Hunter SyndromePhase 4NCT00607386

Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Therapy

A Phase 4 study testing Idursulfase in people with Hunter Syndrome and Mucopolysaccharidosis II, run by Shire at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The objective of this study is to determine the safety of once weekly dosing of idursulfase 0.5 mg/kg administered by intravenous (IV) infusion for male Hunter syndrome patients ≤ 5 years old. Read more about this study

Who is it for?: Ages Up to 5 years, men only
Conditions the study is for: Hunter Syndrome, Mucopolysaccharidosis II, MPS II
What is being tested?: Idursulfase
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 3 sitesin 3 countries
Study dates: 31 Dec 2007to 8 Jul 2011
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 Up to 5 years
Men only
No healthy volunteers
Child

Who may be able to join

The patient has a diagnosis of Hunter syndrome based upon biochemical criteria either documented in their medical history or established at Screening:
A deficiency in iduronate-2-sulfatase (I2S) enzyme activity of ≤ 10 % of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory)
AND
A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
The patient is 5 years of age and under.
The patient is male.
The patient's parent(s), or patient's legal guardian must have voluntarily signed an Institutional Review Board approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient's parent(s), or the patient's legal guardian.

Who cannot join

The patient has received treatment with another investigational therapy within 30 days prior to enrollment.
The patient has clinically relevant medical condition(s) making implementation of the protocol difficult.
The patient has previously received idursulfase.
The patient has known hypersensitivity to any of the components of idursulfase.
The patient has had a tracheostomy.

Trial locations and contacts

3 sites in 3 countries.

Country

City, postcode or hospital

3 sites in 3 countries

Brazil1 site

Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
Porto Alegre, Rio Grande do Sul, 90035-903

Other trials in Brazil

Poland1 site

Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii
Warsaw, 04-730

Other trials in Poland

Taiwan1 site

National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics
Taipei, 10016

Other trials in Taiwan

About this study

Official title: A Multi-Center, Open-Label Study Evaluating Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Enzyme Replacement Therapy

The objective of this study is to determine the safety of once weekly dosing of idursulfase 0.5 mg/kg administered by intravenous (IV) infusion for male Hunter syndrome patients ≤ 5 years old.

Read the detailed description

This study will provide a basis for evaluating the safety of idursulfase administered to Hunter syndrome patients who are ≤ 5 years old. Additionally, this study will provide a basis for evaluating the idursulfase single- and repeated-dose pharmacokinetic profiles as well as the pharmacodynamic effect (as measured by urinary GAG excretion) in this pediatric population. Additional exploratory measures will include abdominal ultrasound measurements of liver and spleen volumes, assessments of growth with comparisons to normal population growth data, assessments of annualized growth velocity, assessments of routine developmental milestones using the Denver II, and assessments of clinical events, including the first occurrence of certain hearing-related events (e.g., hearing loss, otitis media), respiratory-related events (e.g., upper and lower respiratory infections), and specific surgical procedures (e.g., adenoidectomy, placement of PE tubes).

All patients in this open-label study will receive once-weekly infusions of idursulfase at a dose of 0.5 mg/kg.

Conditions: Hunter Syndrome, Mucopolysaccharidosis II, MPS II
Being tested: Idursulfase
Keywords: Hunter syndrome, hunters syndrome, hunter's syndrome, hunter disease, hunters disease, hunter's disease, MPS II, MPSII, MPS2, MPS 2, mucopolysaccharides, lysosomal storage disease, lysosomal storage disorder, chronic ear infection, enlarged adenoids, mps symptoms, mps diagnosis, mps ii therapy, MPS II treatment, ert treatment
Medical subject headings: Mucopolysaccharidosis II, Sudden Infant Death, Lysosomal Storage Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IdursulfaseBiological
Also called Elaprase
Solution for intravenous infusion, 0.5 mg/kg weekly

Study groups in NCT00607386
Study group	Role	What they receive
Idursulfase	Other	Open-label treatment with idursulfase Receives: Biological: Idursulfase

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety Evaluation
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with AEs occurred after start of study treatment until 30 days after the last infusion of idursulfase, were reported.
Measured: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks

Secondary outcomes (9)

Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels
Analysis of urinary GAG levels was performed at baseline, Week 18, Week 36, and Week 53 as an assessment of the pharmacodynamic effects of Elaprase (idursulfase).
Measured: Baseline, Weeks 18, 36 and 53
Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)
Measured: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)
Measured: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to the Final Time Point With a Concentration of at Least Lower Limit of Quantitation (AUClast)
Measured: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)
Measured: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)
t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in minutes and derived from the terminal slope of the concentration versus time curve.
Measured: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)
MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes.
Measured: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Measured: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steadystate.
Measured: Weeks 1 and 27

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Dec 20078 Jul 2011

First posted5 Feb 2008 (estimated)
Study start31 Dec 2007
Primary completion8 Jul 2011
Study completion8 Jul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Hunter SyndromeStudies 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 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00607386
Sponsor's protocol ID: HGT-ELA-038
Other IDs: 2007-006044-22
Status last verified: May 2021
First submitted: 22 Jan 2008
Last updated: 8 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20.
PubMed 17185020
Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. doi: 10.1097/01.gim.0000232477.37660.fb.
PubMed 16912578
Pano A, Barbier AJ, Bielefeld B, Whiteman DA, Amato DA. Immunogenicity of idursulfase and clinical outcomes in very young patients (16 months to 7.5 years) with mucopolysaccharidosis II (Hunter syndrome). Orphanet J Rare Dis. 2015 Apr 24;10:50. doi: 10.1186/s13023-015-0265-2.
PubMed 25902842

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
Enrolling by invitationPhase 2/3
An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Mucopolysaccharidosis II
Active, not recruitingPhase 3
A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)
Mucopolysaccharidosis II
Active, not recruitingPhase 2/3
A Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
Mucopolysaccharidosis Type II, Metabolic Diseases
Active, not recruitingPhase 2/3
A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)
Mucopolysaccharidosis II

All Hunter Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Center, Open-Label Study Evaluating Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Enzyme Replacement Therapy
ClinicalTrials.gov ID: NCT00607386
Acronym / sponsor ID: HGT-ELA-038
Conditions: Hunter Syndrome, Mucopolysaccharidosis II, MPS II
Keywords: Hunter syndrome, hunters syndrome, hunter's syndrome, hunter disease, hunters disease, hunter's disease, MPS II, MPSII
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Collaborators: Covance, PharmaNet, PRA Health Sciences
Study start: 31 Dec 2007 (actual)
Primary completion: 8 Jul 2011 (actual)
Study completion: 8 Jul 2011 (actual)
First posted: 5 Feb 2008 (estimated)
Results: Posted 7 Nov 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The objective of this study is to determine the safety of once weekly dosing of idursulfase 0.5 mg/kg administered by intravenous (IV) infusion for male Hunter syndrome patients ≤ 5 years old.

Detailed description

All patients in this open-label study will receive once-weekly infusions of idursulfase at a dose of 0.5 mg/kg.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Idursulfase	Other	Biological: IdursulfaseOpen-label treatment with idursulfase

Who may qualify

Ages: Up to 5 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

The patient has a diagnosis of Hunter syndrome based upon biochemical criteria either documented in their medical history or established at Screening:
AND
The patient is 5 years of age and under.
The patient is male.
The patient's parent(s), or patient's legal guardian must have voluntarily signed an Institutional Review Board approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient's parent(s), or the patient's legal guardian.

Key exclusion criteria (5 listed)

The patient has received treatment with another investigational therapy within 30 days prior to enrollment.
The patient has clinically relevant medical condition(s) making implementation of the protocol difficult.
The patient has previously received idursulfase.
The patient has known hypersensitivity to any of the components of idursulfase.
The patient has had a tracheostomy.

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
IdursulfaseAlso: ElapraseSolution for intravenous infusion, 0.5 mg/kg weekly	Biological	Idursulfase

Primary outcome

Safety Evaluation
Time frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with AEs occurred after start of study treatment until 30 days after the last infusion of idursulfase, were reported.

9 secondary outcomes

Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels
Time frame: Baseline, Weeks 18, 36 and 53
Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)
Time frame: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)
Time frame: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to the Final Time Point With a Concentration of at Least Lower Limit of Quantitation (AUClast)
Time frame: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)
Time frame: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)
Time frame: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)
Time frame: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)
Time frame: Weeks 1 and 27
Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)
Time frame: Weeks 1 and 27

Results and safety

Results posted to the registry on 7 Nov 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Idursulfase	28	27

Primary outcome: Safety Evaluation

Time frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks. Number. Unit: participants

Measure	Idursulfase n = 28
Experienced at least one adverse event (AE)	28
Deaths	0
Discontinued due to an AE	0
Experienced at least one drug-related AE	16
Experienced at least one serious AE (SAE)	13
Experienced at least one severe AE	2
Experienced at least one infusion-related AE	16

Population analysed: Safety population was defined as all enrolled participants who received at least one study dose (or any portion of a dose) of idursulfase.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks. Other adverse events reported at 3.57% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Idursulfase	13 of 28 (46.4%)	28 of 28 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17185020Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20.
Background: PubMed 16912578Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. doi: 10.1097/01.gim.0000232477.37660.fb.
Results publication: PubMed 25902842Pano A, Barbier AJ, Bielefeld B, Whiteman DA, Amato DA. Immunogenicity of idursulfase and clinical outcomes in very young patients (16 months to 7.5 years) with mucopolysaccharidosis II (Hunter syndrome). Orphanet J Rare Dis. 2015 Apr 24;10:50. doi: 10.1186/s13023-015-0265-2.

Related trials for Hunter Syndrome

Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
Enrolling by invitationPhase 2/3
An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Mucopolysaccharidosis II
Active, not recruitingPhase 3
A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)
Mucopolysaccharidosis II
Active, not recruitingPhase 2/3
A Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
Mucopolysaccharidosis Type II, Metabolic Diseases
Active, not recruitingPhase 2/3
A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)
Mucopolysaccharidosis II

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.

Study Director study director

Takeda

3 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Idursulfase in people with Hunter Syndrome and Mucopolysaccharidosis II, run by Shire at 3 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 7 inclusion and 5 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 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Brazil, Poland, Taiwan. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Safety Evaluation (time frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00607386, which also lists 3 linked publications.

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 8 Jun 2021.