Clinical Trials

MPS I Intrathecal Enzyme Replacement Clinical Trial Information

The Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, California and the University of Minnesota are collaborating on a Study of Intrathecal Enzyme Replacement Therapy for cognitive decline in patients with Mucopolysaccharidosis Type I.


The purpose of this research study is to find out whether giving enzyme replacement therapy with Aldurazyme® as an injection directly into the cerebral spinal fluid (the fluid around the spinal cord and the brain) can stabilize (keep from getting worse) or improve cognitive decline in patients who have MPS I. The term “cognitive decline” refers to a change for the worse in our ability to think and learn. Difficulty with thinking, memory, language, concentration and decision making are some signs of cognitive decline.


To be eligible for this study, you or your child must be willing and able to comply with the study procedures and meet certain criteria:

  • 6 years of age or older
  • Diagnosed with MPS Type I
  • Show evidence of cognitive decline on a screening evaluation


Study participants will have:

  • Up to 10 treatments given 1-3 months apart over 2 years (treatment group)

or 4 treatments given 3 months apart beginning at month 12 (control group).

  • Physical Examinations (general and neurologic)
  • Neuropsychological testing for cognitive decline and MRI of the brain,
  • Reimbursement/payment of travel expenses


Additional details about this clinical trial can be found at the website, (; search under “mucopolysaccharidosis”.


If you are interested in this study or would like more information, please contact:

Dr. Agnes Chen                                 or                    Dr. Patricia Dickson

Tel: (310) 222-4160                                                    (310) 782-2999



MPS I Intrathecal ERT for Children Being Considered for Transplantation

The University of Minnesota has recently obtained FDA approval for the delivery of Laronidase into the spinal fluid of children with Hurler syndrome being considered for marrow/cord blood transplantation.  The goal of these studies is to decrease the neuropsychologic decline that has been observed in children with Hurler from the time the patients are initially evaluated to the time they are 1 year from transplantation.  The hypothesis is that there is a significant delay in achieving sufficient enzyme levels in the brain following transplantation, and that this may be overcome by giving enzyme into the spinal fluid until this occurs.  Patients with Hurler syndrome that are between 8 and 36 months of age that have not previously received enzyme therapy and are being considered for transplantation at the University of Minnesota are eligible. Patients receiving Laronidase in the spinal fluid will also be on intravenous Laronidase prior to transplant.  The study will involve 4 doses of Laronidase given during a lumbar puncture (LP, or spinal tap) approximately 3 months before transplantation, at the time of admission to the hospital for the transplant, 3 months after the transplant and 6 months after the date of the transplant.  The Principal Investigator of the study is Dr. Paul Orchard, who can be reached at 612-626-2961, or by email at  Alternatively, Teresa Kivisto is the nurse coordinator involved with this study, and she can be reached at 612-273-2924, or by email at



A Controlled, Randomized, Two-arm, Open-label, Assessor-blinded, Multicenter Study of Intrathecal Idursulfase-IT Administered in Conjunction with IV Elaprase in Pediatric Patients with Hunter Syndrome and Early Cognitive Impairment (AIM-IT)

Protocol Number : HGT-HIT-094

Phase of Development : Phase II/III

Investigational Treatment : Idursulfase-IT via Intrathecal (IT) Administration


The purpose of this study is to determine the effect of the Idursulfase-IT treatment regimen in conjunction with IV Elaprase therapy, on cognitive and adaptive behavior as measured by the DAS-II (Differential Ability Scales, Second Edition) in pediatric patients with Hunter syndrome and early cognitive impairment.

1. This study will be conducted in English and Spanish speaking countries, with the following being considered: Argentina, Australia, Canada, Colombia, Mexico, United Kingdom, United States, and Spain.

2. This is a controlled, randomized, two-arm, open-label, assessor-blinded, multicenter study to determine the effects on clinical parameters of neurodevelopmental status of monthly IT administration of Idursulfase-IT for 12 months in pediatric patients with Hunter syndrome and early cognitive impairment who have previously received and tolerated a minimum of 4 months of therapy with Elaprase.

3. A total of 42 patients will be randomized to either receive monthly IT treatment or to a no treatment control arm in a 2:1 ratio. All patients will be on standard of care IV Elaprase throughout the study.

4. The SOPH-A-PORT Mini S, Implantable Access Port will be utilized for IT administration of Idursulfase-IT. a. In the USA, a limited number of patients (9 in total) may be initially enrolled into the study. If randomized to the IT treatment arm, these patients may initially receive consecutive monthly IT doses of Idursulfase-IT by lumbar puncture. At such time that the use of the SOPH-A-PORT Mini S is authorized by the FDA, these patients and any patient enrolled thereafter who is to receive treatment, will be implanted with the device.

5.  Patients that are under the age of 3 may be eligible for inclusion into a sub-study which         does not include a no treatment arm.


Key Inclusion Criteria

• Males >3 and <18 years of age

• Documented diagnosis of MPS II o Mutation in the I2S gene leaving FMR1 and FMR2 genes intact

• Evidence of early cognitive impairment due to MPSII o GCA score >55 and <85 (General Conceptual Ability score, as measured by the DAS-II) Keyword: MPSII, Hunter syndrome


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A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration via an Intrathecal Drug Delivery Device (IDDD) in Pediatric Patients with Early Stage Mucopolysaccharidosis Type IIIA

Protocol Number : HGT-SAN-093

Phase of Development : Phase IIB

Investigational Treatment : Recombinant Human Heparan N Sulfatase (HGT-1410) via Intrathecal (IT) Administration


The purpose of this study is to assess the potential clinical efficacy of HGT-1410 administered via a surgically implanted IDDD in patients with MPS IIIA.

1. This study will be conducted globally, with the following countries being considered: Argentina, Brazil, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, and United States.

2. This is an open-label, randomized, parallel group, controlled, multicenter study designed to evaluate the efficacy and safety of HGT-1410 administered via an IDDD versus no treatment in patients at a relatively early stage of MPS IIIA disease.

3. A total of 18 patients will be randomized to one of three groups: 45 mg HGT-1410 administered IT every 2 weeks (6 patients); 45 mg of HGT-1410 administered IT every 4 weeks (6 patients); or a no treatment control arm (6 patients).

4. The SOPH-A-PORT Mini S, Implantable Access Port will be utilized for IT administration of HGT-1410.


Key Inclusion Criteria

• Age ≥12 months and ≤ 48 months

• Documented diagnosis of MPS IIIA • documented deficiency in sulfamidase enzyme activity of ≤10% of the lower limit of the normal range as measured in fibroblasts or leukocytes, and

• Documented mutations in each SGSH allele OR there must be documentation of mutations in each SGSH allele in a sibling affected by MPS IIIA

• Developmental Quotient score ≥60%, assessed by cognitive evaluation at screening assessment using the Bayley Scores of Infant Development, Version III (BSID-III) Keyword: MPSIIIA, Sanfilippo syndrome type A



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Intracerebral Gene Therapy for MPS IIIA


Lysogene announced May 13, 2013 that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to its lead gene therapy product SAF-301 for the treatment of MPS IIIA.  Lysogene’s 2014-2017 development plan, including the clinical site(s) determination for the next clinical development, is currently under preparation.


A one-year, phase I/II gene therapy clinical trial for MPS IIIA is being conducted at Hôpital Bicêtre – Assistance Publique des Hôpitaux de Paris.  This is an open-label, single arm, monocentric, phase I/II clinical study evaluating the tolerance and the safety of intracerebral administration of adeno-associated viral vector serotype 10 carrying the human SGSH and SUMF1 cDNAs for the treatment of Sanfilippo type A syndrome The treatment plan consists of a direct injection of the investigational medicinal product SAF-301 to both sides of the brain through 6 image-guided tracks, with 2 deposits per track, in a single neurosurgical session in four patients with MPS IIIA.

The primary objective is to assess the tolerance and the safety associated to the proposed treatment through a one-year follow up.

The secondary objective is to collect data to define exploratory tests that could become evaluation criteria for further clinical phase III efficacy studies.

Lysogene, the biotechnology company sponsoring the clinical trial, announced June 14, 2012 that the last planned patient had been treated.

The primary investigator is Dr. Marc Tardieu, Hôpital Bicêtre – Assistance Publique des Hôpitaux de Paris Recruiting Le Kremlin Bicêtre, France, 94275, +33 1 45 21 32 23

Additional information about the study can be found at



BioMarin announced February 14, 2014 FDA approval for Vimizim™ for the treatment of patients with MPS IVA (Morquio A syndrome.)  On February 20, 2014 BioMarin announced that that the European Commission (EC) is expected to render a final decision for VIMIZIM in the second quarter of 2014.  If approved by the EC, BioMarin would receive marketing authorization for VIMIZIM in all EU Member States.

The safety and efficacy of VIMIZIM were assessed in a 24-week, randomized, double-blind, placebo-controlled clinical trial of 176 patients with MPS IVA (MOR-004). The primary endpoint of the trial, change in six-minute walk distance at 24 weeks, was statistically significant in patients receiving weekly infusions of VIMIZIM at the dose of 2 mg/kg with a mean increase of 22.5 meters (p=0.0174) over placebo.

In patients who continued to receive VIMIZIM 2 mg/kg once per week for another 48 weeks (for a total of 72-week exposure), walking ability was sustained to a similar level that was achieved during the first 24 weeks of treatment in the placebo-controlled trial, MOR-004.

Overall, sustained improvements across multiple efficacy measurements and across multiple clinical trials provided evidence of clinical benefit to patients with MPS IVA, a chronic, progressive disease in which clinical deterioration is the expected course.

The adverse events observed in clinical trials were similar to those seen in other enzyme replacement therapies.  In the Phase 3 trial, the most common adverse reactions (≥10% and a higher incidence than placebo) that occurred were pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue.  No new types of adverse reactions were reported in the Phase 3 extension trial. The most common adverse reactions (≥10%) observed across pre-marketing clinical trials were similar in type and frequency as those observed in the placebo-controlled trial. Acute reactions requiring intervention were managed by either temporarily interrupting or discontinuing infusion, and administering additional antihistamine, antipyretics, or corticosteroids.

BioMarin will offer support to patients through its BioMarin Patient & Physician Support (BPPS) team. Through BPPS, patients receive live, personalized support by a specialized case manager who will research insurance coverage and alternative benefit options. BPPS will help patients obtain coverage and minimize out-of-pocket expenses and find alternative financial assistance for treatment. To reach a BPPS case manager, please call, toll-free, 1-866-906-6100 or e-mail For more information about VIMIZIM, please visit



Ultragenyx Pharmaceutical Inc., announced December 4, 2013 the dosing of the first patient in a Phase 1/2 study of recombinant human beta-glucuronidase (rhGUS, UX003) for MPS7, in Manchester, UK. MP7 is an ultra-rare autosomal recessive lysosomal storage disorder characterized by a deficiency of the enzyme beta-glucuronidase that results in a severe multi-system disease.


William Sly, MD, Chairman Emeritus of the Department of Biochemistry at Saint Louis University commented, “Patients, families, and researchers have been waiting many years for this advancement in the treatment of MPS7. The initiation of clinical testing of rhGUS is

the culmination of decades of work.”


The Phase 1/2 open-label clinical trial will assess the safety and efficacy of rhGUS in a 12-week primary analysis phase, followed by dose-exploration and long-term extension. Five patients between 5 and 30 years of age inclusive will be enrolled and administered rhGUS every other week via intravenous infusion. Interim data from the Phase 1/2 study is expected in 2014.


“MPS7 is a devastating condition that has been neglected by the drug development community despite 20 years of extensive nonclinical research led by Dr. Sly and his colleagues,” said Emil D. Kakkis, MD, PhD, Chief Executive Officer of Ultragenyx. “The initiation of this Phase 1/2 study is an important milestone for Ultragenyx and for patients with MPS7.


Additional information about the study can be found at:



There currently are no therapy clinical trials for ML II/III.