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NCT Number: NCT02455622

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

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.

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Key information

Conditions

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

Age range

Up to 5 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 4

Primary location

Hospital Infantil Dr Robert Reid Cabral, Santo Domingo, Dominican Republic

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Group 2: Retrospective Data Inclusion Criteria:

Retrospective Patient Group patients will be enrolled in HOS and not Study SHP-ELA-401; however, their growth data may be included in the analysis for Study SHP-ELA-401 if the following data inclusion criteria are met.

  • 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.
  • The patient, patient's parent(s), or legally authorized guardian(s) agree(s) to data collection.
  • The patient, patient's parent(s), or legally authorized guardian(s) must have signed an IRB/IEC-approved informed consent form after all relevant aspects of the HOS 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.

Exclusion criteria

  • 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.

Group 2: Retrospective Data Exclusion Criteria:

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.

Treatment and study plan

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.

Other names: Idursulfase

Primary outcomes

  1. Height Overall

    Time frame: 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

    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.

  2. Weight Overall

    Time frame: 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

    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.

  3. Change From Baseline in Height Measured by Z-score

    Time frame: 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

    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.

  4. Change From Baseline in Weight Measured by Z-score

    Time frame: 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

    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.

  5. Number of Participants With Clinical Significant Abnormal Neurological Examination

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

    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).

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

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

    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.

  7. Number of Participants With Clinically Significant Abnormal Urinalysis Values

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

    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.

  8. Number of Participants With Clinically Significant Abnormal Serum Chemistry Values

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

    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.

  9. Number of Participants With Clinically Significant Abnormal Hematology Values

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

    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.

Secondary outcomes

  1. Observed Value of Height Velocity From Baseline to End of Study

    Time frame: 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

    Height velocity was calculated as the difference in height, divided by the difference in age between consecutive study visits.

  2. Observed Value of Weight Velocity From Baseline to End of Study

    Time frame: 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

    Weight velocity was be calculated as the difference in weight, divided by the difference in age between consecutive study visits.

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

    Time frame: Baseline to End-of-Study (Approximately 9.75 years)

    Urinary GAG levels were normalized to urine creatinine (normalized uGAG) and reported as mg uGAG/ millimoles (mmol) creatinine.

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

    Time frame: Baseline to End-of-Study (Approximately 9.75 years)

    Normalized uGAG was divided by the upper limit of normal for age (uGAG/ULN), where the ULN for uGAG was obtained from Mayo Clinic.

  5. Liver Volume

    Time frame: Baseline up to 24 Months

    Liver volume was assessed using abdominal ultrasonography.

  6. Spleen Volume

    Time frame: Baseline up to 24 Months

    Spleen volume was assessed using abdominal ultrasonography.

  7. Joint Mobility, as Measured by Joint Range of Motion (JROM) Scores, Including Upper-Limb and Lower-Limb Joint Scores

    Time frame: From Baseline to End-of-Study (approximately 9.75 years)

    Global JROM (% normal range of motion [ROM]) is average of 11 ratios multiplied by 100. Ratios are Left/Right means of passive ROM in Shoulder (Flexion [flex]/Extension [ext], Abduction, Internal/External Rotation), Elbow (flex/ext), Wrist (flex/ext), Index Finger (flex/ext [Combined Metacarpophalangeal joint, Proximal interphalangeal joint, Distal interphalangeal joint motion]), Hip (flex/ext, Abduction, Internal/External Rotation), Knee(flex/ext) & Ankle (Dorsiflexion) divided by normal range (reference: American Academy of Orthopedic Surgeons and American Medical Association). For reported values of upper limb (UL) & lower limb (LL) scores, UL score is average of 3 joint scores in UL (shoulder-elbow-wrist) & LL score is average of 3 joint scores in LL (hip-knee-ankle). Joint motion (in degrees) was averaged across both sides, divided by normal value & multiplied by 100 to yield a percent score. Score >100% occurs when measured joint motion exceeds normal reference values.

  8. Distance Walked, as Measured by Six Minute Walk Test (6MWT)

    Time frame: From Baseline to End-of-Study (approximately 9.75 years)

    The 6MWT was conducted according to the American Thoracic Society guidelines for the 6MWT in participants who were able to walk. The distance achieved in meters was recorded.

  9. Quality of Life, as Measured by Hunter-Syndrome Functional Outcome in Clinical Understanding Scale (HS-FOCUS)

    Time frame: Baseline to End-of-Study (Approximately 9.75 years)

    The participant's QoL was assessed using the HS-FOCUS (shortened version) questionnaire. The HS-FOCUS (shortened version) questionnaire has 5 function domains (walking/standing, grip/reach, schooling/work, activities, and breathing). The scale of the 5 function domains ranges from 0 to 3, with a 3-score denoting highest disability: 0: with no difficulty;1: with some difficulty; 2: with much difficulty; 3: unable to do; Missing: Does not apply. The response option "Does not apply" is treated as "missing" with no score, the same as if the item had not been completed in the questionnaire. Higher scores indicate worse functional outcomes/greater disability.

  10. Impact of Illness on Ability to Function in Daily Life, as Measured by Childhood Health Assessment Questionnaire (CHAQ Parent Report)

    Time frame: Baseline to End-of-Study (approximately 9.75 years)

    Impact on ability to function in daily life was measured by the CHAQ (Parent Report). The CHAQ includes 30 items measured on a scale of 0 to 3: 0=without any difficulty; 1=with some difficulty; 2=with much difficulty; 3=Unable to do; Missing: Does not apply. It evaluates functional abilities across 8 domains (dressing, hygiene, arising, eating, walking, reach, grip and activities). The result is referred as Disability Index. The highest scoring item in each category determines the score for that category with higher scores indicating worse functioning/higher disability. The Discomfort Index and Health Status Index are measured on separate 15 cm scales. The distance from the left end of the scale to the respondent's mark is measured and multiplied by 0.2 to calculate the score (range 0-3). Discomfort and Health Status Index scores were rescaled to 0-100 scales. Higher scores indicate greater discomfort/worse health status.

  11. Adaptive Behavior, as Measured by the Vineland Adaptive Behavior Scales (VABS II)

    Time frame: Baseline to End-of-Study (approximately 9.75 years)

    Adaptive behavior was assessed using parent/caregiver report on the VABS-II, a standardized norm-referenced tool to evaluate adaptive behavior for ages 0-90.VABS-II has 1 composite score(Adaptive Behavior Composite [ABC]), reflecting overall adaptive ability.ABC comprises 4 domain scores in participants <7years old(Communication,Daily Living Skills,Socialization,& Motor Skills)& 3 domain scores in participants ≥7years of age(Communication,Daily Living Skills,& Socialization).ABC standard score is derived from domain standard scores per VABS-II manual(not a simple sum/average of the reported standard scores).Domain scores are standard scores derived from combination of 11 subdomain scores according to VABS-II scoring rules/manual.Scale for ABC & domain standard scores ranges between 20 & 160.ABC & domain scores have a normative mean=100,with SD=15 & subdomain scores are normed with a mean=15 & SD=3.Higher scores indicate better,while lower scores indicate worse adaptive functioning.

  12. Anti-Idursulfase Antibodies (ADA) in Serum

    Time frame: From Baseline to End-of-Study (Approximately 9.75 years)

    Blood samples were collected and analyzed for determination of anti-idursulfase antibodies every 6 months in SHP-ELA-401. Analysis of anti-idursulfase antibodies including neutralizing antibodies (NAb) was conducted using validated 3-tier immunoassay methods (screening, confirmatory, and titer).

Sponsors and collaborators

Lead sponsor

Shire

Industry

Collaborators

  • Takeda Development Center Americas, Inc.

Registry information

Official study title

A Long-Term, Open-Label, Multicenter, Phase IV Study to Assess Longitudinal Changes on Height and Weight in Patients With MPS II Who Are Receiving Elaprase and Started Treatment With Elaprase at <6 Years of Age

Important dates

Study start
2015
Primary completion
2025
Study completion
2025
First posted
May 28, 2015
Registry last updated
Apr 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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