E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sanfilippo syndrome (Mucopolysaccharidosis III) |
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E.1.1.1 | Medical condition in easily understood language |
Mucopolysaccharidosis III is a disorder marked by severe neurological symptoms and is caused by deficiencies of specific lysosomal enzymes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056918 |
E.1.2 | Term | Sanfilippo's syndrome |
E.1.2 | System Organ Class | 100000004850 |
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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 objective of this trial is to evaluate oral genistein aglycone therapy in patients between 2 and 15 years old with MPS III A, B or C |
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E.2.2 | Secondary objectives of the trial |
Following 52 weeks of treatment are there changes in urinary GAG excretion; urine and plasma heparan sulphate; neuropsychological measures; actigraphy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Written informed consent of a legally authorised guardian(s); • Aged between 2 and 15 years of age (inclusive), at the time of informed consent; • The patient must be able to walk unaided; • The patient must have confirmed MPS III A ,B or C with: a fibroblast or leukocyte HeparanNsulphatase (HNS) or Nalphaacetylglucosaminidase (NAGLU) or HeparanalphaglucosaminideNAcetyltransferase (HGSNAT) activity level of less than 10% of the lower limit of the normal range, or below the detection range of the measuring laboratory or have HNS or NAGLU; AND/OR • HGSNAT mutations known to be pathogenic; •A clinical diagnosis of MPS III. |
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E.4 | Principal exclusion criteria |
• The patient has undergone bone marrow transplantation. • The patient is unable to participate in study activities in the opinion of the investigator. • The patient has a clinically significant organic disease (with the exception of symptoms relating to MPS III A or B or C) including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival. • Patients that have had a change in psychotropic medication within one month of randomisation. • The patient receives any investigational medicinal product within 90 days prior to trial enrolment. • Patients should not have received genistein in any form for 30 days prior to enrolling into the study. • The patient has known hypersensitivity or adverse reactions to genistein. • A positive pregnancy test in a patient of childbearing potential. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be CSF heparan sulphate at 52 weeks, adjusted for baseline, in patients allocated to drug compared with patients allocated to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
CSF samples will be collected at weeks 0, 52 and analysed. They will also be collected and analysed following the 52 week open label phase. |
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E.5.2 | Secondary end point(s) |
Urinary GAG excretion at 52 weeks. Urinary and plasma heparan sulphate at 52 weeks. Neuropsychological measures, including the Vineland adaptive behaviour Questionnaire; Connors questionnaire; Bayley scale III; and MPS III symptom checklist at 52 weeks. Actigraphy at 52 weeks. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These endpoints will be evaluated at 0 and 52 weeks, and following the 52 week open label phase |
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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 | 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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
There is a 52 week open label period following the double blind component |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | |
E.8.9.1 | In the Member State concerned days | |