A phase 3 open-label study of PTC923 (Sepiapterin) in Phenylketonuria

Phase 3

• Conditions: hyperphenylalaninemia; Phenylketonuria; 10037008

• Registration Number: NL-OMON53510
• Lead Sponsor: PTC Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 8

Inclusion Criteria

Individuals are eligible to participate if they meet all the following
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 <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).
5. 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.
6. Willing and able to comply with the protocol and study procedures
7. Willing to continue current diet unchanged while participating in the study
(unless specifically instructed to change diet during the study by the
investigator)

Exclusion Criteria

Individuals are not eligible to participate if they meet any of the following
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
• Study Design: Not specified