E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin mediated amyloidosis (ATTR) |
|
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. |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007509 |
E.1.2 | Term | Cardiac amyloidosis |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019889 |
E.1.2 | Term | Hereditary neuropathic amyloidosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 long-term dosing with ALN-TTR02. |
|
E.2.2 | Secondary objectives of the trial |
To assess the PD effect associated with long-term dosing of ALN-TTR02 on serum TTR.
To assess changes from baseline in:
• Neurologic impairment, quality of life and disability, motor function impacting activities of daily living, and nutritional status. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Previously received and tolerated ALN-TTR02 in Study ALN-TTR02-002.
2. Adequate Karnofsky performance status, liver function, and renal function.
Additional inclusion criteria are utilized to assess entry in PK subgroup and for the cardiac subgroup.
|
|
E.4 | Principal exclusion criteria |
1. Pregnant or nursing.
2. Has had a liver transplant.
3. Has a New York Heart Association heart failure classification >2.
4. Has unstable angina.
5. Has uncontrolled clinically significant cardiac arrhythmia.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the safety and tolerability of long-term dosing with ALN-TTR02:
•assessment of adverse events (AEs),
•12 lead electrocardiograms (ECGs),
•vital signs (blood pressure, pulse rate, oral body temperature and respiratory rate),
•clinical laboratory safety tests (hematology, serum chemistry, thyroid function, coagulation, and urinalysis),
•ophthalmology examinations, and
•physical examinations. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The review of AEs will be done at each visit from Day 0 through through 56 days post last dose. The other assessments will be carried out at specific timepoints between screening and 56 days post last dose, as descibed in the study schedule. |
|
E.5.2 | Secondary end point(s) |
To assess the PD effect associated with long-term dosing of ALN-TTR02 on serum TTR.
To assess changes from baseline in:
• Neurologic impairment, quality of life and disability, motor function impacting activities of daily living, and nutritional status. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
An assessment of the concentrations of serum TTR, RBP, and Vitamin A will be determined at specified time points between screening and 56 days post last dose, as described in the study schedule.
Other assessments of neurologic impairment and QOL will be performed approximately every six months for approximately two years. |
|
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 | Yes |
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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Brazil |
France |
Germany |
Portugal |
Spain |
Sweden |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |