MPS I
Sangamo Therapeutics recently announced that Phase 1/2 clinical trials are open and enrolling adult subjects, 18 years of age and older, to begin testing the potential benefits of the company’s new gene therapies in MPS I and MPS II patients. Sangamo’s gene therapies for MPS I and II are based on the company’s in vivo genome editing approach, which is designed as a single treatment to provide life-long production of corrective IDUA (MPS I) and IDS (MPS II) enzymes from the patient’s own liver and potentially eliminate the need for chronic enzyme replacement therapy (ERT). The U.S. FDA has already reviewed and cleared Sangamo’s Investigational New Drug, or IND, applications to begin clinical trials and Sangamo is now enrolling subjects.
Once these clinical trials have shown that Sangamo’s MPS I and MPS II gene therapies are safe and effective in adults, the company plans to initiate clinical trials for pediatric MPS I and MPS II patients who make up a large portion of the MPS community and would benefit most from a one-time, permanent treatment early on in life.
For more details about Sangamo’s Phase 1/2 clinical trials for MPS I and MPS II, you can visit the study websites at www.empowersmpstrial.com (for MPS I) and www.mps2study.com (for MPS II). You can also learn more about Sangamo’s clinical trials at www.clinicaltrials.gov (Keyword: Sangamo) or contact Sangamo Therapeutics at clinicaltrials@sangamo.com.
EMPOWERS (SB-318-1502) MPS I Gene Therapy Clinical Trial
The EMPOWERS clinical research study is looking for adults with MPS I to test SB-318, an investigational type of gene therapy called genome editing, as a potentially lasting treatment. Sangamo Biosciences, Inc. is studying SB-318 to see if it’s safe and tolerable, and learn more about its effectiveness at enabling your body to permanently produce the IDUA enzyme needed to reduce MPS I symptoms.
SB-318 is a single infusion into a vein. Afterward, your health will be followed for about 3 years to see how you’re responding to the therapy. Patients who are receiving enzyme replacement therapy (ERT) can continue receiving treatment while on study. Patients may also have received hematopoietic stem cell transplant (HSCT) in the past.
Qualification criteria for this clinical research study include:
- At least 18 years old
- Diagnosed with MPS I
- Able to use corticosteroids
Qualified participants will receive:
- Single transfusion of investigational gene therapy (SB-318) for MPS I
- Study-related medical care
- Reimbursement for travel (Transportation assistance may be available)
For additional information regarding the study and study sites, please go to www.clinicaltrials.gov and search for identifier number NCT02702115.
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 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 (310) 781-1399
Fax: (310) 782-2999 (310) 782-2999
Email: ahchen@ucla.edu pdickson@ucla.edu
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 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.
AGT-181 Phase I Enzyme Replacement Clinical Trial
ArmaGen, Inc., a privately held biotechnology company focused on developing novel therapies to treat severe neurological disorders. The purpose of the trial is to test the safety and determine a well-tolerated dose of an investigational treatment AGT-181 in people with attenuated MPS I (Scheie and Hurler-Scheie syndromes).
AGT-181 is an investigational enzyme replacement therapy designed to treat both the body-related and central nervous system-related symptoms and complications of MPS I.
Currently approved treatments for MPS I are unable to penetrate the blood-brain barrier, a filter that protects the brain from harmful substances like toxins and bacteria but allows vital substances like insulin to cross from the blood into the brain. AGT-181 is designed to cross the blood-brain barrier in the same way insulin does.
The study is a Phase 1 trial in adults with attenuated MPS I (Hurler-Scheie and Scheie syndromes). A Phase 1 trial tests a new drug in a small group of patients to evaluate the drug’s safety, identify potential side effects, and determine a dose of the medication for further testing.
Patients in the trial will receive weekly infusions of AGT-181 at assigned doses that range from 1 mg/kg for the first dose group of patients enrolled and increase to 3.0 mg/kg. Additional higher dose levels may be added. AGT-181 will be administered intravenously over a 3-4 hour period for eight weeks.
Following treatment, investigators will collect a sample of cerebrospinal fluid, which surrounds and protects the brain and spinal cord, through a minimally-invasive diagnostic test. This fluid will be tested to confirm whether there is a reduction in levels of complex sugars that build up in the bodies of people living with MPS I.
Key criteria for participation are:
– Patients age 18 years or older diagnosed with attenuated MPS I (Hurler-Scheie or Scheie syndromes)
– Must provide voluntary written consent.
– Patients on current enzyme replacement therapy (ERT) must discontinue ERT for at least 6-weeks before and during the duration of the trial.
Examples of factors that make patients not eligible for the trial include if the patient has:
– Received an investigational drug within the past 90 days.
– A medical condition or serious illness that, in the opinion of the investigator, may significantly interfere with study compliance.
– Clinically significant spinal cord compression or evidence of cervical instability.
ArmaGen is committed to helping families manage the logistics and expenses of participating in the trial. Our reimbursement plan addresses travel, subsistence (meals and lodging) and stipend (given by study site institution directly to participant) based on specific guidelines and requirements, and taking into account the financial and/or medical needs of individual participants.
For more information about the study and study centers, please see www.clinicaltrials.gov, using the identifier number NCT02371226.
PTC Therapeutics, Inc
We are pleased to announce a clinical trial of ataluren in patients with mucopolysaccharidosis type I (MPS I) caused by a specific type of genetic mutation called a “nonsense mutation”. This study will be conducted in the UK and Germany. Patients from other countries may travel to study sites in Germany to participate in the study.
Approximately 60 to 80% of patients with MPS I have the disease due to a nonsense mutation. In these patients, ataluren has the potential to restore the missing enzyme, α-L-iduronidase. Ataluren is an investigational drug, taken orally, that has been studied in over 750 people, including healthy volunteers and patients with other genetic disorders, and recently was approved in Europe for the treatment of nonsense mutation Duchenne muscular dystrophy. Results of nonclinical studies (ie, laboratory and animal studies) suggest that ataluren also may benefit patients with nonsense mutation MPS I.
The study is a Phase 2, open-label study to evaluate the safety, pharmacokinetics (or how the body affects the drug), and effectiveness of ataluren in at least 15 patients with nonsense mutation MPS I.
Suitable study candidates must meet the following criteria:
– Age >2 years
– Clinical diagnosis of MPS I
– A nonsense mutation in at least 1 allele of the α-L-iduronidase (IDUA) gene
– Either not on enzyme replacement therapy OR on a stable dose of enzyme replacement therapy for at least 6 months
Subjects may or may not have received a hematopoietic stem cell transplant in the past.
If a candidate’s genetic mutation is unknown, assistance with genetic testing may be available.
Patients not on enzyme replacement therapy will receive ataluren for 12 weeks.
Patients on enzyme replacement therapy will receive ataluren in combination with enzyme replacement therapy for 12 weeks followed by ataluren alone for an additional 4 weeks (total of 16 weeks).
Patients will visit the clinic once every 4-6 weeks, or certain visits may be performed at a local laboratory or by a visiting nurse if it is more convenient. Study assessments will include 2 spinal taps and regular vital sign measurements, physical examinations, electrocardiograms, and blood and urine measurements.
Travel and lodging expenses associated with all on-site visits will be funded by the sponsor, PTC Therapeutics, Inc. Additionally, the MPS Society will coordinate all travel and lodging arrangements for such visits in order to reduce burden on the patient.
Information can be accessed via the EMA Clinical trial listing
For more information, please contact the study sites directly:
**For UK residents only**
Royal Manchester Children’s Hospital NHS Foundation Trust
Manchester, United Kingdom
PI: Jones, Simon
Ph: +44 (0) 161 701 2137
Email: simon.jones@cmft.nhs.uk
**For all other countries**
Centre for Rare Diseases
Horst Schmidt Klinik
Wiesbaden, Germany
Principal Investigator: Christina Lampe, MD
Contacts:
Maurizio Scarpa, MD Christina Lampe, MD
Phone: +49 151 14224959 Phone: +49 (0) 611 432314
Email: Maurizio.Scarpa@helios-kliniken.de Email: Christina.Lampe@helios-kliniken.de
International Center for Lysosomal Disorders – University Medical Center Hamburg-Eppendorf
Dept. of Pediatrics, Bldg N23
Martinistra ße 52
20246 Hamburg
Principal Investigator: Dr. Nicole Maria Muschol
Tel: +49-40-7410-53710 fax: +49-40-7410-56527
MPS II
Sangamo Therapeutics recently announced that Phase 1/2 clinical trials are open and enrolling adult subjects, 18 years of age and older, to begin testing the potential benefits of the company’s new gene therapies in MPS I and MPS II patients. Sangamo’s gene therapies for MPS I and II are based on the company’s in vivo genome editing approach, which is designed as a single treatment to provide life-long production of corrective IDUA (MPS I) and IDS (MPS II) enzymes from the patient’s own liver and potentially eliminate the need for chronic enzyme replacement therapy (ERT). The U.S. FDA has already reviewed and cleared Sangamo’s Investigational New Drug, or IND, applications to begin clinical trials and Sangamo is now enrolling subjects.
Once these clinical trials have shown that Sangamo’s MPS I and MPS II gene therapies are safe and effective in adults, the company plans to initiate clinical trials for pediatric MPS I and MPS II patients who make up a large portion of the MPS community and would benefit most from a one-time, permanent treatment early on in life.
For more details about Sangamo’s Phase 1/2 clinical trials for MPS I and MPS II, you can visit the study websites at www.empowersmpstrial.com (for MPS I) and www.mps2study.com (for MPS II). You can also learn more about Sangamo’s clinical trials at www.clinicaltrials.gov (Keyword: Sangamo) or contact Sangamo Therapeutics at clinicaltrials@sangamo.com.
AGT-182 Phase I Clinical Trial in patients with MPS II, Hunter syndrome
This trial, sponsored by ArmaGen, is to test the safety and determine a well-tolerated dose of an investigational treatment AGT-182 in adults with MPS II. AGT-182 is an investigational enzyme replacement therapy designed to treat both the body-related and central nervous system-related symptoms and complications of MPS II.
Currently approved treatments for MPS II are unable to penetrate the blood-brain barrier (BBB), a filter that protects the brain from harmful substances like toxins and bacteria but allows vital substances like insulin to cross form the blood to the brain. AGT-182 is designed to cross the BBB in the same way insulin does.
Patients will receive weekly infusions of AGT-182 at assigned doses that range from 1mg/kg for the first dose of patients enrolled and increase to 3.0 mg/kg. Additional higher dose levels may be added. AGT-182 will be administered intravenously over a three hour period for eight weeks. Study investigators will collect a sample of cerebrospinal fluid, which surrounds and protects the brain and spinal cord. This fluid will be tested to help confirm that AGT-182 is crossing the BBB.
Key criteria for participation are:
– Male patients age 18 years or older diagnosed with Hunter syndrome.
– Must provide voluntary written consent.
– Patients on current enzyme replacement therapy (ERT) must discontinue ERT for at least 6-weeks before and during the duration of the trial.
There are a few factors that make patients not eligible for the trial. Examples include if the patient has:
-Received an investigational drug within the past 90 days.
– A medical condition or serious illness that, in the opinion of the investigator, may significantly interfere with study compliance.
– Clinically significant spinal cord compression or evidence of cervical instability
For more information about the study and study centers, please see www.clinicaltrials.gov using the identifier number NCT02262338.
MPS III
Lysogene has completed a phase I/II gene therapy trial in patients with MPS IIIA
A phase I/II gene therapy clinical trial for MPS IIIA was conducted at Hôpital Bicêtre – Assistance Publique des Hôpitaux de Paris. This was 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 consisted of a direct injection of the investigational medicinal product LYS-SAF301 in a single neurosurgical session in four patients with MPS IIIA. The study demonstrated that the gene therapy and neurosurgical procedure is safe, well tolerated and exploratory efficacy profiles are encouraging. [http://online.liebertpub.com/doi/abs/10.1089/hum.2013.238?journalCode=hum]. It is now five years since the first patient was dosed. A second generation improved gene therapy product LYS-SAF302 has been developed with the aim of moving into a phase II/III pivotal trial.
For more information, contact Lysogene at contact@lysogene.com
Lysogene has initiated a global observational study of patients with MPS IIIA in preparation for its gene therapy trial.
Lysogene has launched a prospective, observational study of patients, who are aged nine years old or younger, with mucopolysaccharidosis IIIA (MPS IIIA) to better understand their health problems and how to measure these problems over time. This is an observational study, so no experimental drug will be given. The study is planned before the start of Lysogene’s gene therapy trial. Patients will receive study related care. The information to be learned will help lead to faster, better trial design and understanding future therapeutic effects. For more information, visit Lysogene‘s website.
Lysogene plans its phase II/III trial of gene therapy in MPS IIIA. The aim of this study is to determine that the second generation improved gene therapy product LYS-SAF302 is effective and safe.
Inclusion and exclusion criteria are being defined for participation in the phase II/III study. Clinical trial sites will be selected globally. We currently envisage that patients recruited to the trial will need to relocate to one of the clinical trial sites for an initial period of a few weeks. Additional visits to the clinical site, for a day or two, will be planned every 6 months. For more information, visit Lysogene‘s website.
Enzyme Replacement Therapy for MPS IIIB – BioMarin Pharmaceutical Inc.
BioMarin Pharmaceutical Inc. has recently started a program for children with MPS IIIB (Sanfilippo B syndrome). This will involve multiple centers around the world. The program will enroll up to 30 children between the age of 1 and 10 years, although the majority of children will be under 6 years old. The program consists of two studies.
The first study is an observational study of children with MPS IIIB and includes testing of cognitive and adaptive function. The observational study lasts for 48 weeks. These tests explore how the child thinks and acquires new information as well as how the child deals with daily living. There are also assessments of behavior and quality of life. This study is intended to provide baseline information about how MPS IIIB progresses in the absence of treatment. This baseline information can then be compared to disease progression information from BioMarin’s subsequent treatment study (both for individual children and in aggregate).
The observational study is already opened at sites in Australia, Colombia, Germany, Spain, Taiwan, Turkey and the United Kingdom. We have just recently opened a new site in Oakland, CA in the United States. Several children have already enrolled in the observational study.
The second study is a treatment study in which children will receive an investigational enzyme replacement therapy, known as BMN 250. The enzyme is administered directly to the brain as an infusion via a surgically implanted port. This study will be run at selected centers which are also part of the observational study. The first phase of this study, which is designed to assess safety at several doses in a small number of patients, is ongoing. To enroll in the second phase of the treatment study, a child must have completed the observational study as outlined above, or have completed the first part of the treatment study.
Your child’s doctor is the best source of information about the care of your child.
For more information about active clinical studies, including Sanfilippo B, please visit www.clinicaltrials.gov
MPS IIIA/B
Abeona is developing next generation adeno-associated viral (AAV)-based gene therapies for MPS III (Sanfilippo syndrome), which involves a one-time delivery of a normal copy of the defective gene to cells of the central nervous system with the aim of reversing the effects of the genetic errors that cause the disease.
After a single dose in Sanfilippo preclinical models, ABO-101 and ABO-102 induced cells in the CNS and peripheral organs to produce the missing enzymes and help repair damage caused to the cells. Preclinical in vivo efficacy studies in Sanfilippo syndrome have demonstrated functional benefits that remain for months after treatment. A single dose of AB0-101 or AB0-102 significantly restored normal cell and organ function, corrected cognitive defects that remained months after drug administration, increased neuromuscular control and increased the lifespan of animals with MPS III over 100% one year after treatment compared to untreated control animals. These results are consistent with studies from several laboratories suggesting AAV treatment could potentially benefit patients with for Sanfilippo Syndrome Type A and B, respectively. In addition, safety studies conducted in animal models of Sanfilippo syndromes have demonstrated that delivery of AB0-101 or AB0-102 are well tolerated with minimal side effects.
For more information, please contact Abeona or visit clinicaltrials.gov.
MPS IVA
There currently are no treatment clinical trials for MPS IVA.
MPS VII
Ultragenyx Pharmaceutical Inc. is a biopharmaceutical company founded by Emil Kakkis, M.D., Ph.D., working to develop novel products for the treatment of rare and ultra-rare diseases.
Ultragenyx has three ongoing clinical trials studying an investigational enzyme replacement therapy (rhGUS; UX003) in patients with MPS VII:
– Phase 2 in patients under 5 years of age; this clinical trial is active and currently enrolling patients.
– Phase 1/2 in patients 5-30 years of age; enrollment is complete.
– Phase 3 in patients 5-35 years of age; enrollment is complete.
Recent results from the ongoing Phase 1/2 study determined the optimal dose of rhGUS along with providing other supportive data. These data showed that among the three dose levels tested, the 4 mg/kg dose of rhGUS led to the greatest reduction of glycosaminoglycans (GAGs) in the urine, with an average reduction of GAGs in the urine of approximately 60%. In two patients who had enlarged livers at the start of the study, there was a decrease in liver size. There was an improvement in pulmonary (lung) function observed in the one patient who was able to perform the evaluations, and improvement in fatigue in the 3 patients enrolled. No serious adverse events or treatment-related infusion-associated reactions related to the investigational enzyme replacement therapy were reported in the study after 36 weeks of treatment. The most common adverse events were respiratory disorders, infections, joint pain, and leakage of infusion drug out of the vein into the surrounding tissues.
Three infants and one adolescent patient with MPS VII are currently being treated with UX003 under expanded access. Two of the four patients had a history of hydrops fetalis.
For more information, please visit www.ultragenyx.com or email questions to patientadvocacy@ultragenyx.com.
www.clinicaltrials.gov/ct2/show/NCT01856218
ML II/III
There currently are no therapy clinical trials for ML II/III.