Homocystinuria Due to Cystathionine Beta-Synthase DeficiencyPhase 1/2NCT05154890
A Multiple Ascending Dose Study of ACN00177 (Pegtarviliase) in Subjects With CBS Deficiency
A Phase 1/2 study testing Pegtarviliase IV and Pegtarviliase SC in people with Homocystinuria Due to Cystathionine Beta-Synthase Deficiency, run by Aeglea Biotherapeutics at 9 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Homocystinuria Due to Cystathionine Beta-Synthase Deficiency
- What is being tested?
- Pegtarviliase IV and Pegtarviliase SC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 13 May 2021to 21 Apr 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of homocystinuria due to CBS deficiency
- Capable of providing signed informed consent/assent and to comply with all study related procedures
- Is ≥12 years of age (≥18 in the US) at the time of signing the informed consent/assent
- Plasma tHcy ≥50 µM (rounded to the nearest whole number) and documentation of previous tHcy ≥80 µM
- 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
- 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
- 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
Who cannot join
- 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)
- 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
- Surgery requiring general anesthesia within 8 weeks prior to the first dose of study drug or planned surgery druing the treatment period
- 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
- Pregnant or nursing
- 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
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- History of hypersensitivity to polyethylene glycol (PEG) that, in the judgment of the investigator, puts the subject at unacceptable risk for adverse events (AEs)
- Serum creatinine level >1.5× the upper limit of normal (ULN)
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin level > 2× the ULN
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United Kingdom5 sites
University Hospitals Birmingham NHS
Birmingham
Great Ormond Street Hospital
London
Guy's and St Thomas' Hospital NHS Foundation Trust
London
University College London
London
Salford Royal NHS Foundation Trust
Salford
Australia3 sites
Royal Children's Hospital
Parkville, Victoria
Royal Melbourne Hospital
Parkville, Victoria
Westmead Hospital
Westmead, New South Wales
About this study
Official title: A Phase 1/2 Multiple Ascending-Dose Study in Subjects With Homocystinuria Due to Cystathionine β-Synthase (CBS) Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of ACN00177
The purpose of this study is to evaluate the safety and tolerability of pegtarviliase in approximately 36 subjects with homocystinuria due to CBS deficiency.
Read the detailed description
The purpose of this Phase 1/2 study is to evaluate the safety, pharmacokinetics and pharmacodynamics of multiple ascending doses of pegtarviliase in subjects with homocystinuria due to CBS deficiency. The study is composed of 2 parts: Part 1: a single IV (intravenous) cohort with 4 once-weekly (QW) doses of study drug and Part 2: three SC (subcutaneous) cohorts with 4 QW doses of study drug, with an optional fifth.
- Being tested
- Pegtarviliase IV, Pegtarviliase SC
- Medical subject headings
- Homocystinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pegtarviliase IVDrug
Also called ACN00177
Administered IV
Pegtarviliase SCDrug
Also called ACN00177
Administered SC
| Study group | Role | What they receive |
|---|---|---|
| Pegtarviliase Cohort 1 | Experimental | Planned for 4 subjects ≥18 years of age dosing at Dose A weekly for a total of 4 doses Receives: Drug: Pegtarviliase IV |
| Pegtarviliase Cohort 2 | Experimental | Planned for 4 subjects ≥12 years of age dosing at Dose B weekly for a total of 4 doses Receives: Drug: Pegtarviliase SC |
| Pegtarviliase Cohort 3 | Experimental | Planned for 4 subjects ≥12 years of age (≥18 in the US) dosing at Dose C weekly for a total of 4 doses Receives: Drug: Pegtarviliase SC |
| Pegtarviliase Cohort 4 | Experimental | Planned for 4 subjects ≥12 years of age (≥18 in the US) dosing at Dose D weekly for a total of 4 doses Receives: Drug: Pegtarviliase SC |
| Pegtarviliase Cohort 5 | Experimental | 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 Receives: Drug: Pegtarviliase SC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events
Incidence of treatment-emergent adverse events
Measured: Reporting will be from signing consent through study completion, an average of 70 days
Secondary outcomes (10)
Pharmacokinetic Profile of IV pegtarviliase Cmax
Cmax
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of IV pegtarviliase AUC
AUC
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of IV pegtarviliase Tmax
Tmax
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of IV pegtarviliase T1/2
T1/2
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase Cmax
Cmax
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase AUC
AUC
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase Tmax
Tmax
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase T 1/2
T1/2
Measured: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Changes in total plasma homocysteine after treatment with pegtarviliase
Changes in total plasma homocysteine after treatment with pegtarviliase
Measured: At Visit Day 29
Time course of tHcy change after pegtarviliase administration and reversibility upon follow up post dosing
Time course of tHcy change after pegtarviliase administration and reversibility upon follow up post dosing
Measured: Weekly, baseline through study completion, up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2021
- Study start13 May 2021
- Primary completion21 Apr 2023
- Study completion21 Apr 2023
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Homocystinuria Due to Cystathionine Beta-Synthase DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeglea Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cortney Caudill, Study director, Aeglea Biotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05154890
- Sponsor's protocol ID
- CACN00177-100D
- Other IDs
- 2019-004791-19, 2019
- Status last verified
- Jul 2023
- First submitted
- 20 Aug 2021
- Last updated
- 27 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Multiple Ascending-Dose Study in Subjects With Homocystinuria Due to Cystathionine β-Synthase (CBS) Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of ACN00177
- ClinicalTrials.gov ID
- NCT05154890
- Acronym / sponsor ID
- CACN00177-100D
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Aeglea BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 13 May 2021 (actual)
- Primary completion
- 21 Apr 2023 (actual)
- Study completion
- 21 Apr 2023 (actual)
- First posted
- 13 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of pegtarviliase in approximately 36 subjects with homocystinuria due to CBS deficiency.
Detailed description
The purpose of this Phase 1/2 study is to evaluate the safety, pharmacokinetics and pharmacodynamics of multiple ascending doses of pegtarviliase in subjects with homocystinuria due to CBS deficiency. The study is composed of 2 parts: Part 1: a single IV (intravenous) cohort with 4 once-weekly (QW) doses of study drug and Part 2: three SC (subcutaneous) cohorts with 4 QW doses of study drug, with an optional fifth.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Pegtarviliase Cohort 1 | Experimental | Drug: Pegtarviliase IVPlanned for 4 subjects ≥18 years of age dosing at Dose A weekly for a total of 4 doses |
| Pegtarviliase Cohort 2 | Experimental | Drug: Pegtarviliase SCPlanned for 4 subjects ≥12 years of age dosing at Dose B weekly for a total of 4 doses |
| Pegtarviliase Cohort 3 | Experimental | Drug: Pegtarviliase SCPlanned for 4 subjects ≥12 years of age (≥18 in the US) dosing at Dose C weekly for a total of 4 doses |
| Pegtarviliase Cohort 4 | Experimental | Drug: Pegtarviliase SCPlanned for 4 subjects ≥12 years of age (≥18 in the US) dosing at Dose D weekly for a total of 4 doses |
| Pegtarviliase Cohort 5 | Experimental | Drug: Pegtarviliase SCOptional 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 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of homocystinuria due to CBS deficiency
- Capable of providing signed informed consent/assent and to comply with all study related procedures
- Is ≥12 years of age (≥18 in the US) at the time of signing the informed consent/assent
- Plasma tHcy ≥50 µM (rounded to the nearest whole number) and documentation of previous tHcy ≥80 µM
- 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
Key exclusion criteria (9 listed)
- 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)
- 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
- Surgery requiring general anesthesia within 8 weeks prior to the first dose of study drug or planned surgery druing the treatment period
- 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
- Pregnant or nursing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pegtarviliase IVAlso: ACN00177Administered IV | Drug | Pegtarviliase Cohort 1 |
| Pegtarviliase SCAlso: ACN00177Administered SC | Drug | Pegtarviliase Cohort 2, Pegtarviliase Cohort 3, Pegtarviliase Cohort 4, Pegtarviliase Cohort 5 |
Primary outcome
Incidence of treatment-emergent adverse events
Time frame: Reporting will be from signing consent through study completion, an average of 70 days
Incidence of treatment-emergent adverse events
10 secondary outcomes
Pharmacokinetic Profile of IV pegtarviliase Cmax
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of IV pegtarviliase AUC
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of IV pegtarviliase Tmax
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of IV pegtarviliase T1/2
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase Cmax
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase AUC
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase Tmax
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Pharmacokinetic Profile of Subcutaneous pegtarviliase T 1/2
Time frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours
Changes in total plasma homocysteine after treatment with pegtarviliase
Time frame: At Visit Day 29
Time course of tHcy change after pegtarviliase administration and reversibility upon follow up post dosing
Time frame: Weekly, baseline through study completion, up to 12 weeks
Results and safety
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cortney Caudill study director
Aeglea Biotherapeutics
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pegtarviliase IV and Pegtarviliase SC in people with Homocystinuria Due to Cystathionine Beta-Synthase Deficiency, run by Aeglea Biotherapeutics at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom, Australia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events (time frame: Reporting will be from signing consent through study completion, an average of 70 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.