A Phase 3 Study of PTC923 (Sepiapterin) in Subjects with Phenylketonuria

Phase 1

• Conditions: Metabolic Disorders - Phenylketonuria; MedDRA version: 20.0Level: LLTClassification code 10034873Term: Phenylketonuria (PKU)System Organ Class: 100000004850; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2021-000497-28-DE
• Lead Sponsor: PTC Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-12-22
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Informed consent and assent (if necessary, at the investigator’s discretion [ie, for children
and/or subjects that are mentally impaired secondary to disease]) 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
3. 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 <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).
4. 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.
5. Willing and able to comply with the protocol and study procedure
6. Willing to continue current diet unchanged while participating in the study (unless
specifically instructed to change diet during the study by the investigator)
Are the trial subjects under 18? yes
Number of subjects for this age range: 200
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. 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified