E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin (TTR) Cardiac Amyloidosis |
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E.1.1.1 | Medical condition in easily understood language |
ATTR is a hereditary disease caused by protein aggregates in the heart and the nervous system. It leads to heart dysfunction, damages to the nerves, and gastrointestinal and bladder dysfunctions |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10010331 |
E.1.2 | Term | Congenital, familial and genetic disorders |
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 |
To evaluate the safety and tolerability of multiple doses of ALN-TTRSC |
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E.2.2 | Secondary objectives of the trial |
To assess the pharmacodynamic (PD) effect of multiple dose of ALN-TTRSC on serum levels of transthyretin (TTR)
To characterize the pharmacokinetics (PK) of multiple doses of ALN-TTRSC
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males or females 18 to 80 years of age, inclusive;
Biopsy-proven TTR cardiac amyloidosis
NYHA Class ≤3
Stable congestive heart failure status and stable clinical treatment
Able to walk ≥150 meters
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E.4 | Principal exclusion criteria |
Uncontrolled hypertension;
Uncontrolled ischemic heart disease;
Uncontrolled clinically significant cardiac arrhythmia;
Untreated hypo- or hyperthyroidism
Prior major organ transplant;
Known or suspected systemic bacterial, viral, parasitic, or fungal infection;
Seropositive for hepatitis B virus (HBV), hepatitis C virus (HCV) or known to be human immunodeficiency virus (HIV) positive;
Received an investigational agent other than tafamidis, diflunisal, doxycycline or tauroursodeoxycholic acid, or an investigational device within 30 days prior to first dose of study drug;
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability of multiple doses of ALN-TTRSC, including:
•assessment of adverse events (AEs),
•vital signs (blood pressure, pulse rate, oral body temperature and respiratory rate),
•clinical laboratory safety tests (hematology, serum chemistry, thyroid function, coagulation, and urinalysis)
•12-lead ECG
•physical examinations
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
•The review of AEs will be done at each visit through D63.
•The other assessments will be carried out at specific timepoints between screening and D90, as described in the study schedule.
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E.5.2 | Secondary end point(s) |
•To assess the PD effect of multiple doses of ALN-TTRSC
•To assess the PK profile of multiple doses of ALN-TTRSC
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•An assessment of the concentrations of serum TTR, will be determined at specified time points between screening and D90 , as described in the study schedule.
•An assessment of the PK of ALN-TTRSC will be determined at specified time points between D0 and D90, as described in the study schedule.
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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 | 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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |