A multicentre, open-label study to evaluate the efficacy and safety of 5-MTHF administration, added on to the individual established therapy, on plasma homocysteine levels in patients with congenital homocystinuria

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-000614-21-GB
• Date of registration: 20/09/2006
• Prospective Registration: Yes
• Primary sponsor: Zambon Group S.p.A
• Public title: A multicentre, open-label study to evaluate the efficacy and safety of 5-MTHF administration, added on to the individual established therapy, on plasma homocysteine levels in patients with congenital homocystinuria
• Scientific title: A multicentre, open-label study to evaluate the efficacy and safety of 5-MTHF administration, added on to the individual established therapy, on plasma homocysteine levels in patients with congenital homocystinuria
• Date of first enrolment: 13/10/2006
• Target sample size: 22
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000614-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Hungary, Italy, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. signed informed consent (patient or Legal responsible)
2. >16 years of age
3. classical (non-pyridoxine responsive) homocystinuria (CBS deficiency)
4. stable clinical condition
5. willing to complete all phases and all procedures of the study
6. on B6, B12, betaine and folic acid treatment
7. ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study; signed written informed consent prior to inclusion in the study

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

Exclusion criteria:
1. patients taking multivitamin supplements, folic acid or creatine treatment at inclusion and throughout the duration of the study
2. episodes of thrombosis and/or embolism one year before inclusion in the study
3. history of drug and/or alcohol abuse during the 6 months before the beginning of the study
4. patients with serious illness(es) or diseases (e.g., haematological, renal, hepatic, respiratory, endocrine, psychiatric) that may interfere with, or put patients at additional risk for their ability to receive the treatment outlined in the protocol
5. donation or receipt of blood or blood products (within 2 months before baseline)
6. pregnant or lactating female



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

Health Condition(s) or Problem(s) studied

homocystinuria
MedDRA version: 8.1 Level: pref Classification code 10020365

Intervention(s)

Trade Name: Prefolic
Pharmaceutical Form: Tablet
INN or Proposed INN: 5-MTHF
CAS Number: 134-35-0
Other descriptive name: IUPAC name: 2-[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylam ino]benzoyl]amino
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Secondary Objective: Change from baseline values of plasma tHcy after 2 weeks and 1 month of treatment
Change of tHcy plasma values from screening (folic acid treatment) to baseline and after 3 months of treatment
Change from baseline values of: urine homocystine, S-adenosylhomocysteine, S-adenosyl methionine, methionine, endothelial dysfunction factors as the tissue-type plasminogen activated antigen (t-PA) and Plasminogen activator inhibitor type-1 antigen (PAI-1) in plasmaafter 2 weeks, 1 and 3 months of treatment
Change from baseline of the isoprostane 8-iso-PGF2a concentrations in urine as a marker of the enhanced peroxidation of arachidonic acid and platelet activation after 2 weeks, 1 and 3 months of treatment.
Change from baseline of fibrinogen levels, partial prothrombine time (PTT), prothrombine time (PT) and coagulation factor V Leiden in plasma after 2 weeks, 1 month and 3 months of treatment.

Main Objective: To investigate the efficacy and safety of a 3 month 5-MTHF treatment in terms of decreasing total plasma Hcy (tHcy) in homocystinuric patients, while co-administered with an individual established therapy as a folic acid substitute.

Primary end point(s): To determine:
Reduction from baseline of total Hcy (tHcy) in plasma after a 3 month treatment with 5-MTHF 15 mg. Baseline will be defined as the values obtained after the wash-out phase before 5-MTHF first intake.

Secondary ID(s)

2006-000614-21-AT

7168K01