Back to results

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

Primary Purpose

Hunter Syndrome, Mucopolysaccharidosis II, MPS II

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Idursulfase

About this trial

This is an interventional treatment trial for Hunter Syndrome focused on measuring 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, elaprase, idursulfase, iduronate sulfatase, iduronate 2 sulfatase, enzyme replacement therapy, hunter syndrome treatment, hunter's syndrome treatment, hunter syndrome therapy, hunter's disease treatment, mps society

Eligibility Criteria

undefined - 5 Years (Child)MaleDoes not accept healthy volunteers

Inclusion Criteria:

The patient has a diagnosis of Hunter syndrome based upon biochemical criteria either documented in their medical history or established at Screening:
1. 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
2. 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.

Exclusion Criteria:

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.

Sites / Locations

Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii
National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Idursulfase

Arm Description

Open-label treatment with idursulfase

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)

Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)

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)

Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)

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.

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.

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.

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.

Full Information

NCT ID

NCT00607386

First Posted

January 22, 2008

Last Updated

May 14, 2021

Sponsor

Shire

Collaborators

Covance, PharmaNet, PRA Health Sciences

1. Study Identification

Unique Protocol Identification Number

NCT00607386

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

December 31, 2007 (Actual)

Primary Completion Date

July 8, 2011 (Actual)

Study Completion Date

July 8, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shire

Collaborators

Covance, PharmaNet, PRA Health Sciences

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hunter Syndrome, Mucopolysaccharidosis II, MPS II

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, elaprase, idursulfase, iduronate sulfatase, iduronate 2 sulfatase, enzyme replacement therapy, hunter syndrome treatment, hunter's syndrome treatment, hunter syndrome therapy, hunter's disease treatment, mps society

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Idursulfase

Arm Type

Other

Arm Description

Open-label treatment with idursulfase

Intervention Type

Biological

Intervention Name(s)

Idursulfase

Other Intervention Name(s)

Elaprase

Intervention Description

Solution for intravenous infusion, 0.5 mg/kg weekly

Primary Outcome Measure Information:

Title

Safety Evaluation

Description

Time Frame

From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks

Secondary Outcome Measure Information:

Title

Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels

Description

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).

Time Frame

Baseline, Weeks 18, 36 and 53

Title

Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)

Time Frame

Weeks 1 and 27

Title

Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)

Time Frame

Weeks 1 and 27

Title

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

Title

Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)

Time Frame

Weeks 1 and 27

Title

Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)

Description

Time Frame

Weeks 1 and 27

Title

Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)

Description

MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes.

Time Frame

Weeks 1 and 27

Title

Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)

Description

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Time Frame

Weeks 1 and 27

Title

Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)

Description

Time Frame

Weeks 1 and 27

10. Eligibility

Sex

Male

Maximum Age & Unit of Time

5 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica

City

Porto Alegre

State/Province

ZIP/Postal Code

90035-903

Country

Brazil

Facility Name

Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii

City

Warsaw

ZIP/Postal Code

04-730

Country

Poland

Facility Name

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

City

Taipei

ZIP/Postal Code

10016

Country

Taiwan

12. IPD Sharing Statement

Citations:

PubMed Identifier

17185020

Citation

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.

Results Reference

background

PubMed Identifier

16912578

Citation

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. Erratum In: Genet Med. 2006 Sep;8(9):599. Wendt, Suzanne [corrected to Wendt, Susanne]; Puga, Antonio [corrected to Puga, Ana Cristina]; Conway, Ann Marie [corrected to Conway, Anne Marie].

Results Reference

background

PubMed Identifier

25902842

Citation

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.

Results Reference

result

Learn more about this trial

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

We'll reach out to this number within 24 hrs