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

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05154890
Recruitment Status : Recruiting
First Posted : December 13, 2021
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
Aeglea Biotherapeutics

Tracking Information
First Submitted Date  ICMJE August 20, 2021
First Posted Date  ICMJE December 13, 2021
Last Update Posted Date January 17, 2023
Actual Study Start Date  ICMJE May 13, 2021
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2021)		 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2023)
  • Pharmacokinetic Profile of IV pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Cmax
  • Pharmacokinetic Profile of IV pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    AUC
  • Pharmacokinetic Profile of IV pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Tmax
  • Pharmacokinetic Profile of IV pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    T1/2
  • Pharmacokinetic Profile of Subcutaneous pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Cmax
  • Pharmacokinetic Profile of Subcutaneous pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    AUC
  • Pharmacokinetic Profile of Subcutaneous pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Tmax
  • Pharmacokinetic Profile of Subcutaneous pegtarviliase [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    T1/2
  • Changes in total plasma homocysteine after treatment with pegtarviliase [ Time Frame: At Visit Day 29 ]
    Changes in total plasma homocysteine after treatment with pegtarviliase
  • 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 ]
    Time course of tHcy change after pegtarviliase administration and reversibility upon follow up post dosing
Original Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2021)
  • Pharmacokinetic Profile of IV ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Cmax
  • Pharmacokinetic Profile of IV ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    AUC
  • Pharmacokinetic Profile of IV ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Tmax
  • Pharmacokinetic Profile of IV ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    T1/2
  • Pharmacokinetic Profile of Subcutaneous ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Cmax
  • Pharmacokinetic Profile of Subcutaneous ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    AUC
  • Pharmacokinetic Profile of Subcutaneous ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    Tmax
  • Pharmacokinetic Profile of Subcutaneous ACN00177 [ Time Frame: At pre-dose, 1hour, 6hours, 24hours, 48hours, 72hours, 96hours and 120hours ]
    T1/2
  • Changes in total plasma homocysteine after treatment with ACN00177 [ Time Frame: At Visit Day 29 ]
    Changes in total plasma homocysteine after treatment with ACN00177
  • Time course of tHcy change after ACN00177 administration and reversibility upon follow up post dosing [ Time Frame: Weekly, baseline through follow-up for a total of 7 occurrences ]
    Time course of tHcy change after ACN00177 administration and reversibility upon follow up post dosing
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multiple Ascending Dose Study of ACN00177 (Pegtarviliase) in Subjects With CBS Deficiency
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Homocystinuria Due to Cystathionine Beta-Synthase Deficiency
Intervention  ICMJE
  • Drug: Pegtarviliase
    Administered IV
    Other Name: ACN00177
  • Drug: Pegtarviliase
    Administered SC
    Other Name: ACN00177
Study Arms  ICMJE
  • Experimental: Pegtarviliase Cohort 1
    Planned for 4 subjects ≥18 years of age dosing at Dose A weekly for a total of 4 doses
    Intervention: Drug: Pegtarviliase
  • Experimental: Pegtarviliase Cohort 2
    Planned for 4 subjects ≥12 years of age dosing at Dose B weekly for a total of 4 doses
    Intervention: Drug: Pegtarviliase
  • 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
    Intervention: Drug: Pegtarviliase
  • 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
    Intervention: Drug: Pegtarviliase
  • 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
    Intervention: Drug: Pegtarviliase
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 12, 2023)		 36
Original Estimated Enrollment  ICMJE
 (submitted: November 30, 2021)		 25
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Aeglea Clinical Department 1.855.509.9921 clinicaltrials@aegleabio.com
Contact: Josie Gayton
Listed Location Countries  ICMJE Australia,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05154890
Other Study ID Numbers  ICMJE CACN00177-100D
2019-004791-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Aeglea Biotherapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Aeglea Biotherapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Reena Sharma, MD Northern Care Alliance NHS Foundation Trust
PRS Account Aeglea Biotherapeutics
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP