Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU

NCT00838435 | Completed Phase 3 Results

• 1 other identifier: PKU-015
• Study Type: interventional
• Target: 95
• Locations: 2 countries
• Sites: 19

Brief Summary

This multicenter, open label study is designed to evaluate the safety of Kuvan® and its effect on neurocognitive function, blood Phe concentration, and growth in children with PKU who are 0-6 years old.

Conditions

Phenylketonuria

Keywords

Phenylketonuria; PKU; Kuvan; Phenoptin; Biopten; Neurocognitive Function; Phenylalanine

Outcome Measures

Primary Outcomes (1)

• Full-Scale Intelligence Quotient (FSIQ) Score

  Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children \>30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children \>6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests. FSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient.

  Assessments through 84 months.

Secondary Outcomes (9)

• Number of Subjects With Adverse Events (AEs)

  Up to 7 years

• Change From Baseline in Growth Measurements - Height Z-Scores

  Baseline and up to 84 months

• Change From Baseline in Growth Measurements - Weight Z-Scores

  Baseline and up to 84 months

• Change From Baseline in Growth Measurements - Head Circumference Z-Scores

  Baseline and up to 84 months

• Change From Baseline in Bayley-III Scores - Neurocognitive Testing Results

  At Month 6, 12, 18 and 24

Study Arms (1)

sapropterin dihydrochloride

EXPERIMENTAL

A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food.

Drug: sapropterin dihydrochloride

Interventions

sapropterin dihydrochloride DRUG

A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food.

Also known as: Kuvan, Phenoptin, BH4, 6R BH4

sapropterin dihydrochloride

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Established diagnosis of PKU with hyperphenylalaninemia (HPA) documented in the medical record by at least 2 blood Phe concentrations greater than or equal to 360 micromole/L (6 mg/dL) taken at least 3 days apart
• Documented blood Phe control (defined by the standard used at each treatment center) prior to study enrollment, if applicable (eg, the subject is old enough for these data to be collected); blood Phe concentrations for subjects \< 6 months old at Screening must be considered controlled and stable by the Investigator
• Willing to adhere to a prescribed Phe restricted diet in order to maintain blood Phe concentrations within the recommended ranges established at the subject's study site
• Age 0 to 6 years old, inclusive, at Screening
• Parent(s) or guardian(s) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Parent(s) or guardian(s) willing and able to comply with all study procedures
• Female subjects of childbearing potential (as determined by the investigator) and sexually mature male subjects willing to use a medically accepted method of contraception throughout the study. Female subjects of childbearing potential willing to undergo periodic pregnancy tests during the course of the study

You may not qualify if:

• Established diagnosis of primary tetrahydrobiopterin (BH4) deficiency
• Known hypersensitivity to Kuvan or its excipients
• History of organ transplantation
• Perceived to be unreliable or unavailable for study participation or to have parents or legal guardians who are perceived to be unreliable or unavailable
• Use of methotrexate or other medications that inhibit folate metabolism
• Serious neuropsychiatric illness (eg, major depression) not currently under medical control
• Use of Kuvan or any investigational agent within 30 days prior to Screening, or known requirement for any investigational agent prior to completion of all scheduled study assessments
• Concurrent disease or condition that would interfere with study participation or safety (eg, seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, or insulin dependent diabetes)
• Any condition that, in the view of the Principal Investigator (PI), renders the subject at high risk for failure to comply with treatment or to complete the study
• Use of phosphodiesterase type 5 (PDE5) inhibitor.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (19)

Unknown Facility

La Jolla, California, United States

Location

Unknown Facility

Orange, California, United States

Location

Unknown Facility

Tampa, Florida, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

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Boston, Massachusetts, United States

Location

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Kansas City, Missouri, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Hershey, Pennsylvania, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

Milwaukee, Wisconsin, United States

Location

Unknown Facility

Edmonton, Alberta, Canada

Location

Unknown Facility

Vancouver, British Columbia, Canada

Location

Unknown Facility

Winnipeg, Manitoba, Canada

Location

Unknown Facility

Hamilton, Ontario, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Unknown Facility

Sainte-Foy, Quebec, Canada

Location

MeSH Terms

Conditions

Phenylketonurias

Interventions

sapropterin; phenoptin

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Joshua Lilienstein/Medical Director, Global Medical Affairs
• Organization: BioMarin Pharmaceutical Inc.

MEDINFO@bmrn.com

651.523.0310

Study Officials

• Joshua Lilienstein, M.D.

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2009
• First Posted: February 6, 2009
• Study Start: February 1, 2009
• Primary Completion: September 14, 2018
• Study Completion: September 14, 2018
• Last Updated: December 22, 2020
• Results First Posted: December 22, 2020

Record last verified: 2020-12

Locations

US (12); CA (7)