Mucopolysaccharidosis IPhase 1NCT02371226
Safety and Dose Ranging Study of Insulin Receptor MAb-IDUA Fusion Protein in Patients With MPS I
A Phase 1 study testing AGT-181 (HIRMAb-IDUA) in people with Mucopolysaccharidosis I, run by ArmaGen, Inc at 6 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucopolysaccharidosis I
- What is being tested?
- AGT-181 (HIRMAb-IDUA)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 6 sitesUnited States
- Study dates
- Jul 2015to 1 Feb 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Emory Healthcare
Decatur, Georgia, 30033
Children's Hospital Oakland
Oakland, California, 94609
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
University of Utah Hospital
Salt Lake City, Utah, 84132
About this study
Official title: A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Adult Patients With Mucopolysaccharidosis I (MPS I, Hurler Syndrome)
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.
- Conditions
- Mucopolysaccharidosis I
- Being tested
- AGT-181 (HIRMAb-IDUA)
- Keywords
- MPS I
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGT-181 (HIRMAb-IDUA)Drug
Also called fusion protein of monoclonal antibody to human insulin receptor fused to alpha-L-iduronidase
intravenous infusion over 3-4 hours
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: AGT-181 (HIRMAb-IDUA) |
| Cohort 2 | Experimental | 3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks Receives: Drug: AGT-181 (HIRMAb-IDUA) |
| Cohort 3 | Experimental | 6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks Receives: Drug: AGT-181 (HIRMAb-IDUA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events as a measure of safety and tolerability
Measured: 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)
Measured: 8 weeks
change in urinary or plasma glycosaminoglycans (GAGs)
Measured: 8 weeks
change in liver size
Measured: 8 weeks
change in spleen size
Measured: 8 weeks
change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study startJul 2015
- Primary completion23 Jan 2017
- Study completion1 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- ArmaGen, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patrice Rioux, MD PhD, Study director, ArmaGen, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02371226
- Sponsor's protocol ID
- AGT-181-102
- Status last verified
- Feb 2023
- First submitted
- 19 Feb 2015
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Adult Patients With Mucopolysaccharidosis I (MPS I, Hurler Syndrome)
- ClinicalTrials.gov ID
- NCT02371226
- Acronym / sponsor ID
- AGT-181-102
- Conditions
- Mucopolysaccharidosis I
- Keywords
- MPS I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- ArmaGen, IncIndustry (pharma, biotech, devices)
- Study start
- Jul 2015 (actual)
- Primary completion
- 23 Jan 2017 (actual)
- Study completion
- 1 Feb 2017 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: AGT-181 (HIRMAb-IDUA)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 |
| Cohort 2 | Experimental | Drug: AGT-181 (HIRMAb-IDUA)3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks |
| Cohort 3 | Experimental | Drug: AGT-181 (HIRMAb-IDUA)6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AGT-181 (HIRMAb-IDUA)Also: fusion protein of monoclonal antibody to human insulin receptor fused to alpha-L-iduronidaseintravenous infusion over 3-4 hours | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Number of participants with adverse events as a measure of safety and tolerability
Time frame: eight weeks
5 secondary outcomes
plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181)
Time frame: 8 weeks
change in urinary or plasma glycosaminoglycans (GAGs)
Time frame: 8 weeks
change in liver size
Time frame: 8 weeks
change in spleen size
Time frame: 8 weeks
change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
Related trials for Mucopolysaccharidosis I
Active, not recruitingObservational study
Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH.
Hematopoietic Cell Transplantation, Mucopolysaccharidosis Type I
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
Active, not recruitingPhase 1/2
An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis III-B
RecruitingPhase 2/3
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
MPS IIIA, Sanfilippo Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrice Rioux, MD PhD study director
ArmaGen, Inc
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AGT-181 (HIRMAb-IDUA) in people with Mucopolysaccharidosis I, run by ArmaGen, Inc at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events as a measure of safety and tolerability (time frame: eight weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.