(S)-2-AMINO-6-(2-HYDROXYPROPANOYL)-7,8-DIHYDROPTERIDIN-4(3H)-ONE for Phenylketonuria (PKU)

Inclusion criteria

• {"criterion_text":"- Informed consent and assent (if necessary, at the investigator’s discretion [ie, for children]) with parental/legal guardian consent"}
• {"criterion_text":"- Male or female subjects of any age"}
• {"criterion_text":"- Clinical diagnosis of PKU with HPA documented by past medical history of at least 2 blood Phe measurements ≥600 μmol/L"}
• {"criterion_text":"- Women of childbearing potential, as defined in the Clinical Trial Facilitation Group guidance (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 <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 occlusion • 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Willing and able to comply with the protocol and study procedures."}
• {"criterion_text":"- Willing to continue current diet unchanged while participating in the study (unless specifically instructed to change diet during the study by the investigator)."}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- The individual, in the opinion of the investigator, is unwilling or unable to adhere to the requirements of the study"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: History of allergies or adverse reactions to synthetic BH4 or sepiapterin"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: Current participation in any other investigational drug study or use of any investigational agent within 30 days prior to Screening"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: 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"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: 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."}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: 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"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: Major surgery within the prior 90 days of screening"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: Unwillingness to washout from BH4 supplementation (eg, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ)"}
• {"criterion_text":"- Inability to tolerate oral medication"}
• {"criterion_text":"- A female who is pregnant or breastfeeding, or considering pregnancy"}
• {"criterion_text":"- Serious neuropsychiatric illness (eg, major depression) not currently under medical control, that in the opinion of the investigator or PTC, would interfere with the subject’s ability to participate in the study or increase the risk of participation for that subject"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Any other condition that in the opinion of the investigator or PTC, would interfere with the subject’s ability to participate in the study or increase the risk of participation for that subject"}
• {"criterion_text":"- Requirement for concomitant treatment with any drug known to inhibit folate synthesis (eg, methotrexate)"}
• {"criterion_text":"- Concomitant treatment with BH4 supplementation (eg, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ)"}
• {"criterion_text":"- Additional criteria for subjects who did not participate in a feeder study: 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"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured by number of treatment-emergent adverse events (TEAEs), assessment of severity of TEAEs, clinical laboratory tests, vital signs, and physical examinations."}
• {"endpoint_text":"- The primary efficacy endpoint is the change from baseline in dietary Phe/protein consumption measured during Dietary Phe Tolerance Assessment period.","definition_or_measurement_approach":"Change from baseline in dietary phenylalanine (Phe)/protein consumption measured during the Dietary Phe Tolerance Assessment period."}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Quality of life assessed using PKU-QOL instrument in language-appropriate subset; age-specific PKU-QOL versions applied (parent proxy for ages 6-8, child 9-11, adolescent 12-17, adult ≥18)."}
• {"endpoint_text":"- 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])","definition_or_measurement_approach":"Quality of life assessed using EQ-5D instruments appropriate by age: EQ-5D-Y proxy 3-7 yrs, EQ-5D-Y 8-15 yrs, EQ-5D-5L ≥16 yrs."}
• {"endpoint_text":"- PK assessment of sepiapterin and BH4 concentrations in plasma following dosing of sepiapterin","definition_or_measurement_approach":"Pharmacokinetic assessment measuring plasma concentrations of sepiapterin and tetrahydrobiopterin (BH4) following PTC923 dosing."}
• {"endpoint_text":"- Acceptability scores (<12 years); taste and palatability scores (<18 years)","definition_or_measurement_approach":"Acceptability and palatability/taste measured by study-specific scores for participants <12 years (acceptability) and <18 years (taste/palatability assessments)."}

France

Latest Decision Or Authorization Date

18-10-2024

Number Of Sites

2

Number Of Participants

10

Portugal

Latest Decision Or Authorization Date

05-02-2024

Number Of Sites

3

Number Of Participants

4

Denmark

Latest Decision Or Authorization Date

02-02-2024

Number Of Sites

1

Number Of Participants

3

Italy

Latest Decision Or Authorization Date

12-02-2024

Number Of Sites

2

Number Of Participants

4

Netherlands

Latest Decision Or Authorization Date

02-02-2024

Number Of Sites

1

Number Of Participants

8

Spain

Latest Decision Or Authorization Date

05-02-2024

Number Of Sites

3

Number Of Participants

7

Czechia

Latest Decision Or Authorization Date

24-10-2024

Number Of Sites

1

Number Of Participants

6

Germany

Latest Decision Or Authorization Date

05-02-2024

Number Of Sites

3

Number Of Participants

14

Slovenia

Latest Decision Or Authorization Date

01-10-2024

Number Of Sites

1

Number Of Participants

6

Poland

Latest Decision Or Authorization Date

11-11-2024

Number Of Sites

2

Number Of Participants

18

Primary sponsor

Full Name

PTC Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

codes: 4

Name

Icon Development Solutions LLC

Responsibilities

codes: 4

Name

Novotech Clinical Research (Cyprus) Limited

Responsibilities

codes: 1|5

Third parties

• {"country":"United States","full_name":"Inclin Inc.","duties_or_roles":"codes: 2|6","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"York Bioanalytical Solutions Limited","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Cyprus","full_name":"Novotech Clinical Research (Cyprus) Limited","duties_or_roles":"codes: 1|5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Australia","full_name":"Agilex Biolabs Pty Limited","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}