A Phase 3 Study of PTC923 in Subjects with Phenylketonuria

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 178

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 <1% per year when used consistently and correctly):
•Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- Oral
- Intravaginal
- Transdermal
•Progestogen-only hormonal contraception associated with inhibition of ovulation:
- Oral
- Injectable
- Implantable
•Intrauterine device
•Intrauterine hormone-releasing system
•Bilateral tubal ligation
•Vasectomized partner with confirmed azoospermia
Highly effective contraception or abstinence must be continued for the duration of the study, and for up to 90 days after the last dose of the study drug.
All females will be considered of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group without other known or suspected cause) or have been permanently sterilized surgically (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
6.Males who are sexually active with women of childbearing potential who have not had a vasectomy must agree to use a barrier method of birth control during the study and for up to 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period.
Males who are abstinent will not be required to use a contraceptive method unless they become sexually active. Males who have undergone a vasectomy are not required to use a contraceptive method if at least 16 weeks post procedure.
7.Willing and able to comply with the protocol and study procedures
8.Willing to continue current diet unchanged while participating in the study

Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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Updated 1/30/2023