Treatment Clinical Trials

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 5220246 Hamburg
Principal Investigator: Dr. Nicole Maria Muschol

Tel: +49-40-7410-53710    fax: +49-40-7410-56527

MPS II

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)

www.shiretrials.com
www.clinicaltrials.gov Keyword: MPSII, Hunter syndrome

Medical Information North America
US_ShireHGT_MedicalInformation@shire.com
866-888-0660 option 2

 

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

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)

www.shiretrials.com
www.clinicaltrials.gov Keyword: MPSIIIA, Sanfilippo syndrome type A

Contact
Medical Information North America
US_ShireHGT_MedicalInformation@shire.com
+1-866-888-0660 option 2

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.

 

Intracerebral Gene Therapy for MPS IIIA

In July 2015 Alcyone Lifesciences, Inc., a leader in neural intervention systems for neurological conditions and targeted drug delivery, and Lysogene, a privately held biotechnology company and leader in recombinant adeno-associated virus (rAAV) based gene therapy for the CNS, announced they have entered into a collaboration. Lysogene and Alcyone Lifesciences will join forces to evaluate the intraparenchymal delivery of Lysogene’s proprietary rAAV to treat patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo A, utilizing the Alcyone MEMS Cannula (AMC) targeted delivery platform.

 

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 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 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 completed Phase I/II study in four MPS IIIA children demonstrated that the gene therapy and neurosurgical procedure is safe, well tolerated and exploratory efficacy profiles are encouraging

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.

 

Enzyme Replacement Therapy for MPS IIIB – Alexion Pharmaceuticals

Alexion Pharmaceuticals (formerly Synageva BioPharma Corp.) announced January 26, 2015 dosing with SBC-103 in patients with mucopolysaccharidosis IIIB (MPS IIIB, Sanfilippo B syndrome) has begun as part of a Phase 1/2 study.  In addition, the U.S. Food and Drug Administration (FDA) recently granted SBC-103 Fast Track designation.  Fast Track is a process designed to facilitate development and expedite review of drugs to treat serious and life-threatening conditions and fill an unmet medical need to get important new drugs to patients expeditiously. Synageva BioPharma Corp. announced June 8, 2015 the completion of enrollment in a phase 1/2 trial with SBC-103.

The trial reached its targeted enrollment of nine patients, who are two years of age or greater but less than 12 years of age, with a definitive diagnosis of MPS IIIB and developmental delay.  Patients are being treated in one of three different dosing cohorts (0.3 mg/kg, 1.0 mg/kg or 3.0 mg/kg) with every other week intravenous administrations of SBC-103 for 24 weeks.  Patients who meet qualifying criteria may continue dosing with SBC-103 for an extended period.

The primary endpoint of the trial is safety and tolerability of intravenous administration of SBC-103 in patients with MPS IIIB.  The study will also evaluate the effects of dosing with SBC-103 on the change from baseline levels of total heparan sulfate (HS) in urine, serum, and cerebral spinal fluid (CSF), as well as measure the effects on neurocognitive and developmental function and change in brain structures as assessed by magnetic resonance imaging.

The advancement of SBC-103 towards the clinic was supported by preclinical studies demonstrating that intravenously administered SBC-103 was able to cross the blood-brain barrier and reduce HS storage in the brain in an MPS IIIB animal model.  In addition, SBC-103 demonstrated transport across an in vitro model of the blood-brain barrier and distributed into the CSF in non-human primate studies.

Additional information about the study can be found at:

https://clinicaltrials.gov/ct2/show/NCT02324049?term=MPS+IIIB&rank=5

 

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 33 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, as well as assessments of behavior, sleep and quality-of-life.  This study is anticipated to last 48 weeks and will involve visits every 12 weeks to the study center. This study is intended to provide baseline information to help in determining whether these children subsequently benefit from treatment in the next phase of the program. This observational study is now open.

In the near future, BioMarin plans to start the second study. The second study will be a treatment study in which children will receive an investigational enzyme replacement therapy. This will be provided as an infusion via a port which delivers the enzyme into the brain. This study will be run at the same centers as the observational study. The first phase of this study will enroll a small number of patients in early 2016 to assess safety at several doses. The second phase of this study is targeted to start in mid-2016 and will last for 48 weeks.  In order to enroll in the second phase of the treatment study the child must have completed the observational study or the first part of the treatment study.  The intention is to provide treatment to all of the children who have entered into the observational study.

Enrollment in this program will be limited to children from countries in which there is a study site. Please visit www.clinicaltrials.gov for more details about the observational study as well as for a list of enrolling study sites.

For more information visit: http://www.bmrn.com/

 

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.

 

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

www.clinicaltrials.gov/ct2/show/NCT01856218

 

ML II/III

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