E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Homocystinuria Due to Cystathionine β-Synthase (CBS) Deficiency |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020365 |
E.1.2 | Term | Homocystinuria |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the safety and tolerability of ACN00177 in subjects with homocystinuria due to CBS deficiency |
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E.2.2 | Secondary objectives of the trial |
• 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) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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)
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of treatment-emergent adverse events (TEAEs)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks and at follow days 29, 36, and 52 days |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 15 |