Homocystinuria Due to Cystathionine ß-Synthase (CBS) Deficiency MedDRA version: 20.0 Level: PT Classification code 10020365 Term: Homocystinuria System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: ACN00177
Pharmaceutical Form: Solution for injection
Sponsors
Aeglea Biotherapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of homocystinuria due to CBS deficiency 2. Capable of providing signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol 3. Is =12 years of age at the time of signing the informed consent/assent 4. Plasma 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 as specified in the full protocol 7. Subjects receiving pyridoxine and/or betaine must be on a stable 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 Are the trial subjects under 18? yes Number of subjects for this age range: 13 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Other medical conditions or co-morbidity(ies) that, in the opinion of the investigator, would 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 Surgery requiring general anesthesia within the 8 weeks prior to first dose of study drug 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 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the safety and tolerability of ACN00177 in subjects with homocystinuria due to CBS deficiency;Secondary Objective: • Characterize the pharmacokinetic (PK)/pharmacodynamic (PD) relationship of ACN00177 after single and multiple doses following intravenous (IV) and subcutaneous (SC) administration • Evaluate the onset, magnitude of change, and reversibility of changes in plasma total homocysteine (tHcy);Primary end point(s): Incidence of treatment-emergent adverse events (TEAEs) ;Timepoint(s) of evaluation of this end point: 4 weeks and at follow days 29, 36, and 52 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Determine the PK parameters and PK/PD relationship after ACN00177 administration • Determine the proportion of subjects who achieve target plasma tHcy of =50 µM after treatment with ACN00177 • Determine the proportion of subjects who achieve target plasma tHcy of =15 µM after treatment with ACN00177 • Assess the time course of tHcy reduction after ACN00177 administration and reversibility upon follow up post dosing;Timepoint(s) of evaluation of this end point: 4 weeks | — |
Countries
United Kingdom
Contacts
Public ContactPeter Parsonson
Aeglea Biotherapeutics UK Limited
Outcome results
None listed