What if I have a question?
What is a clinical trial?
A clinical trial is a research study that explores the safety and/or effectiveness of a potential new treatment in humans.
What is a Phase 1 clinical trial?
A Phase 1 clinical 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.
What is MPS I?
Mucopolysaccharidosis type I, or MPS I, is a rare, hereditary metabolic disorder. In people with MPS I, an enzyme called iduronidase (IDUA) is missing or does not work properly. This leads to an abnormal buildup of complex sugars in tissues throughout the body, including the skeleton, joints, brain, spinal cord, heart, spleen and liver.
MPS I affects the brain in children, resulting in debilitating signs and symptoms that include developmental delay and progressive mental decline. Hurler syndrome also affects the spinal cord in children, resulting in loss of physical function, impaired language development (due to hearing loss and an enlarged tongue), corneal and retinal damage, carpal tunnel syndrome and restricted joint movement.
There are three main types of MPS I based on severity. The attenuated (less severe) types are Scheie (the mildest) and Hurler-Scheie (the intermediate form of the disease). The severe type is Hurler (the most severe).
What is the difference among Hurler, Hurler-Scheie, and Scheie syndromes?
MPS I is broken down into three subtypes: Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome. Hurler syndrome is generally considered the most severe and Scheie syndrome the least severe. Hurler-Scheie syndrome encompasses patients that fall in between these two extremes.
Although less severe than Hurler syndrome, patients with Hurler-Scheie patients may suffer from mild cognitive impairment or problems with attention. Scheie patients generally have a later onset and milder symptoms with a slower disease progression, although they can develop significant systemic morbidity.
AGT-181 AND THE AGT-181-101 CLINICAL TRIAL
What is AGT-181?
AGT‑181 is an investigational enzyme replacement therapy (ERT) designed to treat symptoms and complications of MPS I both in the body (somatic) and the central nervous system (CNS), consisting of the brain and spinal cord.
AGT-181 is designed to cross the blood-brain barrier (BBB) in the same way insulin does. AGT-181 is not approved by the U.S. Food and Drug Administration.
What is the blood-brain barrier (BBB)?
The BBB is a barrier that filters substances crossing from the blood into the brain. It protects the brain from bacteria and other foreign substances, but allows the passage of vital nutrients that are required for the proper health and function of the brain. Insulin is one example of such a substance that can get into the brain through the BBB.
How is AGT-181 different from Aldurazyme®?
AGT-181 is designed to cross the BBB and may treat many of the severe and progressive neurological complications of the disease. Aldurazyme® is unable to cross the BBB, and therefore does not treat the brain.
How is AGT-181 similar to Aldurazyme?
AGT-181 and Aldurazyme both contain a replacement iduronidase (IDUA) enzyme.
AGT-181 carries the IDUA across the blood-brain barrier (BBB) by using the same system that delivers insulin to the brain. The ability to cross the BBB makes AGT-181 different from Aldurazyme for the treatments for MPS I.
What is the purpose of the Phase 1 clinical trial of AGT-181?
The purpose of this Phase 1 clinical trial is to determine a safe and well-tolerated dose of AGT-181 in adults with attenuated MPS I (Scheie and Hurler-Scheie).
Am I eligible to join the clinical trial?
The trial is open to adult patients (age 18 years or older) who have been diagnosed with Hurler-Scheie and Scheie syndromes. Patients must fall into one of the following groups:
Be currently receiving ERT and
Discontinue current ERT for the duration of a 13-week trial
Discontinue current ERT for at least six weeks before and during an eight-week
Have never received ERT or have not received ERT for at least 90 days, and have elevated mucopolysaccharides at least three times greater than normal at the beginning of the study. These patients will receive AGT-181 for eight weeks.
You can learn more about the study and enrollment process by calling the investigators at the study centers listed on using the identifier number NCT02371226, or by referring to the list available on the Breaking Barriers website. The study centers will evaluate your eligibility and review next steps with you.
Why aren’t patients with Hurler syndrome being enrolled into this trial?
This Phase 1 trial is designed to determine a safe and well-tolerated dose of AGT-181 in adults with MPS I. Fewer patients with Hurler syndrome, the most severe form of AGT-181, survive into adulthood. Pending the results of the Phase 1 trial, ArmaGen plans to conduct subsequent studies in a broader population of patients with MPS I, including those with Hurler syndrome.
What will I gain from participating in this study?
People choose whether or not to participate in clinical trials for various reasons. Participation in clinical trials can provide early access to treatments being studied for safety and effectiveness, expert medical care, and the opportunity to contribute to medical research and potentially help future generations of people with the disease being studied. Speak with your physician for guidance on whether to enroll in a trial.
How will AGT-181 be dosed in the trial?
You will receive weekly infusions of AGT-181 at assigned doses that range from 1.0 mg/kg for the first cohort (dose group) of patients enrolled or 3.0 mg/kg for the second cohort (dose group).
Potentially higher doses will be given, up to 9.0 mg/kg, if the 3.0 mg/kg does not appear to have an effect on urine disease markers called glycosoaminoglycans (GAGs) after 8 weeks. The drug solutions will be administered intravenously (IV) over a 3-hour period.
How will you determine whether AGT-181 is crossing the blood-brain barrier?
As part of this testing, study investigators will collect a sample of cerebrospinal fluid, which surrounds and protects the brain and spinal cord, from participants. This fluid will be tested to confirm whether there is a reduction in levels of glycosaminoglycans, or complex sugars that build up in the bodies of people living with MPS I.
How will my safety be ensured in the AGT-181-102?
To ensure the safety and welfare of patients, clinical trials are overseen by national health agencies. In addition, each clinical trial site appoints an Institutional Review Board (IRB) to review, monitor and approve medical research.
What kinds of side effects may be associated with AGT-181 treatment?
Patient safety is a priority for the sponsor of the study, the investigators and the patient community. Investigators will monitor for potential side effects of AGT-181 that may include urticaria (hives), rash, a general feeling of being unwell (malaise), shortness of breath, hypoxemia (abnormally low levels of oxygen in the blood), hypotension (abnormally low blood pressure), tachycardia (a rapid heartbeat), nausea, chills, fever or abdominal pain.
If you experience a side effect or adverse event during the clinical trial, the appropriate clinical treatment will be prescribed. You can choose to stop participating in the clinical trial at any time. If an adverse event is present when you withdraw from the study, then you will be re-evaluated within two weeks of withdrawal. If the adverse event has not resolved at that time, additional follow-up will be performed as appropriate.
Where can I find more information?
The trial is called the Breaking Barriers clinical trial of AGT-181-102. You can find more information on using the identifier number NCT02371226.
Where is the trial being conducted?
The trial will be conducted at specific academic centers specializing in MPS I located in the U.S.
Will ArmaGen cover transportation and housing for patients who live far from the site?
We are 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.
Study centers will provide more information on reimbursement of expenses, as well as contact information for travel agencies who can help with travel arrangements.
Is there a cost associated with participating in the trial? Will patients be paid to participate in the trial?
We understand that participating in a clinical trial is a significant commitment of time and, potentially, resources for families. There is no cost to participate in the trial and all tests will be provided to patients at no cost. Patients in the clinical trial will not be paid.
Who is sponsoring the clinical trial?
The trial is sponsored by ArmaGen, a privately held biotechnology company focused on developing revolutionary therapies for severe neurological disorders.