Mucopolysaccharidosis I
Conditions
Keywords
MPS I
Brief summary
AGT-181 is a fusion protein containing alpha-L-Iduronidase that is intended to deliver the enzyme peripherally and to the brain, when administered intravenously. This study is a safety and dose ranging study to obtain safety and exposure data, as well as information on the biological activity of the investigational drug.
Interventions
DRUGAGT-181 (HIRMAb-IDUA)
intravenous infusion over 3-4 hours
Sponsors
ArmaGen, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male age 18 years or older * Diagnosis of MPS I (documented fibroblast or leukocyte IDUA enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory) * Voluntary written consent by patient or legally responsible representative * All women of childbearing potential and sexually mature males must be advised to use a medically accepted method of contraception throughout the study. * Negative pregnancy test (females) * Must not have received ERT for at least 6 weeks prior to AGT-181 treatment * Must have elevated urinary GAGs if no ERT has been received in the prior 3 months
Exclusion criteria
* Refusal to complete baseline evaluations. * Any medical condition or other circumstances that may significantly interfere with study compliance * Receipt of an investigational drug within the prior 90 days * History of diabetes mellitus or hypoglycemia * Clinically significant spinal cord compression, evidence of cervical instability. * Known hypersensitivity to alpha-L-iduronidase or any of the components of AGT-181. * Known to be nonresponsive to standard ERT treatment. * Previously successful (engrafted) hematopoietic stem cell transplantation that resulted in normalization of urinary GAGs. * Contraindication for lumbar puncture
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events as a measure of safety and tolerability | eight weeks |
Secondary
| Measure | Time frame |
|---|---|
| plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181) | 8 weeks |
| change in urinary or plasma glycosaminoglycans (GAGs) | 8 weeks |
| change in liver size | 8 weeks |
| change in spleen size | 8 weeks |
| change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid | 8 weeks |
Countries
United States
Outcome results
None listed