E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Cystatin C Amyloid Angiopathy (HCCAA) |
Hereditary Cystatin C Amyloid Angiopathy (HCCAA) |
Hereditary Cystatin C Amyloid Angiopathy (HCCAA) |
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E.1.1.1 | Medical condition in easily understood language |
Hereditary disease of the vessels which increases the likelihood and risk of stroke |
Reurrent stroke due to amyloid clogging of brain vessels with dementia |
Endurteknar heilablæðingar og minnisstol |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 safety and tolerability of AT-1 administered orally in adults (ages 18 and over) with HCCAA with or without dementia symptoms • Assess dose-response relationship of AT-1 on HCCAA disease progression, including • Biomarker response from skin biopsies (reduction in cystatin C stain) • Assessment of cognitive status using dementia rating scales
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Evaluate safety and tolerability of AT-1 administered orally in adults (ages 18 and over) with HCCAA with or without dementia symptoms • Assess dose-response relationship of AT-1 on HCCAA disease progression, including • Biomarker response from skin biopsies (reduction in cystatin C stain) • Assessment of cognitive status using dementia rating scales
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E.2.2 | Secondary objectives of the trial |
• Characterize pharmacokinetic parameters of AT-1 when administered orally to adults (ages 18 and over) with HCCAA (n=5) • Assess influence of AT-1 on serum glutathione levels • Assess influence of AT-1 on cystatin C/amyloid dimer formation • Assess excretion of cystatin C in urine and impact of AT-1 treatment
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Characterize pharmacokinetic parameters of AT-1 when administered orally to adults (ages 18 and over) with HCCAA (n=5) • Assess influen |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria 1 Patient is male or female, ages 18 or older, of Icelandic ancestry known to carry the HCCAA mutation L68Q. 2 Patient is judged to be in sufficient medical health to be able to participate in the study. 3 Patient has HCCAA confirmed by mutation status detection of L68Q 4 Patient has been genotyped/sequenced and confirmed to carry the L68Q mutation in the cystatin C gene 5 Patient is willing to have a baseline and follow up skin biopsy every 3 months for up to 9 months. 6 Patient has provided informed consent for participation in trial
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Inclusion Criteria 1 Patient is male or female, ages 18 or older, of Icelandic ancestry known to carry the HCCAA mutation L68Q. 2 Patient is judged to be in sufficient medical health to be able to participate in the study. 3 Patient has HCCAA confirmed by mutation status detection of L68Q 4 Patient has been genotyped/sequenced and confirmed to carry the L68Q mutation in the cystatin C gene 5 Patient is willing to have a baseline and follow up skin biopsy every 3 months for up to 9 months. 6 Patient has provided informed consent for participation in trial
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E.4 | Principal exclusion criteria |
Exclusion Criteria 1. Patient does not have L68Q mutation 2. Patient has clinically significant illness, mental or physical, that, in the opinion of the investigator, might confound the results of the study, pose additional risk to the patient by their participation, or prevent/impede the patient from completing the study. 3. Patient is pregnant or attempting to become pregnant 4. Patient tests positive for illicit drugs (including marijuana) or has history of drug abuse within the last 2 years. 5. Patient consumes excessive amounts of alcoholic beverages. 6. There is any concern by the investigator regarding the patient’s safety, compliance, or suitability with respect to his/her participation in the study.
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Exclusion Criteria 1. Patient does not have L68Q mutation 2. Patient has clinically significant illness, mental or physical, that, in the opinion of the investigator, might confound the results of the study, pose additional risk to the patient by their participation, or prevent/impede the patient from completing the study. 3. Patient is pregnant or attempting to become pregnant 4. Patient tests positive for illicit drugs (including marijuana) or has history of drug abuse within the last 2 years. 5. Patient consumes excessive amounts of alcoholic beverages. 6. There is any concern by the investigator regarding the patient’s safety, compliance, or suitability with respect to his/her participation in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint: • Assessing the biological efficacy, safety and tolerability at AT-1 based on assessment of the stained skin biopsies, AEs and other safety measurements including vital signs, ECG, labs. • The change in skin deposition (reduction in cystatin C/amyloid protein complex stain) following 3, 6, and 9 months treatment with study drug. • The change in cognitive status using dementia rating scales following 3, 6 and 9 months treatment with study drug
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Primary Endpoint: • Assessing the biological efficacy, safety and tolerability at AT-1 based on assessment of the stained skin biopsies, AEs and other safety measurements including vital signs, ECG, labs. • The change in skin deposition (reduction in cystatin C/amyloid protein complex stain) following 3, 6, and 9 months treatment with study drug. • The change in cognitive status using dementia rating scales following 3, 6 and 9 months treatment with study drug
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At month 3, 6, and 9 |
At month 3, 6, and 9 |
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E.5.2 | Secondary end point(s) |
Secondary Endpoint: • Establish pharmacokinetics of AT-1 in a subset of 5 subjects. • GSSG/GSH ratio in blood • Cystatin C/amyloid dimer formation • hCC levels in urine
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Secondary Endpoint: • Establish pharmacokinetics of AT-1 in a subset of 5 subjects. • GSSG/GSH ratio in blood • Cystatin C/amyloid |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3, 6 and 9 months |
3, 6 and 9 months |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.1.1 | First administration to humans | No |
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) | Yes |
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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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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End of study: The study is considered completed after the last patient has completed evaluations, LSLV. |
End of study: The study is considered completed after the last patient has completed evaluations, LSLV. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |