Clinical Trial Results:
A Phase 2, Open-Label Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Exploratory Clinical Activity of ALN-TTRSC in Patients with Transthyretin (TTR) Cardiac Amyloidosis
Summary
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EudraCT number |
2013-002856-33 |
Trial protocol |
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Global end of trial date |
05 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Apr 2016
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First version publication date |
09 Apr 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ALN-TTRSC-002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01981837 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Alnylam Pharmaceuticals, Inc.
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Sponsor organisation address |
300 Third Street, Cambridge, MA, United States, 02142
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Public contact |
Investor Relations & Corporate Communication, Alnylam Pharmaceuticals, Inc., investors@alnylam.com
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Scientific contact |
Senior Vice President, Clinical Development, Alnylam Pharmaceuticals, Inc., clinicaltrials@alnylam.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Jun 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Jan 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jan 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety and tolerability of multiple doses of ALN-TTRSC (revusiran) in patients with ATTR cardiac amyloidosis.
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Protection of trial subjects |
A Safety Review Committee (SRC) was in place for this study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Jan 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 10
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Country: Number of subjects enrolled |
United States: 16
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Worldwide total number of subjects |
26
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
19
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||
Pre-assignment
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Screening details |
A total of 26 patients who met all inclusion criteria and none of the exclusion criteria were enrolled. | |||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ALN-TTRSC (revusiran) 5.0 mg/kg | |||||||||
Arm description |
Patients received 5.0 mg/kg of ALN-TTRSC (revusiran) for a total of 10 doses | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Revusiran
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Investigational medicinal product code |
ALN-TTRSC
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
5.0 mg/kg of ALN-TTRSC (revusiran) for a total of 10 doses. Patients received a daily dose of ALN-TTRSC (revusiran) over 5 consecutive days (Days 0, 1, 2, 3, and 4) and then they received once weekly doses of ALN-TTRSC (revusiran) for 5 weeks (Days 7, 14, 21, 28, and 35).
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Arm title
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ALN-TTRSC (revusiran) 7.5 mg/kg | |||||||||
Arm description |
Patients received 7.5 mg/kg of ALN-TTRSC (revusiran) for a total of 10 doses | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Revusiran
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Investigational medicinal product code |
ALN-TTRSC
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
7.5 mg/kg of ALN-TTRSC (revusiran) for a total of 10 doses. Patients received a daily dose of ALN-TTRSC (revusiran) over 5 consecutive days (Days 0, 1, 2, 3, and 4) and then they received once weekly doses of ALN-TTRSC (revusiran) for 5 weeks (Days 7, 14, 21, 28, and 35).
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ALN-TTRSC (revusiran) 5.0 mg/kg
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Reporting group description |
Patients received 5.0 mg/kg of ALN-TTRSC (revusiran) for a total of 10 doses | ||
Reporting group title |
ALN-TTRSC (revusiran) 7.5 mg/kg
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Reporting group description |
Patients received 7.5 mg/kg of ALN-TTRSC (revusiran) for a total of 10 doses |
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End point title |
Safety and tolerability of multiple doses of ALN-TTRSC (revusiran) in patients with ATTR cardiac amyloidosis [1] | ||||||||||||||||||
End point description |
The number of patients experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation (due to any reason)
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End point type |
Primary
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End point timeframe |
Up to 90 days post first dose
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential analyses were conducted as the primary endpoint was safety and tolerability. Analyses were descriptive in nature. |
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No statistical analyses for this end point |
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End point title |
Pharmacokinetic parameters of ALN-TTRSC (revusiran): AUC | ||||||||||||||||||||||||||||||
End point description |
Partial area under the plasma concentration-time curve from time 0 to 24 hours (AUC 0-24) and area under the curve from time 0 to the last quantifiable concentration (AUC 0-last) of ALN-TTRSC (revusiran)
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End point type |
Secondary
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End point timeframe |
Up to 90 days post first dose
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No statistical analyses for this end point |
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End point title |
Serum transthyretin (TTR) protein | ||||||||||||||||||
End point description |
Percent lowering of TTR relative to pretreatment/baseline levels
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End point type |
Secondary
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End point timeframe |
Up to 90 days post first dose
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No statistical analyses for this end point |
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End point title |
Pharmacokinetic parameters of ALN-TTRSC (revusiran): Cmax | |||||||||||||||||||||
End point description |
Maximum observed plasma concentration (Cmax) of ALN-TTRSC (revusiran)
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End point type |
Secondary
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End point timeframe |
Up to 90 days post first dose
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No statistical analyses for this end point |
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End point title |
Pharmacokinetic parameters of ALN-TTRSC (revusiran): tmax | |||||||||||||||||||||
End point description |
Time of maximum observed plasma concentration (tmax) of ALN-TTRSC (revusiran)
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End point type |
Secondary
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End point timeframe |
Up to 90 days
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No statistical analyses for this end point |
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End point title |
Pharmacokinetic parameters of ALN-TTRSC (revusiran): CLss/F | ||||||||||||||||||
End point description |
Systemic clearance (CLss/F) of ALN-TTRSC (revusiran)
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End point type |
Secondary
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End point timeframe |
Up to 90 days post first dose
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
The Investigator reported all AEs that occurred after the first dose of study drug through the Day 63 or Early Termination visit regardless of their relationship to study drug or clinical significance.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Sep 2013 |
Protocol Amendment 1
• The method of acceptable contraception for study participants was revised to reflect MHRA guidelines
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16 Oct 2013 |
Protocol Amendment 2
• Increased patient numbers from 12 to 15
• Study drug dose decreased from 7.5 mg/kg to 5.0 mg/kg |
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21 Jan 2014 |
Protocol Amendment 3
• Changes to timings of pharmacokinetic blood draws
• Measurement of vitamin A serum levels added to the Schedule of Assessments for the Day 35 visit |
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20 May 2014 |
Protocol Amendment 4
• The number of patients was increased to approximately 25 patients
• Inclusion Criterion #2 was changed to include only cardiac amyloidosis patients with a TTR mutation
• Exclusion Criterion #5 was modified to exclude patients with vitamin A levels consistent with vitamin A deficiency (ie, <20 µg/dL) |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |