MPS I
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.
- 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 ClinicalTrials.gov website, (www.clinicaltrials.gov); 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 | Tel: (310) 781-1399 | |
| Fax: (310) 782-2999 | Fax: (310) 782-2999 | |
| Email: ahchen@ucla.edu | Email: pdickson@ucla.edu |
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 orcha001@umn.edu. Alternatively, Teresa Kivisto is the nurse coordinator involved with this study, and she can be reached at 612-273-2924, or by email at TKIVIST1@Fairview.org.
MPSII
MPS II Intrathecal Enzyme Replacement Clinical Trial
Shire Human Genetic Therapies is sponsoring a clinical trial at the University of North Carolina at Chapel Hill to learn if direct administration of recombinant enzyme into the fluid around the brain and spinal cord is safe and a possible treatment for children with MPS II with developmental delays. The principal investigator for the clinical trial “A phase I/II safety and ascending dose ranging study of idursulfase administration via an intrathecal drug delivery device in pediatric patients with MPS II who demonstrate evidence of central nervous system involvement and who are receiving treatment with Elaprase” is Joseph Muenzer, MD, PhD.
Currently there is no approved therapy for treating the brain and spinal cord in patients with the severe form of MPS II. The goal of this study is to give a new preparation of iduronate-2-sulfatase (idursulfase-IT) directly into the fluid surrounding the brain and spinal cord (intrathecal administration). The new form of iduronate-2-sulfatase has not been used before in patients with MPS II and is considered investigational. It has not been approved by the FDA or any other regulatory agency.
This Phase I/II clinical trial is planning to enroll 16 patients with MPS II between the ages of 3 to 8 years with evidence of early neurocognitive decline using an open-label, three-dose trial design. This clinical trial will initially have both a treatment group (12 study patients) and a control group (4 study patients) with the control group eligible to receive intrathecal enzyme after a six month observational period. The monthly intrathecal administration of idursulfase-IT will be given using a Port-A-Cath® II Low Profile™ intrathecal implantable access system manufactured by Smiths Medical MD, Inc. (St. Paul, MN) that requires surgical implantation.
To be eligible for the investigational intrathecal enzyme replacement clinical trial, study patients needs to have some developmental delay, but can not be severely impaired, have received and tolerated a minimum of 6 months of weekly intravenous Elapraise and have adequate hearing (with or without hearing aids) to complete developmental assessments. Patients with MPS II are not eligible if they have a shunt for the treatment of hydrocephalus, have had a cord blood or bone marrow transplant or have other medical conditions that may place the individual at an increased risk during the investigational clinical trial.
If you are interested in obtaining more information about the clinical trial, please contact Dr. Joseph Muenzer (919.966.1447) or the study coordinator, Heather Preiss, RN (919.843.5731) at the University of North Carolina at Chapel Hill, NC.
MPS III
A Phase I/II Safety, Tolerability, Ascending Dose and Dose Frequency Study of Recombinant Human Heparan N-Sulfatase (rhHNS) Intrathecal Administration Via an Intrathecal Drug Delivery Device in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
Shire Human Genetic Therapies (Shire HGT) is developing a sulfamidase enzyme replacement therapy (ERT)rhHNS for patients with MPS IIIA. rhHNS is being administered into the cerebrospinal fluid (CSF) via a surgically implanted intrathecal drug delivery device (IDDD), because when administered intravenously (IV) it does not cross the blood brain barrier (BBB).
This study is a multicenter, multiple-dose, dose escalation study designed to evaluate the safety, tolerability, and clinical activity of up to 3 dose levels (2 doses [10 and 45mg] monthly and 1 dose [45mg] every other week for 6 months) of rhHNS administered via an IDDD in patients with Sanfilippo syndrome Type A ages greater than or equal to 3 years of age.
The study is ongoing but no longer recruiting patients. The estimated primary completion date is September 2012 (final data collection date for primary outcome measure.)
Patients who have completed all study requirements in this study Study HGT-will be invited to participate in an open-label extension study that will be designed to evaluate long term safety and clinical outcomes of intrathecal administration of rhHNS.
The Phase I / II clinical study is being conducted at two sites: Emma Children’s Hospital, Academic Medical Center in The Netherlands by Dr. Frits Wijberg and the St. Mary’s Hospital in Manchester, UK under the direction of Drs. Simon Jones and Ed Wraith. The letter to the Society from Shire about the study can be accessed on our website, under the Clinical Trials section.
Additional information about the clinical trial can be obtained at http://clinicaltrials.gov/ct2/show/NCT01155778?term=MPS+III+intrathecal&rank=1 or by contacting Tiffany Crump 484-595-8257, tcrump@shire.com or Daryll Heron +44 1256 894572, dheron@shire.com.
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 marc.tardieu@bct.aphp.fr.
Additional information about the study can be found at http://www.clinicaltrials.gov/ct2/show/NCT01474343?term=MPS+IIIA&rank=4.
MPS IV
BioMarin Pharmaceutical Inc. announced April 1, 2013 the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for Vimizim (BMN-110, elosulfase alfa), an enzyme replacement therapy for MPS IV. “Based on the positive results from our Phase 3 pivotal study, we believe that Vimizim offers a substantial benefit to patients with MPS IVA, a severely debilitating and progressive disease for which there is no current treatment,” said Hank Fuchs, M.D., Chief Medical Officer of BioMarin. BioMarin submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Vimizim on April 24, 2013.
BioMarin Pharmaceutical Inc. announced November 5, 2012 that the phase III study of GALNS met the primary endpoint of change in the six-minute walk distance at 24 weeks and was statistically significant in patients dosed at 2 mg/kg every week, with a mean increase of 22.5 meters over placebo, with continued improvement at weeks 36 and 48.
On the secondary endpoint of three minute stair climb, patients dosed with GALNS at 2 mg/kg every week showed a trend toward improvement at 24 weeks of 1.1 additional stairs per minute over placebo. Preliminary analysis of a subset of patients in the extension study (MOR-005) who have reached the 36 weeks and 48 week timepoints in the study also showed further improvement in three-minute stair climb performance.
In the other secondary endpoint, urinary keratin sulfate (KS) levels, patients dosed with GALNS at 2 mg/kg every week showed consistent and robust reduction in urinary KS with a mean difference from baseline as compared to placebo of 40.7%. Preliminary analysis of a subset of patients in the extension study who have reached the 36 and 48 week timepoints in the study showed this level of reduction was maintained.
Pulmonary function, as defined by maximum voluntary ventilation (MVV) showed a trend towards improvement from baseline of 10.3% over placebo at 24 weeks in patients dosed with GALNS at 2 mg/kg every week. Preliminary analysis of the subset of patients who reached the 48 week timepoint showed a reduction in the improvement, though an increase over baseline was maintained. Pulmonary function, as defined by forced vital capacity (FVC) also showed improvement from baseline of 3.3% over placebo at 24 weeks in patients dosed with GALNS at 2 mg/kg every week. Preliminary analysis of the subset of patients who reached the 48 week timepoint showed continued improvement.
GALNS was generally well-tolerated in the phase III clinical trial and adverse events were similar to those seem in clinical trials of other enzyme replacement therapies. BioMarin plan to apply for marketing authorizations starting in the first quarter of 2013.
Additional information can be found at www.bmrn.com and through clinicaltrials.gov, http://clinicaltrials.gov/ct2/show/NCT00787995?term=MPS+IV&rank=1.
MPS VII
On May 15, 2013, Ultragenyx Pharmaceutical Inc., announced that the open label Phase 1/2 clinical trial for MPS VII (Sly syndrome) is planned to start this year at a single center in the UK. The study will evaluate the safety, efficacy and dose of UX003 in approximately five MPS VII patients. The company anticipates that if the data from the phase 1/2 trial is positive, it would proceed with a pivotal trial with a novel design. Additional information is available on our website, including MPS 7 information portal, physician survey, diagnostic lab survey, and genetic counselors survey. Additional information can be found through clinical trials.gov.
On January 5, 2012 Ultragenyx Pharmaceutical Inc., a biotechnology company focused on developing treatments for rare and ultra-rare genetic disorders, announced it has in-licensed an enzyme replacement therapy program from St. Louis University to treat mucopolysaccharidosis VII (MPS VII). The in-licensed program is a treatment for an ultra-rare genetic, metabolic disorder that results from the deficiency of the beta-glucuronidase (GUS) enzyme. Also known as Sly syndrome, the disorder was first identified in 1973 by William S. Sly, MD, a world-renowned researcher in inherited diseases, who is currently Professor and Chairman Emeritus, Department of Biochemistry and Molecular Biology, at St. Louis University School of Medicine. Dr. Sly will collaborate with Ultragenyx on the MPS VII development program.
“We are pleased to have the opportunity to develop this treatment for MPS VII which has been in the research stage for a long time and has yet to be made available to patients. We look forward to working in collaboration with Dr. Sly and the MPS community on this program.” said Emil D. Kakkis, MD, PhD, Chief Executive Officer of Ultragenyx.
Dr. Sly noted, “After so many years of research by my laboratory and my research colleagues, I am pleased to finally have the chance to see if MPS VII patients can be successfully treated with enzyme replacement therapy. I have confidence in Ultragenyx’s ability to advance the MPS VII program through the development process and fulfill our shared goal of bringing this potentially life-changing therapy to patients. We look forward to working closely with the Ultragenyx team on this program.”
On February 28, 2012, Ultragenyx Pharmaceutical Inc., announced that the FDA office of Orphan Products Development granted orphan drug designation for UX003 for the treatment of MPS VII. On March 28, 2012 Ultragenyx was granted orphan drug designation for MPS VII by the European Medicines Agency (EMA.)
ML II/III
There currently are no therapy clinical trials for ML II/III.
