A Multiple Ascending Dose Study of ACN00177 (Pegtarviliase) in Subjects With CBS Deficiency

NCT05154890 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: CACN00177-100D2019-004791-19
• Study Type: interventional
• Target: 13
• Locations: 3 countries
• Sites: 9

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.

Conditions

Homocystinuria Due to Cystathionine Beta-Synthase Deficiency

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events

  Incidence of treatment-emergent adverse events

  Reporting will be from signing consent through study completion, an average of 70 days

Secondary Outcomes (10)

• Pharmacokinetic Profile of IV pegtarviliase Cmax

  At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours

• Pharmacokinetic Profile of IV pegtarviliase AUC

  At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours

• Pharmacokinetic Profile of IV pegtarviliase Tmax

  At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours

• Pharmacokinetic Profile of IV pegtarviliase T1/2

  At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours

• Pharmacokinetic Profile of Subcutaneous pegtarviliase Cmax

  At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours

Study Arms (5)

Pegtarviliase Cohort 1

EXPERIMENTAL

Planned for 4 subjects ≥18 years of age dosing at Dose A weekly for a total of 4 doses

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

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

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

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

Drug: Pegtarviliase SC

Interventions

Pegtarviliase IV DRUG

Administered IV

Also known as: ACN00177

Pegtarviliase Cohort 1

Pegtarviliase SC DRUG

Administered SC

Also known as: ACN00177

Pegtarviliase Cohort 2; Pegtarviliase Cohort 3; Pegtarviliase Cohort 4; Pegtarviliase Cohort 5

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Aeglea Biotherapeutics: lead

Study Sites (9)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Westmead Hospital

Westmead, New South Wales, Australia

Location

Royal Children's Hospital

Parkville, Victoria, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, Australia

Location

University Hospitals Birmingham NHS

Birmingham, United Kingdom

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Guy's and St Thomas' Hospital NHS Foundation Trust

London, United Kingdom

Location

University College London

London, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Location

MeSH Terms

Conditions

Homocystinuria

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hyperhomocysteinemia; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Cortney Caudill

  Aeglea Biotherapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: December 13, 2021
• Study Start: May 13, 2021
• Primary Completion: April 21, 2023
• Study Completion: April 21, 2023
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

US (1); AU (3); GB (5)