E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin (TTR) mediated familial amyloidotic cardiomyopathy (FAC) |
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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, damage to the nerves and gastrointestinal and bladder dysfunction. |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016202 |
E.1.2 | Term | Familial amyloidosis |
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 assess the safety and efficacy of long-term dosing with revusiran in patients with FAC. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completed and, in the opinion of the Investigator, tolerated study drug dosing in Study ALN-TTRSC-004 (ie, completed the Month 18 visit)
2. Women of child-bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must use 1 highly effective method of contraception in combination with a barrier method throughout study participation and for 28 days after last dose of study drug
3. Male patients with partners of child-bearing potential must agree to use a condom, accompanied with spermicidal foam, gel, film, cream, or suppository,
except in countries where spermicide is not available for use in combination with a condom, throughout study participation and for 28 days after the last dose of study drug; males must also abstain from sperm donation after the first dose of study drug through study participation and for 28 days after the last dose of study drug
4. Willing and able to comply with the protocol-required visit schedule and requirements and provide informed consent or have a legal guardian who can provide informed consent |
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E.4 | Principal exclusion criteria |
1. AST and ALT >2 × ULN, or total bilirubin >2 mg/dL (34.2 μmol/L), unless elevation in total bilirubin is due to Gilbert's syndrome. If a patient does not meet this exclusion criterion but does not meet dose holding criteria for this study, then the patient may be
enrolled after consultation with the Medical Monitor.
2. eGFR <15 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease [MDRD] formula)
3. Is currently taking tafamidis, diflunisal, doxycycline, or tauroursodeoxycholic acid; if
previously on any of these agents, must have completed a 14-day wash-out prior to start of study drug administration in this study
4. Received an investigational agent or device, other than revusiran or placebo in ALN-TTRSC-004, within 28 days of anticipated study drug administration or 5 half-lives of the investigational drug, whichever is longer
5. History of allergic reaction to an oligonucleotide or GalNAc
6. Any significant change in the patient’s medical status or comorbidities that, in the opinion of the Investigator, would interfere with study compliance or data interpretation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence of adverse events (AEs) and serious adverse events (SAEs) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Continuous evaluation over 26 months |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in 6-minute walk distance
2. Change from baseline in serum TTR |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Every 6 months for 26 months
2. Every 6 months for 26 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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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 | 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
| 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Belgium |
Brazil |
Canada |
France |
Germany |
Italy |
Mexico |
Spain |
Sweden |
United States |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |