E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mucopolysaccharidosis Type IVA |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028095 |
E.1.2 | Term | Mucopolysaccharidosis IV |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 |
• To evaluate the safety of 2.0 and 4.0 mg/kg/week BMN 110 administered for 27 weeks
The primary objective for extending the Phase 2 study is:
• To evaluate the long-term safety of 2.0 and 4.0 mg/kg/week BMN 110 in patients with MPS IVA |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of 2.0 and 4.0 mg/kg/week BMN 110 administered for 24 weeks to enhance endurance
• To evaluate the effect of 2.0 and 4.0 mg/kg/week BMN 110 administered for 25 weeks on overall exercise capacity (VO2 max)
• To evaluate the effect of 2.0 and 4.0 mg/kg/week BMN 110 administered for 24 weeks on respiratory function tests (RFTs)
• To evaluate the effect of 2.0 and 4.0 mg/kg/week BMN 110 administered for 25 weeks on muscle strength
• To evaluate the effect of 2.0 and 4.0 mg/kg/week BMN 110 administered for 24 weeks on cardiac function
• To evaluate the effect of 2.0 and 4.0 mg/kg/week BMN 110 administered for 24 weeks on pain
• To evaluate the effect of 2.0 and 4.0 mg/kg/week BMN 110 administered for 24 weeks on plasma and urinary KS levels
• To determine the pharmacokinetic (PK) parameters of 2.0 mg/kg/week and 4.0 mg/kg/week BMN 110
The secondary objectives of the extension phase of the study are described on pages 8-9 of the revised protocol. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Has documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA
• Is at least 7 years of age
• Is able to walk ≥ 200 meters as assessed by the 6MWT
• If sexually active, is willing to use an acceptable method of contraception while participating in the study
• If female of childbearing potential, must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study
(Refer to the Study Protocol for a complete list of inclusion criteria) |
|
E.4 | Principal exclusion criteria |
• Inability to perform an exercise test due to limited mobility
• Body weight greater than 95 kg at screening
• Severe, untreated sleep apnea as measured during screening with a home sleep testing device
• Requirement for supplemental oxygen
• Use of ventilator assistance in the 3 months prior to study entry
• Has a concurrent disease or condition, including but not limited to, symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation, or pose a safety risk, as determined by the Investigator.
• Has previous hematopoietic stem cell transplant
• Has received previous treatment with BMN 110
• Has a known hypersensitivity to BMN 110 or its excipients
• Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the duration of the study
• Is pregnant or breastfeeding during the Screening Period or planning to become pregnant (self or partner) at any time during the study
(Refer to the Study Protocol for a complete list of exclusion criteria) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety:
Primary Variables:
Primary safety variables will be assessed using:
• AEs, including serious AEs (SAEs)
• Vital signs
• ECGs
• Physical examinations (including neurologic examination)
• Standard clinical laboratory tests (serum chemistry, hematology, and urinalysis)
• Concomitant medications
• Immunogenicity tests |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed at Screening and each visit |
|
E.5.2 | Secondary end point(s) |
Efficacy:
Secondary Variables:
Secondary efficacy variables will be assessed using:
• 6MWT
• 3MSC test
• CPET
• RFT
• MST
• Pain
• ECHO
• Overnight monitoring with home sleep testing device
• Plasma KS
• Urine KS concentration normalized to creatinine
• PK parameters |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Evaluate the effect of BMN 110 to enhance endurance: Assessed at Screening, Wks 12, 24, 52 and every 52 wks
• Evaluate the effect on overall exercise capacity (VO2 max): at Screening, wks 25, 52 and every 52 wks
• Evaluate the effect on respiratory function tests (RFTs): at Screening, wks 12, 24, 52 and every 52 wks
• Evaluate the effect on muscle strength: at Screening, wks 25, 52 and every 52 wks
• Evaluate the effect on cardiac function: at Screening, wks 24, 52 and every 52 wks
• Evaluate the effect on pain: at Screening, wks 12, 24, 52 and every 52 wks
• Evaluate the effect on plasma and urinary KS levels: at Screening, wks 1, 2, 4, 6, 12, 24, 52 and every 26 wks
• Determine the pharmacokinetic (PK) parameters of BMN 110 Assessed at Weeks 0 and 23 |
|
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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
Canada |
Germany |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
End of trial is defined as 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 | 3 |
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 | 3 |
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 |