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 | 19.1 |
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 | 19.1 |
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 determine the efficacy of ALN-TTR02 |
|
E.2.2 | Secondary objectives of the trial |
To determine the effect of ALN-TTR02 on various clinical parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female of 18 to 85 years of age (inclusive);
• Have a diagnosis of FAP
• Meet Neuropathy Impairment Score requirements and Karnofsky performance status requirements
• Have adequate complete blood counts and liver function tests
• Have adequate cardiac function
• No active infection with hepatitis B or hepatitis C |
|
E.4 | Principal exclusion criteria |
• Had a prior liver transplant or is planned to undergo liver transplant during the study period;
• Has untreated hypo- or hyperthyroidism;
• Has known human immunodeficiency virus (HIV) infection;
• Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated;
• Recently received an investigational agent or device
• Is currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The difference between the ALN TTR02 and placebo groups in the change from baseline of modified Neuropathy Impairment Score+7 (mNIS+7) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The difference between the ALN TTR02 and placebo groups in the change from baseline of modified NIS+7 (mNIS+7) at 18 months |
|
E.5.2 | Secondary end point(s) |
The difference between ALN-TTR02 and placebo in the change from baseline in the following measurements:
• Quality of Life
• Modified Body Mass Index
• Autonomic function
• Muscle weakness as assessed by walking test
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The difference between ALN-TTR02 and placebo in the change from baseline in the various clinical parameters at 18 months |
|
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Argentina |
Brazil |
Bulgaria |
France |
Germany |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
Portugal |
Spain |
Sweden |
Taiwan |
Turkey |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |