Mucopolysaccharidosis IIPhase 1NCT02262338
Safety and Dose Ranging Study of Insulin Receptor MoAb-IDS Fusion Protein in Patients With Hunter Syndrome
A Phase 1 study testing AGT-182 in people with Mucopolysaccharidosis II, run by ArmaGen, Inc at 5 sites in 3 countries.
Trial summary
AGT-182 is a fusion protein containing idursulfase 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Mucopolysaccharidosis II
- What is being tested?
- AGT-182
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Apr 2015to 27 Mar 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male age 18 years or older
- Diagnosis of Hunter Syndrome (documented fibroblast or leukocyte IDS enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory - or any level of enzyme deficiency together with the presence of a pathogenic mutation in the IDS gene - and documentation of normal enzymatic activity of at least 1 other sulfatase.)
- Must fall into one of the following groups:
- currently receiving standard enzyme replacement therapy (ERT) and be willing to discontinue it for the study duration, taking AGT-182 instead
- have not received standard ERT for at least 3 months and have elevated uGAGs of at least 3.5 fold above age-related normals at study screening
- have never received ERT
- Voluntary written consent
- Sexually mature males must be advised to use a medically accepted method of contraception throughout the study.
Who cannot join
- Refusal to complete screening/baseline evaluations
- Receipt of an investigational drug within the prior 90 days
- Any medical condition or other circumstances that may significantly interfere with study compliance
- Clinically significant spinal cord compression, evidence of cervical instability
- Known hypersensitivity to idursulfase or any of the components of AGT-182
- Known to be nonresponsive to standard ERT treatment (i.e., high uGAG values despite taking full dose standard ERT)
- History of diabetes mellitus or hypoglycemia
- Contraindication to lumbar puncture, if the patient agrees to this optional assessment
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States3 sites
Emory University
Decatur, Georgia, 30033
Children's Hospital Oakland
Oakland, California, 94609
Children's Hospital of Orange County
Orange, California, 92868
Philippines1 site
Institute of Human Genetics, National Inst of Health, University of the Philippines
Manila
About this study
Official title: A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Iduronate 2-Sulfatase (IDS) Fusion Protein, AGT-182 in Adult Patients With Mucopolysaccharidosis II (MPS II, Hunter Syndrome)
AGT-182 is a fusion protein containing idursulfase 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.
Read the detailed description
This is a sequential, open-label, dose escalation, multi-dose study in adults with Hunter syndrome. Two dose levels, assuming tolerability, are planned sequentially, with safety data from the previous cohort being reviewed prior to escalation to the next higher dose cohort. Subjects will receive weekly doses of AGT-182 for 8 weeks if ERT-naive or agreeing to a 6-week ERT washout, or for 13 weeks if currently taking ERT and not agreeing to washout.
- Conditions
- Mucopolysaccharidosis II
- Being tested
- AGT-182
- Keywords
- MPS II, Hunter Syndrome
- Medical subject headings
- Mucopolysaccharidosis II, Sudden Infant Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGT-182Drug
Recombinant HIRMAb-IDS
| Study group | Role | What they receive |
|---|---|---|
| Treated subjects | Experimental | AGT-182 solution for infusion will be administered intravenously at doses of 1.0 mg/kg or 3.0 mg/kg weekly for 8-13 weeks. Receives: Drug: AGT-182 |
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: 8 weeks (ERT-naive) or 13 weeks (ERT)
Secondary outcomes (4)
plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182)
Measured: 8 weeks (ERT-naive) or 13 weeks (ERT)
change in urinary or plasma glycosaminoglycans (GAGs)
Measured: 8 weeks (ERT-naive) or 13 weeks (ERT)
change in liver or spleen size
Measured: 8 weeks (ERT-naive) or 13 weeks (ERT)
change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)
Measured: 8 weeks (ERT-naive) or 13 weeks (ERT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2014 (estimated)
- Study startApr 2015
- Primary completion27 Mar 2017
- Study completion27 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis IIStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 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
- NCT02262338
- Sponsor's protocol ID
- AGT-182-101
- Status last verified
- Sep 2018
- First submitted
- 2 Oct 2014
- Last updated
- 18 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. 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 Iduronate 2-Sulfatase (IDS) Fusion Protein, AGT-182 in Adult Patients With Mucopolysaccharidosis II (MPS II, Hunter Syndrome)
- ClinicalTrials.gov ID
- NCT02262338
- Acronym / sponsor ID
- AGT-182-101
- Conditions
- Mucopolysaccharidosis II
- Keywords
- MPS II, Hunter Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- ArmaGen, IncIndustry (pharma, biotech, devices)
- Study start
- Apr 2015 (actual)
- Primary completion
- 27 Mar 2017 (actual)
- Study completion
- 27 Mar 2017 (actual)
- First posted
- 13 Oct 2014 (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-182 is a fusion protein containing idursulfase 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.
Detailed description
This is a sequential, open-label, dose escalation, multi-dose study in adults with Hunter syndrome. Two dose levels, assuming tolerability, are planned sequentially, with safety data from the previous cohort being reviewed prior to escalation to the next higher dose cohort. Subjects will receive weekly doses of AGT-182 for 8 weeks if ERT-naive or agreeing to a 6-week ERT washout, or for 13 weeks if currently taking ERT and not agreeing to washout.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treated subjects | Experimental | Drug: AGT-182AGT-182 solution for infusion will be administered intravenously at doses of 1.0 mg/kg or 3.0 mg/kg weekly for 8-13 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male age 18 years or older
- Diagnosis of Hunter Syndrome (documented fibroblast or leukocyte IDS enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory - or any level of enzyme deficiency together with the presence of a pathogenic mutation in the IDS gene - and documentation of normal enzymatic activity of at least 1 other sulfatase.)
- Must fall into one of the following groups:
- Voluntary written consent
- Sexually mature males must be advised to use a medically accepted method of contraception throughout the study.
Key exclusion criteria (8 listed)
- Refusal to complete screening/baseline evaluations
- Receipt of an investigational drug within the prior 90 days
- Any medical condition or other circumstances that may significantly interfere with study compliance
- Clinically significant spinal cord compression, evidence of cervical instability
- Known hypersensitivity to idursulfase or any of the components of AGT-182
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-182Recombinant HIRMAb-IDS | Drug | Treated subjects |
Primary outcome
number of participants with adverse events as a measure of safety and tolerability
Time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
4 secondary outcomes
plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182)
Time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
change in urinary or plasma glycosaminoglycans (GAGs)
Time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
change in liver or spleen size
Time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)
Time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
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 18 Sep 2018.
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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
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AGT-182 in people with Mucopolysaccharidosis II, run by ArmaGen, Inc at 5 sites in 3 countries.
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 8 inclusion and 8 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 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Germany, Philippines. 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: 8 weeks (ERT-naive) or 13 weeks (ERT)). 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 18 Sep 2018.