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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05154890




Registration number
NCT05154890
Ethics application status
Date submitted
20/08/2021
Date registered
13/12/2021
Date last updated
27/07/2023

Titles & IDs
Public title
A Multiple Ascending Dose Study of ACN00177 (Pegtarviliase) in Subjects With CBS Deficiency
Scientific title
A Phase 1/2 Multiple Ascending-Dose Study in Subjects With Homocystinuria Due to Cystathionine ß-Synthase (CBS) Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of ACN00177
Secondary ID [1] 0 0
2019-004791-19
Secondary ID [2] 0 0
CACN00177-100D
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Homocystinuria Due to Cystathionine Beta-Synthase Deficiency 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

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

Experimental: Pegtarviliase Cohort 1 - Planned for 4 subjects =18 years of age dosing at Dose A weekly for a total of 4 doses

Experimental: Pegtarviliase Cohort 2 - Planned for 4 subjects =12 years of age dosing at Dose B weekly for a total of 4 doses

Experimental: Pegtarviliase Cohort 3 - Planned for 4 subjects =12 years of age (=18 in the US) dosing at Dose C weekly for a total of 4 doses

Experimental: Pegtarviliase Cohort 4 - Planned for 4 subjects =12 years of age (=18 in the US) dosing at Dose D weekly for a total of 4 doses

Experimental: Pegtarviliase Cohort 5 - Optional cohort for up to 12 subjects =12 years of age (=18 in the US) dosing at Dose E weekly for a total of 13 doses


Treatment: Drugs: Pegtarviliase IV
Administered IV

Treatment: Drugs: Pegtarviliase SC
Administered SC
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events
Timepoint [1] 0 0
Reporting will be from signing consent through study completion, an average of 70 days
Secondary outcome [1] 0 0
Pharmacokinetic Profile of IV pegtarviliase Cmax
Timepoint [1] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [2] 0 0
Pharmacokinetic Profile of IV pegtarviliase AUC
Timepoint [2] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [3] 0 0
Pharmacokinetic Profile of IV pegtarviliase Tmax
Timepoint [3] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [4] 0 0
Pharmacokinetic Profile of IV pegtarviliase T1/2
Timepoint [4] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [5] 0 0
Pharmacokinetic Profile of Subcutaneous pegtarviliase Cmax
Timepoint [5] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [6] 0 0
Pharmacokinetic Profile of Subcutaneous pegtarviliase AUC
Timepoint [6] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [7] 0 0
Pharmacokinetic Profile of Subcutaneous pegtarviliase Tmax
Timepoint [7] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [8] 0 0
Pharmacokinetic Profile of Subcutaneous pegtarviliase T 1/2
Timepoint [8] 0 0
At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Secondary outcome [9] 0 0
Changes in total plasma homocysteine after treatment with pegtarviliase
Timepoint [9] 0 0
At Visit Day 29
Secondary outcome [10] 0 0
Time course of tHcy change after pegtarviliase administration and reversibility upon follow up post dosing
Timepoint [10] 0 0
Weekly, baseline through study completion, up to 12 weeks

Eligibility
Key inclusion criteria
1. Diagnosis of homocystinuria due to CBS deficiency
2. Capable of providing signed informed consent/assent and to comply with all study related procedures
3. Is =12 years of age (=18 in the US) at the time of signing the informed consent/assent
4. Plasma tHcy =50 µM (rounded to the nearest whole number) and documentation of previous tHcy =80 µM
5. Female subjects of child-bearing potential must have a negative serum pregnancy test during the screening period and a negative urine pregnancy test prior to dosing on the first day of treatment
6. If the subject (male or female) is engaging in sexual activity, he/she must be unable to become pregnant/cause pregnancy or must agree to use highly effective contraception
7. Subjects receiving pyridoxine and/or betaine must be on the same dose of the medication(s) for at least 6 weeks prior to the first administration of study drug and be willing and able to remain on a stable dose for the duration of the study. Similarly, those on prescribed dietary therapy must be on a consistent dietary regimen for at least 6 weeks prior to study drug and should maintain this regimen for the duration of the study
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Other medical conditions or co-morbidity(ies) that, in the opinion of the investigator, would put the subject at increased medical risk or interfere with study compliance or data interpretation (eg, severe intellectual disability that precludes completion of the required study assessments)
2. Currently participating in another therapeutic clinical study or has received any investigational agent within 30 days or 5 half-lives, whichever is longer, prior to the first dose of study drug in this study
3. Surgery requiring general anesthesia within 8 weeks prior to the first dose of study drug or planned surgery druing the treatment period
4. Active infection requiring anti-infective therapy <2 weeks prior to the first dose of study drug in this study; anti-infective therapy that completes =2 weeks prior to first dose of study drug is acceptable
5. Pregnant or nursing
6. Females of child-bearing potential who are using or plan to use estrogen-containing contraception during the study (unless the subject currently using estrogen-containing contraceptives is willing to switch to a non-estrogen-containing contraceptive at least 1 week before dosing and for the duration of the study) and for 30 days after the last dose
7. History of hypersensitivity to polyethylene glycol (PEG) that, in the judgment of the investigator, puts the subject at unacceptable risk for adverse events (AEs)
8. Serum creatinine level >1.5× the upper limit of normal (ULN)
9. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin level > 2× the ULN

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/04/2023
Sample size
Target
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Birmingham
Country [3] 0 0
United Kingdom
State/province [3] 0 0
London
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Aeglea Biotherapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety and tolerability of pegtarviliase in approximately 36 subjects with homocystinuria due to CBS deficiency.
Trial website
https://clinicaltrials.gov/study/NCT05154890
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Cortney Caudill
Address 0 0
Aeglea Biotherapeutics
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/NCT05154890