A phase 3 study of PTC923 in subjects with phenylketonuria

Phase 3

Completed

Conditions: hyperphenylalaninemia
Phenylketonuria
10037008

Registration Number: NL-OMON51999

Lead Sponsor: PTC Therapeutics Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

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 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).
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

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-alphacarbinolamine
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

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy measure will be reduction in blood Phe levels in subjects<br /><br>with PKU as measured by mean change in Phe levels from baseline to Part 2 Weeks<br /><br>5 and 6 (ie, the average of the 2-week period at the target dose of<br /><br>double-blind treatment). Baseline blood Phe level will be the mean of Day -1<br /><br>and Day 1 blood Phe levels.</p><br>

Secondary Outcome Measures