A Study of Elaprase in Children and Adults With Hunter Syndrome (Mucopolysaccharidosis II) in India

Study Overview
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Brief Summary
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The main aim of this study is to learn more about the safety profile of Elaprase in Indian children and adults with hunter syndrome. Participants will receive Elaprase once per week over a 3-hour period which can be reduced to 1 hour as determined by the study doctor. Participants will need to visit the clinic weekly during the duration of the study.

Official Title
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A Prospective, Multicenter, Single-arm, Open-label, Interventional Phase IV Study to Evaluate the Safety and Efficacy of Idursulfase (r-DNA Origin) (Elaprase™) in Indian Pediatric and Adult Population With Hunter Syndrome (Mucopolysaccharidosis II)

Conditions
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Hunter Syndrome

Intervention / Treatment
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* Biological: Elaprase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Elaprase naive participants (and who are not part of any other program at the time of study enrollment and during the study period) of any age with confirmed diagnosis of Hunter syndrome based on the following documented biochemical and genetic criteria: Documented deficiency in iduronate 2-sulfatase (IDS [12S]) enzyme activity of less than or equal to 10 percent (%) of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory). A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory). The participant has a documented mutation in the IDS gene. In the opinion of the investigator, the participant or the participant's parents/guardians are capable of understanding and complying with protocol requirements. The participant or, when applicable, the participant's parents/guardians/legal authorized representative (LAR) signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. If the participant participating in this study is greater than or equal to (>=) 7 years and less than (<) 18 years of age signs and dates an assent form. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (example, condom with or without spermicide) from signing of informed consent throughout the duration of the study. The female partner of a male participant should also be advised to use a highly effective/effective method of contraception. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective method of contraception from signing of informed consent throughout the duration of the study. Exclusion criteria: Participant has received hematopoietic stem cell transplant (HSCT) or a bone marrow transplant at any time. Participant is unable to comply with the protocol, example, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the investigator. Participant is suffering from any comorbid conditions (including hepatic impairment, acute or chronic) or having any other clinical observation or history during the screening examination, which would interfere with the objectives of the study as per investigators judgement. The participant has a chronic kidney disease with estimated Glomerular Filtration rate less than 15 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) and/or is on dialysis. The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (example, spouse, parent, child, sibling) or may consent under duress. The participant has a history of hypersensitivity or allergies to related compounds including any associated excipients. If female, the participant is pregnant or lactating or intending to become pregnant before participating in this study, during the study; or intending to donate ova during such time period. If male, the participant intends to donate sperm during the course of this study. The participant has participated in another clinical study or received any investigational compound or non-investigational idursulfase beta within the past 30 days before informed consent.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elaprase 0.5 mg/kg<br>Participants will receive a single dose of Elaprase 0.5 milligrams per kilogram (mg/kg) body weight, intravenous infusion on Day 1, Week 1 followed by every week up to end of treatment (EOT) (Day 358, Week 52). | Biological: Elaprase<br>* Participants will receive a single dose of Elaprase 0.5 mg/kg intravenous infusion every week on Day 1.<br>* Other names: Idursulfase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in: death; is life-threatening: requires inpatient hospitalization or results in prolongation of existing hospitalization; persistent or significant disability/incapacity; leads to a congenital anomaly/birth defect or is an important medical event. AEs include SAEs, treatment emergent AEs, treatment emergent SAEs, discontinuation due to AEs, and death. | From start of the study drug administration up to end of study (EOS) (Week 53) | 
| Number of Participants With Adverse Drug Reactions (ADRs) | An ADR is defined as a response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. | From start of the study drug administration up to EOS (Week 53) | 
| Number of Participants With Infusion-related Reactions (IRRs)) | An IRR is defined as an AE that has been assessed as at least possibly related to treatment with Elaprase and occurs during an infusion or up to 24 hours post-infusion. | From start of the study drug administration up to EOS (Week 53) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percentage Forced Vital Capacity (%FVC) at Week 27 and 53 | FVC is the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible, as measured by spirometry. FVC is a measure of respiratory function. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in 6 Minute Walk Test (6MWT) at Week 27 and 53 | 6MWT is a measure of physical functional capacity which is determined on a walking course. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in Cardiac Left Ventricular Mass Index (LVMI) at Week 27 and 53 | Cardiac LVMI will be measured by 2-dimensional (2D) echocardiography. Cardiac LVMI is the left ventricular mass (LVM, in grams [g]) indexed to body surface area (BSA), in square meter (m^2). Cardiac LVMI (in gram per square meter [g/m^2])=LVM divided by BSA. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in Ejection Fraction at Week 27 and 53 | The Ejection Fraction is measured by 2D echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in Liver Volume at Week 27 and 53 | Liver volume will be determined by Ultrasonography (USG). Hepatomegaly is defined as a liver volume (Liter [L]) greater than (>) 3.5% of body weight (kilogram [kg]) in participants aged 5-12 years, 2.2% of body weight in participants aged 13-17 years, and >2.6% in participants more than 18 years old (30). | Baseline, Weeks 27 and 53 | 
| Change From Baseline in Spleen Volume at Week 27 and 53 | Spleen volume will be determined by USG. Splenomegaly is defined as having a splenic volume greater than the 95th percentile of the normal distribution in children. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in Normalized Urine Glycosaminoglycan (uGAG) Levels at Week 14, 27, 40, and 53 | Normalized uGAG will be analyzed using urine testing. The uGAG levels will be normalized to urine creatinine and will be reported as microgram GAG per milligram creatinine (mcg GAG/mg creatinine). | Baseline, Weeks 14, 27, 40, and 53 | 
| Change From Baseline in Global Joint Range of Motion (JROM) Score at Week 27 and 53 | Passive joint mobility is defined as the range of motion of the shoulder, elbow, wrist, hip, knee, and ankle joints, as assessed by one expert physician using universal goniometry method. Global JROM (% of normal range of motion) is the average of 11 ratios multiplied by 100. Ratios are left/right means of passive range of motion in shoulder (flexion/extension, abduction, internal/external rotation), elbow (flexion/extension), wrist (flexion/extension), index finger (flexion/extension [combined metacarpophalangeal joint, proximal interphalangeal joint, distal interphalangeal joint motion]), hip (flexion/extension, abduction, internal/external rotation), knee (flexion/extension), and ankle (dorsiflexion) divided by the normal range (American Academy of Orthopedic Surgeons and American Medical Association). It ranges from 0-100 where, 0- No movement and 100- Normal. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in Anthropometric Parameter (Height) | Change from baseline in height (centimeters) will be assessed in participants less than (<) 18 years at Weeks 27 and 53. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in Anthropometric Parameter (Weight) at Weeks 27 and 53 | Change from baseline in weight (kilograms) will be assessed in all participants at Weeks 27 and 53. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in the Health-related Quality of Life (HRQoL) Based on Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) | HS-FOCUS was developed as disease-specific measure of the impact of Hunter syndrome on HRQL. The HS-FOCUS is designed to gather information on the participant's daily life and wellbeing, satisfaction with treatment, and hospitalizations, as well as on how Hunter syndrome impacts participant's general quality of life. HS-FOCUS includes 2 validated components: a parent version and a participant self-reported version for those over age 12 years. The HS-FOCUS (shortened version) questionnaire has 5 function domains (walking/standing, grip/reach, school/work, activities, and breathing). Items are scored using a response scale from 0 to 3, with 0 signifying an ability to complete the activity-related functions 'without any difficulty' and 3 score denoting highest disability. | Baseline, Weeks 27 and 53 | 
| Change From Baseline in the HRQoL Based on Childhood Health Assessment Questionnaire (CHAQ) | The CHAQ was initially developed for assessing juvenile idiopathic arthritis, from the perspective of the parent or participant, and has been previously applied to other chronic disabling conditions such as Hunter syndrome. It is a 30-item instrument that measures functional capacity and independence in activities of daily life across eight domains: dressing and grooming, arising, eating, walking, reach, grip, hygiene, and activities. For each domain, there is a 4-level difficulty scale that is scored from 0 to 3, with 0 corresponding to 'without any difficulty' and 3 to 'unable to do'. | Baseline, Weeks 27 and 53 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mucopolysaccharidosis II