Long-term Evaluation on Height and Weight in Patients With MPS II Who Started Treatment at < 6 Years of Age

NCT02455622 | Completed Phase 4 Results DMC

• 2 other identifiers: SHP-ELA-4012014-004804-31
• Study Type: interventional
• Target: 21
• Locations: 8 countries
• Sites: 8

Brief Summary

This long-term study will provide Elaprase treatment to children enrolled in this study and will utilize data from both enrolled patients and Hunter Outcome Survey (HOS) patient registry data to conduct the primary growth analysis to assess changes in height and weight in patients with Mucopolysaccharidosis II (Hunter syndrome) MPS II.

Conditions

Hunter Syndrome

Outcome Measures

Primary Outcomes (9)

• Height Overall

  The effect of treatment on growth evaluated in terms of height. As pre-specified in the statistical analysis plan (SAP), descriptive analysis for this outcome measure was planned for the Combined Set and HOS Untreated Set arms and the assessment for Primary Growth Analysis was considered for the Combined Set in comparison to the HOS Untreated Set. The Combined Set included treated participants enrolled in this study (prospective participants) as well as treated participants from the HOS registry.

  Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22

• Weight Overall

  The effect of treatment on growth was evaluated, in terms of weight. As pre-specified in the SAP, descriptive analysis for this outcome measure was planned for the Combined Set and HOS Untreated Set arms and the assessment for Primary Growth Analysis was considered for the Combined Set in comparison to the HOS Untreated Set. The Combined Set included treated participants enrolled in this study (prospective participants) as well as treated participants from the HOS registry.

  Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22

• Change From Baseline in Height Measured by Z-score

  Z-score(standard score) for height was calculated as number of standard deviations(SD) by which mean height of each arm was above/below the mean height of the reference population.Z-scores were calculated based on World Health Organization Drug Dictionary(WHO-DD) growth charts(for age less or equal to\[≤\] 24 months) \& Centers for Disease Control \& Prevention(CDC) growth charts(for age more than\[\>\]24 months) normal height-for-age data.Normal growth Z-score range: -1 to +1.Z-score:0 represents the reference mean \& 50th percentile.Z-score of more than or equal to(≥) +2 indicates above normal range \& taller than average \& Z-score ≤ -2 indicates shorter stature than average \& may indicate growth issues.Score is calculated as Z=(Actual value for participant in study-Mean value of healthy population)/(SD of healthy population).As per SAP,descriptive analysis was planned for Combined \& HOS Untreated Set arms, with Primary Growth Analysis assessed for Combined Set compared to HOS Untreated Set.

  Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22

• Change From Baseline in Weight Measured by Z-score

  Z-score (standard score) for weight was calculated as the number of SDs by which the mean weight of each arm was above or below the mean weight of the reference population. Z-scores were calculated based on WHO-DD growth charts (for age ≤ 24 months) \& CDC growth charts (for age \> 24 months) normal weight-for-age data. The normal range for growth Z score is defined as -1 to +1. Z-score: 0 represents reference population mean and the 50th percentile. Positive Z-score of ≥ +2 indicates above average weight (overweight). Negative Z-score of ≤ -2 indicates below average weight (underweight). The score is calculated as Z=(Actual value for participant in study-Mean value of healthy population)/(SD of healthy population). As per SAP, descriptive analysis was planned for Combined \& HOS Untreated Set arms, with Primary Growth Analysis assessed for Combined Set compared to HOS Untreated Set.

  Prospective participants: From Baseline through End-of-Study (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22

• Number of Participants With Clinical Significant Abnormal Neurological Examination

  A full physical examination will be performed with a thorough review of body systems. Physical examinations will include a review of the patient's general appearance, neurological examination, as well as evaluation of the body systems. Any abnormal change in findings will be recorded as an adverse event (AE).

  From Screening to End-of-Study (approximately 9.75 years)

• Number of Participants With Treatment-emergent Adverse Events (TEAE)

  An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered product-related. This includes an exacerbation of a pre-existing condition. A TEAE is defined as an AE with an onset that occurs after receiving study drug.

  From screening to End-of-Study (approximately 9.75 years)

• Number of Participants With Clinically Significant Abnormal Urinalysis Values

  Reported here is the number of participants with clinically significant abnormal values in urinalysis tests. Only tests with at least 1 participant with clinically significant abnormal values are reported. Participant was clinically significant abnormal if there was at least one abnormal and clinically significant post-baseline value.

  From screening to End-of-Study (approximately 9.75 years)

• Number of Participants With Clinically Significant Abnormal Serum Chemistry Values

  Reported here is the number of participants with clinically significant abnormal values in serum chemistry tests. Only tests with at least 1 participant with clinically significant abnormal values are reported. Participant was clinically significant abnormal if there was at least one abnormal and clinically significant post-baseline value.

  From screening to End-of-Study (approximately 9.75 years)

• Number of Participants With Clinically Significant Abnormal Hematology Values

  Reported here is the number of participants with clinically significant abnormal values in haematological tests. Only tests with at least 1 participant with clinically significant abnormal values are reported. Participant was clinically significant abnormal if there was at least one abnormal and clinically significant post-baseline value.

  From screening to End-of-Study (approximately 9.75 years)

Secondary Outcomes (12)

• Observed Value of Height Velocity From Baseline to End of Study

  Prospective participants: From Baseline till End-of-Study Treatment (approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22

• Observed Value of Weight Velocity From Baseline to End of Study

  Prospective participants: From Baseline till End-of- Study Treatment (Approximately 9.75 years); HOS participants followed up to a maximum of 9.5 years where participant data were accessed from the registry between the period of 08/01/07 to 02/06/22

• Percent Change From Baseline for Urinary Glycosaminoglycans (uGAG) Levels Normalized to Urine Creatinine

  Baseline to End-of-Study (Approximately 9.75 years)

• Normalized uGAG Divided by Upper Llimit of Normal for Age (uGAG/ULN) Every 12 Months

  Baseline to End-of-Study (Approximately 9.75 years)

• Liver Volume

  Baseline up to 24 Months

Study Arms (3)

Prospective Set

EXPERIMENTAL

Participants received IV infusions of Elaprase, once-weekly at a dose of 0.5 mg/kg. Thereafter, each enrolled participant continued receiving one infusion of Elaprase every week. They were be followed for a minimum of 5 years after initiation of Elaprase treatment, or until they reached their 10th birthday, whichever was longer.

Drug: Elaprase for intravenous (IV) infusion

Hunter Outcome Survey (HOS) Treated

NO INTERVENTION

Participants in the HOS patient registry, who were treated, were combined with the Prospective Set in the Primary Growth Analysis for this study using their height and weight data.

HOS Untreated

NO INTERVENTION

Participants in the HOS patient registry, we were not treated, were used as the comparator in the Primary Growth Analysis for this study using their height and weight data.

Interventions

Elaprase for intravenous (IV) infusion DRUG

Patients enrolled in this study will receive once-weekly IV infusions of Elaprase at a dose of 0.5 mg/kg and will be followed for a minimum of 5 years after initiation of Elaprase treatment, or until they reach their 10th birthday, whichever is longer.Height and weight data from HOS will be utilized in the Primary Growth Analysis for this study.

Also known as: Idursulfase

Prospective Set

Eligibility Criteria

• Age: Up to 5 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Group 1: Prospective Patient Group
• The patient is male.
• The patient is Elaprase-naïve at study entry.
• The patient must have a documented diagnosis of MPS II. Of the 3 criteria below, the combinations (3a AND 3b) or (3a AND 3c) will be accepted as diagnostic of MPS II:
• The patient has a deficiency in I2S enzyme activity of ≤10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on the reference laboratory's normal range). AND
• The patient has a documented mutation in the I2S gene. OR
• The patient has a normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on the normal range of measuring laboratory).
• The patient will be \<6 years of age at the start of Elaprase treatment.
• The patient, patient's parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form after all relevant aspects of the study have been explained and discussed. Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's assent, as relevant, must be obtained.
• The patient is male.
• The patient is enrolled in HOS.
• The patient was \<6 years of age at the start of Elaprase treatment.
• The patient received Elaprase weekly treatment for at least 5 years.
• The patient had a height assessment and a weight assessment documented within 3 months before or after Elaprase treatment start.
• The patient has had annual height and weight assessments from start of Elaprase through age 10 years.

You may not qualify if:

• Group 1: Prospective Patient Group
• The patient has received treatment with any investigational drug or device within the 30 days prior to study entry.
• The patient has received or is receiving treatment with idursulfase-IT.
• The patient has received growth hormones, a cord blood infusion, or a bone marrow transplant at any time.
• The patient has received blood product transfusions within 90 days prior to Screening.
• The patient is unable to comply with the protocol as determined by the Investigator.
• HOS patients that meet the following criteria are not eligible to be included into the Study SHP-ELA-401 Primary Growth Analysis:
• \. Patient was treated with growth hormone or other medications or interventions intended to promote growth in the time period covered by the analysis.

Sponsors & Collaborators

• Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (8)

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

Chicago, Illinois, 60611, United States

Location

Hospital Infantil Dr Robert Reid Cabral

Santo Domingo, 10101, Dominican Republic

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

Location

Philippine General Hospital

Manila, 1000, Philippines

Location

Mother and Child Health Care Institute of Serbia Dr Vukan Cupic

Belgrade, 11000, Serbia

Location

Chulalongkorn University

Bangkok, 10330, Thailand

Location

National Pediatrics Hospital

Hanoi, Vietnam

Location

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

MeSH Terms

Conditions

Mucopolysaccharidosis II

Interventions

idursulfase

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 28, 2015
• Study Start: October 28, 2015
• Primary Completion: July 29, 2025
• Study Completion: July 29, 2025
• Last Updated: April 2, 2026
• Results First Posted: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

DO (1); TH (1); US (1); PH (1); MY (1); DE (1); VN (1); SE (1)