E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hunter syndrome (Mucopolysaccharidosis II, [MPS II]) |
|
E.1.1.1 | Medical condition in easily understood language |
Hunter syndrome, is a rare, inherited disease caused by a deficiency in an enzyme called iduronate-2-sulfatase. This causes glycosaminoglycans (GAGs) to build up in the body and cause damage. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of this study are to assess longitudinal changes in the following
parameters in patients with MPS II who began Elaprase treatment at <6 years of age and who are receiving treatment with Elaprase:
• height
• weight |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to assess longitudinal changes in the following
parameters in patients with MPS II who began Elaprase treatment at <6 years of age and who are receiving treatment with Elaprase:
• urinary GAG levels
• liver and spleen volume
• joint mobility, as measured by Joint Range of Motion (JROM) scores, including global,
upper-limb, and lower-limb joint scores
• distance walked, as measured by the 6 Minute Walk Test (6MWT)
• quality of life, as measured by the Hunter-syndrome Functional Outcome in Clinical
Understanding Scale (HS-FOCUS) questionnaire (shortened version)
• impact of illness on ability to function in daily life, as measured by the Childhood Health
Assessment Questionnaire (CHAQ)
• adaptive behavior as measured by the Vineland Adaptive Behavior Scales (VABS-II) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet ALL of the inclusion criteria for his group in order to enroll in the trial.
1. The patient is male.
2. The patient is Elaprase-naïve at study entry.
3. 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:
a. 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
b. The patient has a documented mutation in the I2S gene.
OR
c. 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).
4. The patient will be <6 years of age at the start of Elaprase treatment.
5. 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 |
|
E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria are not eligible for enrollment into this study.
1. The patient has received treatment with any investigational drug or device within the 30 days prior to study entry.
2. The patient has received or is receiving treatment with idursulfase-IT.
3. The patient has received growth hormones, a cord blood infusion, or a bone marrow
transplant at any time.
4. The patient has received blood product transfusions within 90 days prior to Screening.
5. The patient is unable to comply with the protocol as determined by the Investigator.
6. The patient has a history of severe or life-threatening hypersensitivity to the active substance or to any of the excipients if hypersensitivity is not controllable. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Following are the primary variables to be assessed in this study:
• Height and weight
• Height and weight Z-scores
• Safety assessments
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Data will be collected from the baseline visit and throughout the study and evaluated following the End-of-study visit. |
|
E.5.2 | Secondary end point(s) |
Changes in the following additional variables will be assessed in this study:
• Urinary GAG (uGAG) levels normalized to urine creatinine
• Normalized uGAG divided by upper limit of normal for age (uGAG/ULN)
• Joint mobility, as measured by JROM scores, including global, upper-limb, and lower-limb joint scores
• Distance walked, as measured by the 6MWT
• Quality of life, as measured by the HS-FOCUS (shortened version), including individual
domain scores from the 5 functional domains: walking/standing, grip/reach, schooling/work, activities, and breathing
• Impact of illness on ability to function in daily life, as measured by the CHAQ Parent Report, including the Disability Index (based on 8 subscales: dressing, hygiene, arising, eating, walking, reach, grip and activities), Discomfort Index and Health Status index
• Adaptive behavior, as measured by the VABS- II: standardized scores for each of
4 domains: Communication; Daily Living Skills; Socialization; Motor Skills; as well as the
Adaptive Behavior Composite (ABC) score
• Antibody status
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Data will be collected from the baseline visit and throughout the study and evaluated following the End-of-study visit. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
This study is designed to evaluate growth in patients with MPS II who initiate treatment with Elaprase at <6 years of age. |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Costa Rica |
Dominican Republic |
Malaysia |
Oman |
Philippines |
Saudi Arabia |
Serbia |
Thailand |
United States |
Viet Nam |
Germany |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |