study is for
Mucopolysaccharidosis Type 3 B
What is being tested?
rAAV9.CMV.hNAGLU
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
4 sitesin 4 countries
Study dates
16 Oct 2017to 7 Apr 2022
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of MPSIIIB by both of the following two methods:
  • No detectable or significantly reduced NAGLU enzyme activity by plasma.
  • Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the NAGLU gene
  • Age: From Birth to 2 years or children older than 2 years with a minimum cognitive Development Quotient (DQ) of 60 or above (calculated by Bayley Scales of Infant and Toddler Development - Third Edition)

Who cannot join

  • Inability to participate in the clinical evaluation as determined by Principal Investigator
  • Identification of two nonsense or null variants on genetic testing of the NAGLU gene
  • Has evidence of an attenuated phenotype of MPS IIIB
  • Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
  • Active viral infection based on clinical observations as infections by Adenoviruses, Epstein-Barr Virus, Cytomegalovirus, Respiratory Syncytial Virus
  • Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer , or precludes the child from participating in the protocol assessments and follow up as autoimmune diseases requiring immunosuppression, such as juvenile rheumatoid arthritis or idiopathic thrombocytopenia purpura
Show all 21Show fewer
  • Subjects with total anti-AAV9 antibody titers ≥ 1:100 as determined by ELISA binding immunoassay
  • Subjects with a positive response for the ELISPOT for T-cell responses to AAV9
  • Serology consistent with exposure to HIV, or serology consistent with active hepatitis B or C infection
  • Bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of CSF) is contraindicated according to local institutional policy
  • Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing
  • Uncontrolled seizure disorder
  • Any item (braces, etc.) which would exclude the subject from being able to undergo MRI according to local institutional policy
  • Any other situation that precludes the subject from undergoing procedures required in this study
  • Subjects with cardiomyopathy or significant congenital heart abnormalities
  • The presence of significant non-MPS IlIB related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
  • Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.0 for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT
  • Female participant who is pregnant or demonstrates a positive urine or serum result at screening assessment (if applicable).
  • Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)
  • Previous treatment by Haematopoietic Stem Cell transplantation
  • Previous participation in a gene/cell therapy or ERT clinical trial

Trial locations and contacts

4 sites in 4 countries.

4 sites in 4 countries

United States1 site

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

Other trials in United States

France1 site

  • Armand-Trousseau Hospital

    Paris

Other trials in France

Germany1 site

  • University Hospital Hamburg-Eppendorf

    Hamburg

Other trials in Germany

Spain1 site

  • Hospital Clinico Universitario de Santiago

    Santiago de Compostela, 15706

Other trials in Spain

About this study

Official title: Phase I/II Gene Transfer Clinical Trial of rAAV9.CMV.hNAGLU for Mucopolysaccharidosis (MPS) IIIB

Open-label, dose-escalation clinical trial of rAAV9.CMV.hNAGLU injected intravenously through a peripheral limb vein

Read the detailed description

Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein. A tapering course of prophylactic enteral prednisone or prednisolone will be administered for a period of at least two months.

Being tested
rAAV9.CMV.hNAGLU
Keywords
MPS IIIB, Sanfilippo Syndrome B
Medical subject headings
Mucopolysaccharidosis III

What participants receive

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

  • rAAV9.CMV.hNAGLUBiological

    Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein.

Study groups in NCT03315182
Study groupRoleWhat they receive
Cohort 1 (Low Dose) rAAV9.CMV.hNAGLUExperimentalSubjects will receive a single infusion: • Cohort 1 (Low Dose): 2 X 10E13 vg/kg (n=2 participants)
Receives: Biological: rAAV9.CMV.hNAGLU
Cohort 2 (Med Dose) rAAV9.CMV.hNAGLUExperimentalSubjects will receive a single infusion: • Cohort 2 (Med Dose): 5 X 10E13 vg/kg (n=4-5 participants)
Receives: Biological: rAAV9.CMV.hNAGLU
Cohort 3 (High Dose) rAAV9.CMV.hNAGLUExperimentalSubjects will receive a single infusion: • Cohort 3 (High Dose): 1 X 10E14 vg/kg (n=4-8 participants)
Receives: Biological: rAAV9.CMV.hNAGLU

What is being measured

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

  1. Change from baseline in the Age Equivalent Developmental score (calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children Second Edition, based on developmental age) compared with Natural History Study data

    Measured: 24 months

  2. Product safety as defined by the incidence, type and severity of treatment-related adverse events and serious adverse events

    Measured: 24 Months

Secondary outcomes (11)

  1. Change from baseline of central spinal fluid heparan sulfate after treatment

    Measured: 24 months

  2. Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment

    Measured: 24 Months

  3. Change from baseline in CSF or plasma NAGLU enzyme activity levels after treatment

    Measured: 24 Months

  4. Change from baseline in liver and/or spleen volumes after treatment, as measured by magnetic resonance imaging

    Measured: 24 Months

  5. Change from baseline in brain volumes after treatment, as measured by magnetic resonance imaging

    Measured: 24 Months

  6. Change from baseline in the Cognitive Age Equivalent (Developmental Age) compared to Natural History Study, calculated using the Bayley Scales of Infant and Toddler Development or the Kaufman Assessment Battery for Children

    Measured: 24 Months

  7. Change from baseline in the Adaptive Age Equivalent score after treatment compared to Natural History Study data, as assessed by parent report using the Vineland Adaptive Behavior Scale II Survey form

    Measured: 24 Months

  8. Change from baseline Developmental Quotient after treatment compared to Natural History Study data assessed by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children.

    Measured: 24 Months

  9. Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Generic Core Scales total score

    Measured: 24 Months

  10. Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4) short form

    Measured: 24 Months

  11. Determination of vector shedding analysis in plasma, saliva, urine and feces will provide preliminary data for the Environmental Risk Assessment

    Measured: 24 Months

Timeline

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

  1. First posted20 Oct 2017
  2. Study start16 Oct 2017
  3. Primary completion7 Apr 2022
  4. Study completion7 Apr 2022

Why it stopped: Abeona has decided to discontinue development activities for Product ABO-101 due to a lack of drug supply and for business reasons unrelated to the product safety profile and/or signs of efficacy

Resources

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
Non-randomised
Intervention model
Single group
Model description
This is a dose escalation trial that will begin with the minimal efficacious dose as determined by preclinical studies and approved by the FDA. During the course of the trial, if safety is shown the dose will be escalated according to the clinical protocol.
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03315182
Sponsor's protocol ID
ABT-002
Acronym
MPSIIIB
Status last verified
Apr 2022
First submitted
10 Oct 2017
Last updated
5 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: There is no plan to share data

Publications

  • Fu H, Dirosario J, Killedar S, Zaraspe K, McCarty DM. Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-blood-brain barrier gene delivery. Mol Ther. 2011 Jun;19(6):1025-33. doi: 10.1038/mt.2011.34. Epub 2011 Mar 8.

    PubMed 21386820

  • Truxal KV, Fu H, McCarty DM, McNally KA, Kunkler KL, Zumberge NA, Martin L, Aylward SC, Alfano LN, Berry KM, Lowes LP, Corridore M, McKee C, McBride KL, Flanigan KM. A prospective one-year natural history study of mucopolysaccharidosis types IIIA and IIIB: Implications for clinical trial design. Mol Genet Metab. 2016 Nov;119(3):239-248. doi: 10.1016/j.ymgme.2016.08.002. Epub 2016 Aug 18.

    PubMed 27590925

  • Neufeld EF, Cantz MJ. Corrective factors for inborn errors of mucopolysaccharide metabolism. Ann N Y Acad Sci. 1971 Jul 6;179:580-7. doi: 10.1111/j.1749-6632.1971.tb46934.x. No abstract available.

    PubMed 4255108

  • Weber B, Guo XH, Kleijer WJ, van de Kamp JJ, Poorthuis BJ, Hopwood JJ. Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes. Eur J Hum Genet. 1999 Jan;7(1):34-44. doi: 10.1038/sj.ejhg.5200242.

    PubMed 10094189

  • Wijburg FA, Wegrzyn G, Burton BK, Tylki-Szymanska A. Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatr. 2013 May;102(5):462-70. doi: 10.1111/apa.12169. Epub 2013 Feb 6.

    PubMed 23336697

  • de Ruijter J, Valstar MJ, Wijburg FA. Mucopolysaccharidosis type III (Sanfilippo Syndrome): emerging treatment strategies. Curr Pharm Biotechnol. 2011 Jun;12(6):923-30. doi: 10.2174/138920111795542651.

    PubMed 21235449

  • Murrey DA, Naughton BJ, Duncan FJ, Meadows AS, Ware TA, Campbell KJ, Bremer WG, Walker CM, Goodchild L, Bolon B, La Perle K, Flanigan KM, McBride KL, McCarty DM, Fu H. Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates. Hum Gene Ther Clin Dev. 2014 Jun;25(2):72-84. doi: 10.1089/humc.2013.208. Epub 2014 Apr 10.

    PubMed 24720466

  • Ribera A, Haurigot V, Garcia M, Marco S, Motas S, Villacampa P, Maggioni L, Leon X, Molas M, Sanchez V, Munoz S, Leborgne C, Moll X, Pumarola M, Mingozzi F, Ruberte J, Anor S, Bosch F. Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy. Hum Mol Genet. 2015 Apr 1;24(7):2078-95. doi: 10.1093/hmg/ddu727. Epub 2014 Dec 18.

    PubMed 25524704

  • Hamano K, Hayashi M, Shioda K, Fukatsu R, Mizutani S. Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of human brain tissue. Acta Neuropathol. 2008 May;115(5):547-59. doi: 10.1007/s00401-007-0325-3. Epub 2007 Dec 4.

    PubMed 18060551

  • Tamagawa K, Morimatsu Y, Fujisawa K, Hara A, Taketomi T. Neuropathological study and chemico-pathological correlation in sibling cases of Sanfilippo syndrome type B. Brain Dev. 1985;7(6):599-609. doi: 10.1016/s0387-7604(85)80008-5.

    PubMed 3938624

  • Mingozzi F, High KA. Immune responses to AAV in clinical trials. Curr Gene Ther. 2011 Aug;11(4):321-30. doi: 10.2174/156652311796150354.

    PubMed 21557723

  • Saeki I, Tokunaga S, Matsuura T, Hayashida M, Yanagi Y, Taguchi T. A formula for determining the standard liver volume in children: a special reference for neonates and infants. Pediatr Transplant. 2012 May;16(3):244-9. doi: 10.1111/j.1399-3046.2011.01624.x. Epub 2011 Dec 12.

    PubMed 22151603

  • Schlesinger AE, Edgar KA, Boxer LA. Volume of the spleen in children as measured on CT scans: normal standards as a function of body weight. AJR Am J Roentgenol. 1993 May;160(5):1107-9. doi: 10.2214/ajr.160.5.8470587.

    PubMed 8470587

  • Malm G, Mansson JE. Mucopolysaccharidosis type III (Sanfilippo disease) in Sweden: clinical presentation of 22 children diagnosed during a 30-year period. Acta Paediatr. 2010 Aug;99(8):1253-7. doi: 10.1111/j.1651-2227.2010.01800.x. Epub 2010 Mar 14.

    PubMed 20337777

  • Dale DC, Fauci AS, Guerry D IV, Wolff SM. Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone. J Clin Invest. 1975 Oct;56(4):808-13. doi: 10.1172/JCI108159.

    PubMed 1159089

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing rAAV9.CMV.hNAGLU in people with Mucopolysaccharidosis Type 3 B, run by Abeona Therapeutics, Inc at 4 sites in 4 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 4 inclusion and 21 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: stopped early, as of the sponsor's last update on 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, France, Germany, Spain. 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 was stopped early (reason given: Abeona has decided to discontinue development activities for Product ABO-101 due to a lack of drug supply and for business reasons unrelated to the product safety profile and/or signs of efficacy). 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 the Age Equivalent Developmental score (calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children Second Edition, based on developmental age) compared with Natural History Study data (time frame: 24 months). The study lists 2 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 NCT03315182, which also lists 17 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 5 May 2022; AzTrials last refreshed its copy on 7 Nov 2026.

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