A Phase 1/2 Study of ACN00177 in Subjects With Homocystinuria Due to Cystathionine ß-Synthase (CBS) Deficiency
- Conditions
- Homocystinuria Due to Cystathionine ß-Synthase (CBS) DeficiencyMedDRA version: 20.0Level: PTClassification code 10020365Term: HomocystinuriaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2019-004791-19-GB
- Lead Sponsor
- Aeglea Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 25
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
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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>•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)<br><br>;Timepoint(s) of evaluation of this end point: 4 weeks and at follow days 29, 36, and 52 days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Determine the PK parameters and PK/PD relationship after ACN00177 administration<br>•Determine the proportion of subjects who achieve target plasma tHcy of =50 µM after treatment with ACN00177<br>•Determine the proportion of subjects who achieve target plasma tHcy of =15 µM after treatment with ACN00177<br>•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