High Dose Genistein in Sanfilippo Syndrome

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2013-001479-18-GB
• Date of registration: 01/05/2014
• Prospective Registration: Yes
• Primary sponsor: Manchester University NHS Foundation Trust
• Public title: High Dose Genistein in Sanfilippo Syndrome
• Scientific title: A Phase III, Double Blinded, Randomised, Placebo Controlled Clinical Trial of High Dose Oral Genistein Aglycone in Patients with Sanfilippo Syndrome (Mucopolysaccharidosis III) - High Dose Genistein in Sanfilippo Syndrome
• Date of first enrolment: 09/06/2014
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001479-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: There is a 52 week open label period following the double blind component If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Lynne Webster
• Affiliation: Manchester University NHS Foundation Trust

• Name: Lynne Webster
• Affiliation: Manchester University NHS Foundation Trust

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Sanfilippo syndrome (Mucopolysaccharidosis III)
MedDRA version: 20.0 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 100000004850

Intervention(s)

Product Name: Genistein aglycone
Product Code: 500 0500 0
Pharmaceutical Form: Oral powder
INN or Proposed INN: Genistein aglycone
CAS Number: 446-72-0
Other descriptive name: GENISTEIN
Concentration unit: % percent
Concentration type: not less then
Concentration number: 98-

Primary Outcome(s)

Main Objective: 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

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.

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.

Secondary Objective: Following 52 weeks of treatment are there changes in urinary GAG excretion; urine and plasma heparan sulphate; neuropsychological measures; actigraphy.

Secondary Outcome(s)

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.

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

Secondary ID(s)

GENiSIS2013

Source(s) of Monetary Support

DSM Nutritionals

Society for Mucopolysaccharide Diseases

Ethics review

Status: Approved
Approval date:
Contact: