Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response

The investigators will investigate the effect of blood phenylalanine on Kuvan responsiveness in the same patients with PKU when their blood phenylalanine concentrations are altered by diet.

Lowering blood phenylalanine concentrations in Kuvan non-responsive patients with PKU will increase the frequency of Kuvan responsiveness.

Study Overview

• Status: Completed
• Conditions: Phenylketonuria
• Intervention / Treatment: Drug: Kuvan; Other: Diet

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Department of Biochemistry & Molecular Biology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• all patients with a diagnosis of phenylketonuria
• patients who are over the age of 4 years,
• patients with a fasting blood phenylalanine ≥600µmol/l

Exclusion Criteria:

• female patients who are pregnant or attempting to become pregnant
• children under four years of age
• Concurrent disease of condition that would interfere with study participation or safety such as history of neurological compromise or major medical, psychiatric or learning disorder unrelated to PKU
• Any condition that, in the view of the Investigators, places subject at high risk of poor treatment compliance or of not completing the study
• Use of L-Dopa, methotrexate, or other drugs that may inhibit folate metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acute 24 Hour Component; Participants will receive one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response.	Drug: Kuvan; 20mg/kg by mouth once daily; Other Names: sapropterin dihydrochloride, Tetrahydrobiopterin (BH4)
EXPERIMENTAL: Phase 1 Group; After completion of acute 24 hour component, participants can enroll in Phase 1 and will receive Kuvan 20 mg/kg by mouth once daily for 28 consecutive days	Drug: Kuvan; 20mg/kg by mouth once daily; Other Names: sapropterin dihydrochloride, Tetrahydrobiopterin (BH4)
EXPERIMENTAL: Phase 2 Group; Participants in Phase 1 that was not responsive will continue on to the Phase 2 of the study. Positive response is defined as a decrease of blood phenylalanine of 30% or greater from baseline taken from morning blood serum. The Phase 2 component of the study will be a 2 week period of dietary restriction.	Other: Diet; Phenylalanine-restricted diet (4-10 mg/kg/day phenylalanine) using the prescribed phenylalanine-free medical formula and low protein foods tested with the patients for taste and acceptance to lower blood phenylalanine levels below 600 umol/l.
EXPERIMENTAL: Phase 3 Group; Participants in Phase 2 that achieves a fasting blood phenylalanine of less than 600 umol/l after 2 week dietary restriction will be retreated with Kuvan 20 mg/kg by mouth once daily for a period of 28 consecutive days.	Drug: Kuvan; 20mg/kg by mouth once daily; Other Names: sapropterin dihydrochloride, Tetrahydrobiopterin (BH4)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Blood Phenylalanine	Percent change in phenylalanine in (uM) on Kuvan Response evaluated via fasting morning blood serum. A decrease of 30% or greater indicates positive response on Kuvan.	Baseline to Day 1 of the Acute Phase, Baseline to Day 28 of Phase 1, Baseline to Day 28 of Phase 3

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Louis J Elsas, MD, University of Miami

Publications and helpful links

General Publications

• Burton BK, Grange DK, Milanowski A, Vockley G, Feillet F, Crombez EA, Abadie V, Harding CO, Cederbaum S, Dobbelaere D, Smith A, Dorenbaum A. The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study. J Inherit Metab Dis. 2007 Oct;30(5):700-7. doi: 10.1007/s10545-007-0605-z. Epub 2007 Sep 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2008
• Primary Completion (ACTUAL): July 19, 2011
• Study Completion (ACTUAL): July 19, 2011

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 10, 2009
• First Posted (ESTIMATE): February 11, 2009

Study Record Updates

• Last Update Posted (ACTUAL): December 3, 2019
• Last Update Submitted That Met QC Criteria: November 19, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: tetrahydrobiopterin; PKU; Kuvan; BH4
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: 20080675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No