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A Phase 3, Randomized, Crossover, Open-Label, Active-Controlled Study of Sepiapterin versus Sapropterin in Participants With Phenylketonuria ≥2 years of Age
EU CTIS ID: 2023-506238-61-00
What this study is testing
To compare the efficacy of sepiapterin to sapropterin in reducing blood Phe levels in participants with PKU
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Informed consent, and if necessary, assent (with parent/legally designated representative consent)
- Male or female participants ≥2 years of age
- Blood Phe level ≥360 μmol/L on current therapy anytime during Screening and blood Phe level ≥360 μmol/L on current therapy when taking the average of the 3 most recent Phe levels from the participant’s medical history (inclusive of the Screening value)
- Clinical diagnosis of PKU with hyperphenylalaninemia documented by past medical history of at least 2 blood Phe measurements ≥600 μmol/L
- 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 ie, fertile, following menarche and until becoming 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).
- 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.
You likely can't join if
- The individual, in the opinion of the investigator, is unwilling or unable to adhere to the requirements of the study. Incapacitated adults are not eligible for participation in this study.
- 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
- 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 participants ≥18 years of age, the Modification of Diet in Renal Disease Equation should be used to determine GFR. In participants <18 years, the Bedside Schwartz Equation should be used to determine GFR.
- Requirement for concomitant treatment with levodopa or with any drug known to inhibit folate synthesis (eg, methotrexate)
- Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive guanosine triphosphate (GTP) cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin 4-alpha-carbinolamine dehydratase genes
- Major surgery within the prior 90 days of Screening
See the full eligibility criteria
Who can join
- Informed consent, and if necessary, assent (with parent/legally designated representative consent)
- Male or female participants ≥2 years of age
- Blood Phe level ≥360 μmol/L on current therapy anytime during Screening and blood Phe level ≥360 μmol/L on current therapy when taking the average of the 3 most recent Phe levels from the participant’s medical history (inclusive of the Screening value)
- Clinical diagnosis of PKU with hyperphenylalaninemia documented by past medical history of at least 2 blood Phe measurements ≥600 μmol/L
- 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 ie, fertile, following menarche and until becoming 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).
- 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.
- Willing and able to comply with the protocol and study procedures
- Willing to continue current diet unchanged while participating in the study
What rules you out
- The individual, in the opinion of the investigator, is unwilling or unable to adhere to the requirements of the study. Incapacitated adults are not eligible for participation in this study.
- 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
- 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 participants ≥18 years of age, the Modification of Diet in Renal Disease Equation should be used to determine GFR. In participants <18 years, the Bedside Schwartz Equation should be used to determine GFR.
- Requirement for concomitant treatment with levodopa or with any drug known to inhibit folate synthesis (eg, methotrexate)
- Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive guanosine triphosphate (GTP) cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin 4-alpha-carbinolamine dehydratase genes
- Major surgery within the prior 90 days of Screening
- Unwillingness to washout from BH4 supplementation (eg, sapropterin, KUVAN).
- Use of pegvaliase-pqpz (PALYNZIQ) concurrently or within the 60 days prior to Screening
- Greater than 20% variance in dietary Phe consumption as measured by mandatory weekly 3 day diet record collection for 4 consecutive weeks (Dietary Control Observation Period during Screening)
- Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, peptic ulcer disease, etc.) that could affect the absorption of study drug
- History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy
- Inability to tolerate oral medication
- History of allergies or adverse reactions to any of the ingredients or excipients of synthetic BH4 or sepiapterin
- Current participation in any other investigational drug study or use of any investigational agent within 30 days prior to Screening
- 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
- A female who is pregnant or breastfeeding, or considering pregnancy
- Serious neuropsychiatric illness (eg, major depression) not currently under medical control, that in the opinion of the investigator or sponsor would interfere with the participant’s ability to participate in the study or increase the risk of participation for that participant
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- Australia
- Georgia
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; Australia; Georgia; United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.