Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05099640




Registration number
NCT05099640
Ethics application status
Date submitted
6/10/2021
Date registered
29/10/2021
Date last updated
10/01/2024

Titles & IDs
Public title
A Study of PTC923 in Participants With Phenylketonuria
Scientific title
A Phase 3 Study of PTC923 in Subjects With Phenylketonuria
Secondary ID [1] 0 0
2021-000474-29
Secondary ID [2] 0 0
PTC923-MD-003-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
Treatment: Drugs - Placebo

Experimental: Part 1: PTC923 - Participants will receive PTC923 7.5 milligrams (mg)/kilogram (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 14 days.

Experimental: Part 2: PTC923 - Participants will receive PTC923 20 mg/kg daily for Weeks 1 and 2, then PTC923 40 mg/kg daily for Weeks 3 and 4, then PTC923 60 mg/kg daily for Weeks 5 and 6.

Placebo comparator: Part 2: Placebo - Participants will receive equivalent quantities of placebo to match the 20 to 40 to 60 mg/kg dose escalation of the PTC923 treatment arm.


Treatment: Drugs: PTC923
PTC923 powder for oral use will be suspended in water or apple juice prior to administration.

Treatment: Drugs: Placebo
Placebo matching to PTC923
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 2 Double-blind Phase: Mean Change From Baseline in Blood Phenylketonuria (Phe) Level to Weeks 5 and 6 (Averaged Over a 2-week Period) in Participants With Phe Reduction From Baseline =30% During Part 1
Timepoint [1] 0 0
Baseline, Weeks 5 and 6 (average of the 2-week period)
Primary outcome [2] 0 0
Part 2 Double-blind Phase: Percent Change From Baseline in Blood Phe Level to Weeks 5 and 6 (Averaged Over a 2-week Period) in Participants With Phe Reduction From Baseline =30% During Part 1
Timepoint [2] 0 0
Baseline, Weeks 5 and 6 (average of the 2-week period)
Secondary outcome [1] 0 0
Part 2 Double-blind Phase: Percentage of Participants With Baseline Phe Levels =600 µmol/L Who Achieved Phe Levels <600 µmol/L in Participants With Phe Reduction From Baseline =30% During Part 1
Timepoint [1] 0 0
Weeks 5 and 6 (average of the 2-week period)
Secondary outcome [2] 0 0
Part 2 Double-blind Phase: Percentage of Participants With Baseline Phe Levels =360 µmol/L Who Achieved Phe Levels <360 µmol/L in Participants With Phe Reduction From Baseline =30% During Part 1
Timepoint [2] 0 0
Weeks 5 and 6 (average of the 2-week period)
Secondary outcome [3] 0 0
Part 2 Double-blind Phase: Mean Change From Baseline in Blood Phe Level at Each 2-Week Period (Averaged Over Each 2-Week Period) in Participants With Phe Reduction From Baseline =30% During Part 1
Timepoint [3] 0 0
Baseline, Weeks 1 and 2, Weeks 3 and 4, and Weeks 5 and 6 (average of each 2-week period)
Secondary outcome [4] 0 0
Part 2 Double-blind Phase: Percent Change From Baseline in Blood Phe Level at Each 2-Week Period (Averaged Over Each 2-Week Period) in Participants With Phe Reduction From Baseline =30% During Part 1
Timepoint [4] 0 0
Baseline, Weeks 1 and 2, Weeks 3 and 4, and Weeks 5 and 6 (average of each 2-week period)
Secondary outcome [5] 0 0
Part 1 Open-label Run-in Phase: Plasma Concentration of Tetrahydrobiopterin (BH4) and Sepiapterin
Timepoint [5] 0 0
Predose, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose at Day 1; 2 and 6 hours postdose at Day 14
Secondary outcome [6] 0 0
Part 2 Double-blind Phase: Plasma Concentration of BH4 and Sepiapterin
Timepoint [6] 0 0
Predose and 4 hours postdose at Days 1, 14, 28, and 42
Secondary outcome [7] 0 0
Part 1 Open-label Run-in Phase: Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24h) of Sepiapterin and BH4 Following the First Dose of Sepiapterin at 60 mg/kg
Timepoint [7] 0 0
0 to 24 hours postdose at Day 1
Secondary outcome [8] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [8] 0 0
Baseline up to Day 42

Eligibility
Key inclusion criteria
* 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 participant's medical history (inclusive of the screening value).
* Clinical diagnosis of phenylketonuria 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 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.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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 tetrahydrobiopterin (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.
* 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]) 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/1.73 square meter (m^2).
* Requirement for concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate).
* Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive guanosine-5'-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.
* Concomitant treatment with BH4 supplementation (for example, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).
* Unwillingness to washout from BH4 supplementation (for example, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/05/2023
Sample size
Target
Accrual to date
Final
157
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 Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
SA 5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Wisconsin
Country [11] 0 0
Brazil
State/province [11] 0 0
Rio Grande Do Sul
Country [12] 0 0
Brazil
State/province [12] 0 0
São Paulo
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Denmark
State/province [15] 0 0
Copenhagen
Country [16] 0 0
France
State/province [16] 0 0
Centre-Val De Loire
Country [17] 0 0
Georgia
State/province [17] 0 0
Tbilisi
Country [18] 0 0
Germany
State/province [18] 0 0
Hamburg
Country [19] 0 0
Germany
State/province [19] 0 0
Heidelberg
Country [20] 0 0
Germany
State/province [20] 0 0
Münster
Country [21] 0 0
Italy
State/province [21] 0 0
Lazio
Country [22] 0 0
Italy
State/province [22] 0 0
Veneto
Country [23] 0 0
Mexico
State/province [23] 0 0
Jalisco
Country [24] 0 0
Mexico
State/province [24] 0 0
Mexico City
Country [25] 0 0
Netherlands
State/province [25] 0 0
Groningen
Country [26] 0 0
Portugal
State/province [26] 0 0
Douro Litoral
Country [27] 0 0
Portugal
State/province [27] 0 0
Estremadura
Country [28] 0 0
Spain
State/province [28] 0 0
Esplugues De Llobregat
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Turkey
State/province [30] 0 0
Ankara
Country [31] 0 0
Turkey
State/province [31] 0 0
Istanbul
Country [32] 0 0
Turkey
State/province [32] 0 0
Izmir
Country [33] 0 0
Turkey
State/province [33] 0 0
Adana
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Birmingham
Country [35] 0 0
United Kingdom
State/province [35] 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 trial is to evaluate the efficacy of PTC923 in reducing blood phenylalanine (Phe) levels in participants with phenylketonuria as measured by mean change in blood Phe levels from baseline to Weeks 5 and 6 (that is, the average of each respective treatment dose 2-week period of double-blind treatment).
Trial website
https://clinicaltrials.gov/study/NCT05099640
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05099640