Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
- Conditions
- PhenylketonuriaTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2015-001650-15-Outside-EU/EEA
- Lead Sponsor
- Merck Serono Middle East FZ-LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 90
•Willing and able to provide written informed consent (for children under 18 years old the parent[s]/guardians give informed consent, subjects 14-17 years old give additionally their own written informed consent)
•Age of 4 - 18 years, inclusive
•Confirmed clinical and biochemical hyperphenylalaninemia due to phenylketonuria documented by past medical history with at least 2 blood phenylalanine level greater than or equal to 400 micromole per liter obtained in 2 separate occasions
•Blood phenylalanine level at screening greater than or equal to 450 micromole per liter (mean of two measurements)
•For women of childbearing potential, a negative urine pregnancy test is required at screening and willingness to use a highly effective method of contraception is required while participating in the study
•Subject and/or the parent/guardian willing and able to comply with study procedures
•Subject and/or the parent/guardian willing to continue current diet unchanged during the 8 days response test and to adapt the diet according to phenylalanine therapeutic target range during the 6 week treatment period
Are the trial subjects under 18? yes
Number of subjects for this age range: 90
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
•Subject already assessed for responsiveness to sapropterin dihydrochloride or other tetrahydrobiopterin (BH4)
•Used any investigational agent other than Kuvan® (sapropterin dihydrochloride) within 30 days of screening, or required any investigational agent or vaccine prior to completion of all scheduled study assessments
•Pregnant or breastfeeding, or considering pregnancy
•Concurrent disease or conditions that would interfere with study participation or safety (for example, seizure disorder, asthma or other condition requiring oral or parenteral corticosteroid administration, insulin-dependent diabetes, or organ transplantation recipient)
•Concurrent use of required concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate), levodopa, phosphodiesterase type-5 (PDE-5) inhibitors (such as, sildenafil, vardenafil or tadalafil), medications that are known to affect nitric oxide synthesis metabolism or action
•Any conditions, that, in the view of the Principal Investigator renders the subject at high risk for failure to comply with treatment or to complete the study
•Clinical diagnosis of primary BH4 deficiency
•Known hypersensitivity to Kuvan® (sapropterin dihydrochloride) or its excipients or to other approved or non-approved formulation of tetrabiopterin
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: -To evaluate the frequency of response to Kuvan therapy after 8 days treatment with a daily dose of 20 mg/kg/day as assessed by a reduction in blood Phe level = 30 % among subjects with PKU aged 4-18 years who have elevated blood Phe levels (= 450 µmol/l).<br>-To evaluate the degree of response to Kuvan.<br>-To assess Kuvan safety in responsive patients with PKU after 6 weeks of treatment.;Secondary Objective: Not applicable;Primary end point(s): Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment ;Timepoint(s) of evaluation of this end point: Day 8
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population <br>Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders <br>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population ;Timepoint(s) of evaluation of this end point: Baseline, Day 8<br>Baseline, Day 8<br>Baseline up to Week 11