NCT02371226

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jul 2015

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 19, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 25, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

July 1, 2015

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 23, 2017

Completed
9 days until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2017

Completed
Last Updated

February 21, 2023

Status Verified

February 1, 2023

Enrollment Period

1.6 years

First QC Date

February 19, 2015

Last Update Submit

February 19, 2023

Conditions

Mucopolysaccharidosis I

Keywords

MPS I

Outcome Measures

Primary Outcomes (1)

  • Number of participants with adverse events as a measure of safety and tolerability

    eight weeks

Secondary Outcomes (5)

  • 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

Study Arms (3)

Cohort 1

EXPERIMENTAL

1 mg/kg AGT-181 (fusion protein of anti-human insulin receptor monoclonal antibody and alpha-L-iduronidase; HIRMAb-IDUA) administered once weekly x 8 weeks

Drug: AGT-181 (HIRMAb-IDUA)

Cohort 2

EXPERIMENTAL

3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks

Drug: AGT-181 (HIRMAb-IDUA)

Cohort 3

EXPERIMENTAL

6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks

Drug: AGT-181 (HIRMAb-IDUA)

Interventions

AGT-181 (HIRMAb-IDUA)DRUG

intravenous infusion over 3-4 hours

Also known as: fusion protein of monoclonal antibody to human insulin receptor fused to alpha-L-iduronidase
Cohort 1Cohort 2Cohort 3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Emory Healthcare

Decatur, Georgia, 30033, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I

Interventions

valanafusp alpha

Condition Hierarchy (Ancestors)

MucopolysaccharidosesCarbohydrate Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLysosomal Storage DiseasesMucinosesConnective Tissue DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Patrice Rioux, MD PhD

    ArmaGen, Inc

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Masking Details
Open Label
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 19, 2015

First Posted

February 25, 2015

Study Start

July 1, 2015

Primary Completion

January 23, 2017

Study Completion

February 1, 2017

Last Updated

February 21, 2023

Record last verified: 2023-02

Locations

US(6)