Metabolic Disorders - Phenylketonuria MedDRA version: 20.0 Level: LLT Classification code 10034873 Term: Phenylketonuria (PKU) System Organ Class: 100000004850
Conditions
Sponsors
PTC Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent and assent (if necessary, at the investigator’s discretion [ie, for children) with parental/legal guardian consent 2. Male or female subjects of any age 3. Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by past medical history of at least 2 blood Phe measurements =600 µmol/L 4. Women of childbearing potential, as defined in (CTFG 2020), must have a negative pregnancy test at study entry and agree to abstinence or the use of at least one highly effective form of contraception (with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. The individual, in the opinion of the investigator, is unwilling or unable to adhere to the requirements of the study 2. Inability to tolerate oral medication 3. A female who is pregnant or breastfeeding, or considering pregnancy 4. Serious neuropsychiatric illness (eg, major depression) not currently under medical control, that in the opinion of the investigator or sponsor, would interfere with the subject’s ability to participate in the study or increase the risk of participation for that subject 5. Past medical history and/or evidence of renal impairment and/or condition including moderate/severe renal insufficiency (glomerular filtration rate [GFR] <60 mL/min) as estimated most recently during qualifying participation in a feeder study) and/or under care of a nephrologist 6. Any other condition that in the opinion of the investigator or sponsor, would interfere with the subject’s ability to participate in the study or increase the risk of participation for that subject 7. Requirement for concomitant treatment with any drug known to inhibit folate synthesis (eg, methotrexate) 8. Concomitant treatment with BH4 supplementation (eg, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ) Additional criteria for subjects who did not participate in a feeder study: 9. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, and peptic ulcer disease, etc) that could affect the absorption of study drug 10. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy 11. History of allergies or adverse reactions to synthetic BH4 or sepiapterin 12. Current participation in any other investigational drug study or use of any investigational agent within 30 days prior to Screening 13. Any clinically significant laboratory abnormality as determined by the investigator. In general, each laboratory value from Screening and baseline chemistry and hematology panels should fall within the limits of the normal laboratory reference range, unless deemed not clinically significant by the investigator 14. Any abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated GFR <60 mL/min/1.73 m2. In subjects =18 years of age, the Modification of Diet in Renal Disease Equation should be used to determine GFR. In subjects <18 years of age, the Bedside Schwartz Equation should be used to determine GFR. 15. Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive GTP cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin 4-alpha-carbinolamine dehydratase genes 16. Major surgery within the prior 90 days of screening 17. Unwillingness to washout from BH4 supplementation (eg, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the long-term safety of PTC923 in subjects with PKU • To evaluate changes from baseline in dietary Phe/protein consumption;Secondary Objective: • To evaluate PTC923 effect on quality of life (QOL) using the Phenylketonuria-quality of life (PKU-QOL) questionnaire in the subset of subjects who are able to complete the PKU-QOL (ie, subjects whose primary language is English [British or American], Turkish, Dutch, German, Spanish, Italian, Portuguese, or French) (ages 6 to 8 years Parent PKU-QOL; ages 9 to 11 years Child PKU-QOL; ages 12 to 17 years Adolescent PKU-QOL; ages =18 years Adult PKU-QOL) • To evaluate PTC923 effect of QOL using the European Quality of Life 5 Dimensions (EQ-5D) (EQ-5D for Youth [EQ-5D-Y] Proxy Version 1 [3 to 7 years]; EQ-5D-Y [8 to 15 years]; EQ-5D– 5 Levels (EQ-5D5L ([=16 years]) •To evaluate the pharmacokinetics (PK) of sepiapterin and tetrahydrobiopterin (BH4) following PTC923 dosing ;Primary end point(s): Safety is a primary endpoint: Safety of long-term treatment with PTC923 will be measured by number of treatment-emergent adverse events (TEAEs), including assessment of severity of TEAEs, clinical laboratory tests, vital signs, and physical examinations. The primary efficacy endpoint is the change from baseline in dietary Phe/protein consumption measured during Dietary Phe Tolerance Assessment period.;Timepoint(s) of evaluation of this end point: Safety of long-term treatment with PTC923 will be measured by number of treatment-emergent adverse events (TEAEs), including assessment of severity of TEAEs, clinical laboratory tests, vital signs, and physical examinations. Dietary Phe tolerance evaluated at Baseline and every 2 weeks over the course of 26 week assessment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Changes from baseline in QOL using PKU-QOL questionnaire in the subset of subjects who are able to complete the PKU-QOL (ie, subjects whose primary language is English [British or American], Turkish, Dutch, German, Spanish, Italian, Portuguese, or French) (ages 6 to 8 years Parent PKU-QOL; ages 9 to 11 years Child PKU-QOL; ages 12 to 17 years Adolescent PKU-QOL; ages =18 years Adult PKU-QOL) • Changes from baseline in QOL using the EQ-5D (EQ-5D-Y Proxy Version 1 [3 to 7 years]; EQ-5D-Y [8 to 15 years]; EQ-5D-5L ([=16 years]) • PK assessment of sepiapterin and BH4 concentrations in plasma following dosing of sepiapterin ;Timepoint(s) of evaluation of this end point: Secondary measures will be evaluated at 6-month intervals starting at M8D1. | — |
Countries
Australia, Brazil, Canada, Denmark, France, Georgia, Germany, Italy, Mexico, Netherlands, Portugal, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactPatient Advocacy
PTC Therapeutics Inc.
Outcome results
None listed