A study to look at the long-term efficacy and safety of ALN-TTRSC in patients with an inherited condition that causes certain protein molecules to deposit in the heart

• Register: EUCTR
• Last refreshed on: 27 July 2020
• Main ID: EUCTR2015-005333-49-GB
• Date of registration: 04/04/2016
• Prospective Registration: Yes
• Primary sponsor: Alnylam Pharmaceuticals, Inc.
• Public title: A study to look at the long-term efficacy and safety of ALN-TTRSC in patients with an inherited condition that causes certain protein molecules to deposit in the heart
• Scientific title: A Multicenter, Multinational, Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of Revusiran in Patients with Transthyretin-mediated Familial Amyloidotic Cardiomyopathy
• Date of first enrolment: 30/06/2016
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005333-49
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Brazil, Canada, France, Germany, Italy, Mexico, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Trial Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

• Name: Clinical Trial Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Transthyretin (TTR) mediated familial amyloidotic cardiomyopathy (FAC)
MedDRA version: 18.1 Level: PT Classification code 10016202 Term: Familial amyloidosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: Revusiran
Product Code: ALN-TTRSC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Revusiran
Current Sponsor code: ALN-TTRSC
Other descriptive name: ALN-51547
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Secondary Objective: Not Applicable

Primary end point(s): 1. Incidence of adverse events (AEs) and serious adverse events (SAEs)

Main Objective: To assess the safety and efficacy of long-term dosing with revusiran in patients with FAC.

Timepoint(s) of evaluation of this end point: 1. Continuous evaluation over 26 months

Secondary Outcome(s)

Secondary end point(s): 1. Change from baseline in 6-minute walk distance

2. Change from baseline in serum TTR

Timepoint(s) of evaluation of this end point: 1. Every 6 months for 26 months

2. Every 6 months for 26 months

Secondary ID(s)

ALN-TTRSC-006

Source(s) of Monetary Support

Alnylam Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 30/06/2016
Contact: