Clinical trial NCT01016392: Observational Study on the Long Term Safety of Kuvan® Treatment in Patients With Hyperphenylalaninemia (HPA) Due to Phenylketonuria (PKU) or BH4 Deficiency
Official title: Kuvan® Adult Maternal Pediatric European Registry
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hyperphenylalaninemia (HPA) Due to Phenylketonuria (PKU) or Tetrahydrobiopterin (BH4) Deficiency
Keywords: Observational post-authorization safety study on Kuvan®.
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2009-11-19
Enrollment: 627
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All subjects with HPA due to PKU or BH4 deficiency followed at participating centres.

And specific groups (elderly, pediatric, pregnant women and subjects with renal or hepatic insufficiency).

Brief summary: Kuvan® is a synthetic copy of a body's own substance called tetrahydrobiopterin (BH4). BH4 is required by the body to use an amino acid called phenylalanine in order to build another substance called tyrosine.

Kuvan® received marketed authorisation in Europe in December 2008 and is now available in several European countries for the treatment of Hyperphenylalaninemia (HPA).

The primary objective is to assess the long-term safety in subjects treated with Kuvan®.

Secondary objectives are to provide additional information regarding:

* Safety in specific subject groups (elderly, pediatric, pregnant women and subjects with renal or hepatic insufficiency).
* Growth and neurocognitive outcomes for subjects with hyperphenylalaninemia (HPA) who are receiving treatment with Kuvan®.
* Progress and outcome of pregnancy for women with HPA who become pregnant while receiving treatment with Kuvan® (these women will be enrolled in a dedicated sub-registry).
* Assessment of adherence to diet and to Kuvan®.
* Assessment of long-term sensitivity to Kuvan®treatment.

Detailed description: This is an observational, multicenter, drug registry Study. The study will have a total duration of 15 years, including a 10-year inclusion period. No diagnostic, therapeutic or experimental intervention is involved. Subjects will receive clinical assessments, medications and treatments solely as determined by their study physician.

Eligibility criteria: Inclusion Criteria:

* Adult or pediatric subject (no age limit) of either gender with HPA due to PKU or BH4 deficiency.
* Have been shown to be responsive to BH4 or Kuvan. (Note: For Spain only-Have been shown to be responsive to BH4 or for the newly diagnosed subjects to be responsive to Kuvan as defined in the Summary of Product Characteristics \[SmPC\]).
* Currently being treated with Kuvan® at a participating centre.
* Subject or parent/legal guardian willing and able to provide written signed informed consent and given before any data collection. If a child is old enough to read and write, a separate assent form will be given.

Exclusion Criteria:

* Known hypersensitivity to Kuvan®
* Legal incapacity or limited legal capacity without legal guardian representation
* Breast-feeding

Primary outcomes:
measure: Incidence and description of Adverse Events and Serious Adverse Events (AEs/SAEs)
timeFrame: A maximum of 15 years treatment duration.
Secondary outcomes:
measure: Incidence of AEs/SAEs in specific population (elderly, children, subjects with renal or hepatic insufficiency)
timeFrame: A maximum of 15 years treatment duration.
measure: Description on somatic growth (in BH4 deficient children < 3 years)
timeFrame: A maximum of 15 years treatment duration.
measure: Neurocognitive outcomes
timeFrame: A maximum of 15 years treatment duration.
measure: Neurological and psychiatric assessment
timeFrame: A maximum of 15 years treatment duration.
measure: Diet and Kuvan® treatment adherence
timeFrame: A maximum of 15 years treatment duration.
measure: Long-term sensitivity to Kuvan® treatment
timeFrame: A maximum of 15 years treatment duration.
measure: Blood Phe levels
timeFrame: A maximum of 15 years treatment duration.
measure: Tyrosine (Tyr) levels
timeFrame: A maximum of 15 years treatment duration.
measure: Pregnancy and delivery outcomes
timeFrame: A maximum of 15 years treatment duration.
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Vienna
country: Austria
facility: Research Site
city: Amiens
country: France
facility: Research Site
city: Angers
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Bron
country: France
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Limoges
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site - Armand Trousseau
city: Paris
country: France
facility: Research Site - Necker
city: Reims
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Tarbes
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Tours
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Cottbus
country: Germany
facility: Research Site
city: Duesseldorf
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Muenchen
country: Germany
facility: Research Site
city: Muenster
country: Germany
facility: Research Site
city: Reutlingen
country: Germany
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Catanzaro
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site - Ospedale Annunziata
city: Napoli
country: Italy
facility: Research Site - Policlinico Federico
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Banska Bystrica
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Bilbao
country: Spain
facility: Research Site
city: Esplugues De Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Murcia
country: Spain
facility: Research Site
city: Palma De Mallorca
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Santa Cruz de Tenerife
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Gothenburg
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
Study officials:
affiliation: BioMarin Pharmaceutical
name: Ece Kucuksayrac, MD
role: STUDY_DIRECTOR
References: