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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05166161




Registration number
NCT05166161
Ethics application status
Date submitted
8/12/2021
Date registered
21/12/2021
Date last updated
8/10/2024

Titles & IDs
Public title
A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria
Scientific title
A Phase 3 Open-Label Study of PTC923 (Sepiapterin) in Phenylketonuria
Secondary ID [1] 0 0
2021-000497-28
Secondary ID [2] 0 0
PTC923-MD-004-PKU
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Phenylketonuria 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PTC923

Experimental: PTC923 - Participants will receive PTC923 7.5 mg/kg (participants 0 to \<6 months of age), 15 mg/kg (participants 6 to \<12 months of age), 30 mg/kg (participants 12 months to \<2 years of age), or 60 mg/kg (participants =2 years of age) orally once daily for a minimum of 12 months or until participant experiences lack of efficacy, adverse events (AEs) that lead to discontinuation, withdraws from treatment, or PTC923 is authorized and commercially available in the specific country.


Treatment: Drugs: PTC923
PTC923 powder for oral use will be suspended in water or apple juice prior to administration.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Baseline up to end of study (up to approximately 2.5 years)
Primary outcome [2] 0 0
Change From Baseline in Dietary Phe/Protein Consumption at Week 26, Measured During Phe Tolerance Assessment Period
Timepoint [2] 0 0
Baseline, Week 26
Secondary outcome [1] 0 0
Change From Baseline in Quality of Life (QOL) Using Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire at Months 8, 14, 20, 26, 32, and 38
Timepoint [1] 0 0
Baseline, Months 8, 14, 20, 26, 32, and 38
Secondary outcome [2] 0 0
Change From Baseline in QOL Using the European Quality of Life - 5 Dimensions (EQ-5D) at Months 8, 14, 20, 26, 32, and 38
Timepoint [2] 0 0
Baseline, Months 8, 14, 20, 26, 32, and 38

Eligibility
Key inclusion criteria
* Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by past medical history of at least 2 blood Phe measurements =600 µmol/L.
* Women of childbearing potential must have a negative pregnancy test at screening and agree to abstinence or the use of at least one highly effective form of contraception for the duration of the study, and for up to 90 days after the last dose of the study drug.
* 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.
* Willing to continue current diet unchanged while participating in the study (unless specifically instructed to change diet during the study by the investigator).
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inability to tolerate oral medication.
* A female who is pregnant or breastfeeding, or considering pregnancy.
* Serious neuropsychiatric illness (for example, 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.
* Past medical history and/or evidence of renal impairment and/or condition including moderate/severe renal insufficiency (glomerular filtration rate [GFR] <60 milliliters [mL]/minute [min] min as estimated most recently during qualifying participation in a feeder study) and/or under care of a nephrologist.
* Any other condition 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.
* Requirement for concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate).
* Concomitant treatment with tetrahydrobiopterin (BH4) supplementation (for example, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).

Additional criteria for non-feeder participants 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.
* History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy.
* History of allergies or adverse reactions to synthetic BH4 or sepiapterin.
* Any clinically significant laboratory abnormality as determined by the investigator.
* Any abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated GFR <60 milliliters (mL)/minute/1.73 square meter (m^2).

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2026
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
PARC Clinical Research - Adelaide
Recruitment hospital [3] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
SA 5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Brazil
State/province [8] 0 0
Rio Grande Do Sul
Country [9] 0 0
Brazil
State/province [9] 0 0
São Paulo
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Denmark
State/province [12] 0 0
Copenhagen
Country [13] 0 0
Georgia
State/province [13] 0 0
Tbilisi
Country [14] 0 0
Germany
State/province [14] 0 0
Hamburg
Country [15] 0 0
Germany
State/province [15] 0 0
Heidelberg
Country [16] 0 0
Germany
State/province [16] 0 0
Münster
Country [17] 0 0
Italy
State/province [17] 0 0
Veneto
Country [18] 0 0
Italy
State/province [18] 0 0
Rome
Country [19] 0 0
Japan
State/province [19] 0 0
Multiple Locations
Country [20] 0 0
Mexico
State/province [20] 0 0
Jalisco
Country [21] 0 0
Netherlands
State/province [21] 0 0
Groningen
Country [22] 0 0
Portugal
State/province [22] 0 0
Douro Litoral
Country [23] 0 0
Portugal
State/province [23] 0 0
Estremadura
Country [24] 0 0
Spain
State/province [24] 0 0
Esplugues De Llobregat
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
Turkey
State/province [26] 0 0
Ankara
Country [27] 0 0
Turkey
State/province [27] 0 0
Istanbul
Country [28] 0 0
Turkey
State/province [28] 0 0
Izmir
Country [29] 0 0
Turkey
State/province [29] 0 0
Adana
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Birmingham
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
PTC Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The main purpose of this study is to evaluate the long-term safety of PTC923 in participants with phenylketonuria, and to evaluate the changes from baseline in dietary phenylalanine (Phe)/protein consumption.
Trial website
https://clinicaltrials.gov/study/NCT05166161
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patient Advocacy
Address 0 0
Country 0 0
Phone 0 0
1-866-562-4620
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05166161