Safety and Dose Ranging Study of Human Insulin Receptor MAb-IDUA Fusion Protein in Adults and Children With MPS I

• Register: ClinicalTrials.gov
• Last refreshed on: 27 March 2023
• Main ID: NCT03053089
• Date of registration: 09/02/2017
• Prospective Registration: No
• Primary sponsor: ArmaGen, Inc
• Public title: Safety and Dose Ranging Study of Human Insulin Receptor MAb-IDUA Fusion Protein in Adults and Children With MPS I
• Scientific title: A Two-Stage, Phase 1/2, Open-Label Study of the Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Patients With Mucopolysaccharidosis I (MPS I, Hurler Syndrome)
• Date of first enrolment: October 2015
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03053089
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Brazil

Contacts

• Name: Patrice P Rioux, MD PhD
• Affiliation: ArmaGen, Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written consent and assent as required

- Diagnosis of MPS 1 confirmed by clinical signs and symptoms, documented fibroblast or
leukocyte IDUA enzyme activity of less than 10% the lower limit of normal

- Female patients must not be pregnant, willing to utilize appropriate birth control
methods and undergo pregnancy testing during the study

- if taking standard ERT, must be willing to discontinue for 1 week prior to dosing and
for the study duration

Additional Inclusion Criteria, Stage 1:

- 18 years of age or older

- must have a diagnosis of Hurler-Scheie or Scheie syndrome

Additional Inclusion Criteria, Stage 2:

- 2 years of age or older (and less than 18)

- must be willing to undergo CNS testing, including assessment of CSF via lumbar
puncture, MRI scans and neurocognitive testing

- must have evidence of Hurler-Scheie or Scheie with CNS involvement, as evidence by:

- score of 1 to 3 standard deviations below mean on IQ testing (i.e. IQ=55 or more) or
in one domain of neuropsychological function (language, memory, non-verbal ability) OR

- documented historical evidence of a decline greater than 1 standard deviation on
sequential testing, OR

- score between 0.75 and 1 standard deviation below the mean, AND cognitive deficit
affects daily performance

Exclusion Criteria:

- Refusal to complete all assessments

- Pregnant or Lactating

- Received investigational drug within 1 year prior to study enrollment

- Medical condition or extenuating circumstance that, in the opinion of the
investigator, may interfere with study compliance

- CSF pressure greater than 25 cm H20 (18 mm Hg)

- Known hypersensitivity to alpha-L-iduronidase (IDUA/Aldurazyme) or any
components/excipients found in AGT-181

- Previous successful (engrafted) hematopoietic stem cell transplantation which has
resulted in normalization of urinary glycosaminoglycans (GAGs); or major organ
transplantation

- Clinically significant spinal cord compression or evidence of cervical instability
(i.e. expected to require intervention during study participation)

- History of diabetes mellitus or hypoglycemia

Additional Exclusion Criteria, Stage 2:

- Has ventriculoperitoneal shunt

- IQ below 55

- Previously received AGT-181 in Stage 1 of the study



Age minimum: 2 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Mucopolysaccharidosis I

Intervention(s)

Drug: AGT-181

Primary Outcome(s)

Stage 1: number of patients with adverse events as a measure of safety and tolerability of a single dose [Time Frame: 4 weeks]

Stage 2: number of patients with adverse events as a measure of safety and tolerability of repeat weekly doses [Time Frame: 26 weeks]

Secondary Outcome(s)

change in functional capacity (6-minute walk test) or lung function (forced vital capacity) [Time Frame: 26 weeks]

change in shoulder range of motion (ROM) [Time Frame: 26 weeks]

change in liver and/or spleen volume (measured by MRI) [Time Frame: 26 weeks]

change in total urinary glycosaminoglycans (GAGs) [Time Frame: 26 weeks]

PK parameters (maximal concentration, half-life, AUC, distribution and clearance) of AGT-181 [Time Frame: 26 weeks]

Secondary ID(s)

AGT-181-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors