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 and/or subjects who are mentally impaired secondary to disease]) with parental/legal guardian consent 2.Male or female subjects of any age 3.Uncontrolled blood Phe level =360 µmol/L on current therapy anytime during Screening and uncontrolled blood Phe level =360 µmol/L on current therapy when taking the average of the 3 most recent Phe levels from the subject's medical history (inclusive of the Screening value). 4.Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by past medical history of at least 2 blood Phe measurements =600 µmol/L 5.Women of childbearing potential, as defined in (CTFG 2020), must have a negative pregnancy test at Screening 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.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 3.History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy 4.Inability to tolerate oral medication 5.History of allergies or adverse reactions to synthetic BH4 or sepiapterin 6.Current participation in any other investigational drug study or use of any investigational agent within 30 days prior to Screening 7.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 8.A female who is pregnant or breastfeeding, or considering pregnancy 9.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 10.Past medical history and/or evidence of renal impairment and/or condition including moderate/severe renal insufficiency (glomerular filtration rate [GFR] <60 mL/min) and/or under care of a nephrologist 11.Any abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated GFR <60 mL/min/1.73m2. In subjects =18 years of age, the Modification of Diet in Renal Disease Equation should be used to determine GFR. In subjects <18 years, the Bedside Schwartz Equation should be used to determine GFR. 12.Requirement for concomitant treatment with any drug known to inhibit folate synthesis (eg, methotrexate) 13.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 14.Major surgery within the prior 90 days of screening 15.Concomitant treatment with BH4 supplementation (eg, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ) 16.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 efficacy of PTC923 in reducing blood Phe levels in subjects with PKU as measured by mean change in blood Phe levels from baseline to Weeks 5 and 6 (ie, the average of each respective treatment dose 2-week period of double-blind treatment);Secondary Objective: •To evaluate the proportion of subjects with baseline Phe levels =600 µmol/L who achieve Phe levels <600 µmol/L at the end of the double-blind treatment period •To evaluate the effect of PTC923 dose response on reducing blood Phe levels in subjects with PKU •To evaluate the PK of PTC923 in subjects with PKU •To assess the safety of PTC923 in subjects with PKU;Primary end point(s): The primary efficacy measure will be reduction in blood Phe levels in subjects with PKU as measured by mean change in Phe levels from baseline to Part 2 Weeks 5 and 6 (ie, the average of the 2-week period at the target dose of double-blind treatment). Baseline blood Phe level will be the mean of Day -1 and Day 1 (predose) blood Phe levels;Timepoint(s) of evaluation of this end point: Weeks 5 and 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are the proportion of subjects with baseline Phe levels =600 µmol/L who achieve Phe levels <600 µmol/L at the end of the double-blind treatment period and the change from baseline in mean blood Phe levels at each PTC923 dose level (ie, each 2-week period in Part 2).;Timepoint(s) of evaluation of this end point: each 2-week period in Part 2 | — |
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