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A Extension Study to Evaluate Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Cardiac Amyloidosis

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ClinicalTrials.gov Identifier: NCT02292186
Recruitment Status : Completed
First Posted : November 17, 2014
Results First Posted : June 15, 2018
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition TTR-mediated Amyloidosis
Intervention Drug: Revusiran (ALN-TTRSC)
Enrollment 25
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description All patients who received at least 1 dose of revusiran
Period Title: Overall Study
Started 25
Completed 7
Not Completed 18
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description All patients who received at least 1 dose of revusiran
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
All patients who received at least 1 dose of revusiran
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants
68.8  (6.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
3
  12.0%
Male
22
  88.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
20
  80.0%
Unknown or Not Reported
5
  20.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  16.0%
White
21
  84.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Safety and Tolerability Results of Long-term Dosing With ALN-TTRSC (Revusiran) Transthyretin (TTR) Cardiac Amyloidosis Patients.
Hide Description The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study [drug] discontinuation.
Time Frame Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description:
All patients who received at least 1 dose of revusiran
Overall Number of Participants Analyzed 25
Measure Type: Count of Participants
Unit of Measure: Participants
At least 1 AE (adverse event)
25
 100.0%
At least 1 SAE (serious adverse event)
22
  88.0%
Study discontinuation for any reason
18
  72.0%
2.Primary Outcome
Title Serum TTR Levels
Hide Description Pharmacodynamic (PD) effect of long-term dosing of ALN-TTRSC on serum levels of TTR
Time Frame Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
Hide Outcome Measure Data
Hide Analysis Population Description
Long term samples not collected due to study termination; no data to analyze
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description:
All patients who received at least 1 dose of revusiran
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Mortality
Hide Description Total number of deaths in the study and total number of deaths adjudicated as being related to cardiovascular causes. Deaths were adjudicated by an independent adjudication committee as cardiovascular (CV) or non-CV events.
Time Frame Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description:
All patients who received at least 1 dose of revusiran
Overall Number of Participants Analyzed 25
Measure Type: Count of Participants
Unit of Measure: Participants
Total deaths
8
  32.0%
Total CV mortality events
6
  24.0%
4.Secondary Outcome
Title Clinical Effects of Long-term Dosing of ALN-TTRSC on Hospitalization
Hide Description Hospitalization events were adjudicated by an independent committee as cardiovascular (CV) or non-CV events
Time Frame Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description:
All patients who received at least 1 dose of revusiran
Overall Number of Participants Analyzed 25
Measure Type: Count of Participants
Unit of Measure: Participants
At least 1 hospitalization event on study
17
  68.0%
At least 1 CV hospitalization event
15
  60.0%
5.Secondary Outcome
Title 6-minute Walk Test Performance
Hide Description Distance in meters walked in 6 minutes
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed differs from baseline to 6 and 12 months due to study discontinuations
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description:
All patients who received at least 1 dose of revusiran
Overall Number of Participants Analyzed 25
Mean (Standard Deviation)
Unit of Measure: meters
Change from baseline at Month 6 Number Analyzed 19 participants
-20.6  (46.1)
Change from baseline at Month 12 Number Analyzed 15 participants
-104.6  (88.6)
Time Frame All AEs that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Mean duration of collection was 16 months.
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
 
Arm/Group Title Revusiran (ALN-TTRSC)
Hide Arm/Group Description All patients who received at least 1 dose of revusiran
All-Cause Mortality
Revusiran (ALN-TTRSC)
Affected / at Risk (%)
Total   8/25 (32.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Revusiran (ALN-TTRSC)
Affected / at Risk (%) # Events
Total   22/25 (88.00%)    
Cardiac disorders   
Cardiac failure  1  6/25 (24.00%)  6
Cardiac failure congestive  1  3/25 (12.00%)  3
Atrial fibrillation  1  2/25 (8.00%)  2
Cardiac arrest  1  2/25 (8.00%)  2
Cardiac failure acute  1  2/25 (8.00%)  2
Cardiogenic shock  1  2/25 (8.00%)  2
Bradycardia  1  1/25 (4.00%)  1
Left ventricular dysfunction  1  1/25 (4.00%)  1
Atrial flutter  1  1/25 (4.00%)  1
Right ventricular failure  1  1/25 (4.00%)  1
Gastrointestinal disorders   
Constipation  1  2/25 (8.00%)  2
Rectal haemorrhage  1  1/25 (4.00%)  1
Large intestinal ulcer  1  1/25 (4.00%)  1
General disorders   
Generalised oedema  1  1/25 (4.00%)  3
Fatigue  1  1/25 (4.00%)  1
Asthenia  1  1/25 (4.00%)  1
Immune system disorders   
Amyloidosis  1  1/25 (4.00%)  1
Infections and infestations   
Pneumonia  1  3/25 (12.00%)  4
Lower respiratory tract infection  1  2/25 (8.00%)  2
Sepsis  1  2/25 (8.00%)  2
Cellulitis  1  1/25 (4.00%)  1
Injury, poisoning and procedural complications   
Fall  1  1/25 (4.00%)  1
Vasoplegia syndrome  1  1/25 (4.00%)  1
Investigations   
Blood lactic acid increased  1  3/25 (12.00%)  3
Electrocardiogram QRS complex prolonged  1  1/25 (4.00%)  1
Metabolism and nutrition disorders   
Fluid overload  1  2/25 (8.00%)  2
Lactic acidosis  1  1/25 (4.00%)  1
Dehydration  1  1/25 (4.00%)  1
Decreased appetite  1  1/25 (4.00%)  1
Musculoskeletal and connective tissue disorders   
Myopathy  1  1/25 (4.00%)  1
Musculoskeletal chest pain  1  1/25 (4.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Colon cancer  1  1/25 (4.00%)  1
Nervous system disorders   
Neuropathy peripheral  1  7/25 (28.00%)  8
Cerebrovascular accident  1  2/25 (8.00%)  2
Dizziness  1  2/25 (8.00%)  2
Neuralgia  1  2/25 (8.00%)  2
Syncope  1  1/25 (4.00%)  1
Depressed level of consciousness  1  1/25 (4.00%)  1
Psychiatric disorders   
Completed suicide  1  1/25 (4.00%)  1
Renal and urinary disorders   
Renal impairment  1  3/25 (12.00%)  3
Renal failure acute  1  2/25 (8.00%)  2
Obstructive uropathy  1  1/25 (4.00%)  1
Renal failure chronic  1  1/25 (4.00%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  3/25 (12.00%)  3
Haemoptysis  1  1/25 (4.00%)  1
Pleuritic pain  1  1/25 (4.00%)  1
Vascular disorders   
Hypotension  1  6/25 (24.00%)  6
1
Term from vocabulary, MedDRA18.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Revusiran (ALN-TTRSC)
Affected / at Risk (%) # Events
Total   25/25 (100.00%)    
Cardiac disorders   
Atrial fibrillation  1  7/25 (28.00%)  7
Cardiac failure  1  4/25 (16.00%)  4
Pericardial effusion  1  2/25 (8.00%)  2
Ear and labyrinth disorders   
Vertigo  1  2/25 (8.00%)  2
Gastrointestinal disorders   
Constipation  1  9/25 (36.00%)  10
Diarrhoea  1  6/25 (24.00%)  6
Nausea  1  5/25 (20.00%)  5
Abdominal distension  1  2/25 (8.00%)  3
Abdominal discomfort  1  3/25 (12.00%)  3
Vomiting  1  2/25 (8.00%)  3
General disorders   
Oedema peripheral  1  9/25 (36.00%)  13
Fatigue  1  8/25 (32.00%)  8
Injection site erythema  1  8/25 (32.00%)  41
Injection site pruritus  1  6/25 (24.00%)  29
Injection site pain  1  5/25 (20.00%)  14
Injection site swelling  1  4/25 (16.00%)  16
Injection site discoloration  1  2/25 (8.00%)  2
Pyrexia  1  2/25 (8.00%)  2
Injection site inflammation  1  2/25 (8.00%)  3
Injection site haematoma  1  2/25 (8.00%)  2
Infections and infestations   
Urinary tract infection  1  7/25 (28.00%)  8
Lower respiratory tract infection  1  3/25 (12.00%)  5
Pneumonia  1  2/25 (8.00%)  2
Sinusitis  1  2/25 (8.00%)  2
Tooth infection  1  2/25 (8.00%)  2
Bronchitis  1  3/25 (12.00%)  3
Onychomycosis  1  2/25 (8.00%)  2
Injury, poisoning and procedural complications   
Fall  1  10/25 (40.00%)  11
Contusion  1  4/25 (16.00%)  4
Excoriation  1  2/25 (8.00%)  2
Laceration  1  2/25 (8.00%)  2
Traumatic haematoma  1  2/25 (8.00%)  2
Investigations   
Weight decreased  1  7/25 (28.00%)  9
Blood lactic acid increased  1  2/25 (8.00%)  2
International normalized ratio increased  1  5/25 (20.00%)  8
Liver function test abnormal  1  4/25 (16.00%)  4
Vitamin A decreased  1  4/25 (16.00%)  4
Gamma-glutamyltransferase increased  1  2/25 (8.00%)  2
Blood creatinine increased  1  2/25 (8.00%)  2
Blood urea increased  1  2/25 (8.00%)  2
Metabolism and nutrition disorders   
Decreased appetite  1  4/25 (16.00%)  4
Fluid overload  1  3/25 (12.00%)  3
Hyperglycemia  1  2/25 (8.00%)  2
Hyponatremia  1  3/25 (12.00%)  3
Dehydration  1  2/25 (8.00%)  2
Hyperkalemia  1  2/25 (8.00%)  2
Gout  1  2/25 (8.00%)  2
Musculoskeletal and connective tissue disorders   
Muscle spasms  1  6/25 (24.00%)  7
Pain in extremity  1  3/25 (12.00%)  4
Joint swelling  1  3/25 (12.00%)  3
Back pain  1  2/25 (8.00%)  2
Arthralgia  1  2/25 (8.00%)  2
Carpal tunnel syndrome  1  2/25 (8.00%)  2
Intervertebral disk degeneration  1  2/25 (8.00%)  2
Nervous system disorders   
Dizziness  1  10/25 (40.00%)  14
Neuropathy peripheral  1  9/25 (36.00%)  12
Headache  1  3/25 (12.00%)  3
Tremor  1  2/25 (8.00%)  2
Dysgeusia  1  2/25 (8.00%)  2
Psychiatric disorders   
Depression  1  3/25 (12.00%)  3
Insomnia  1  2/25 (8.00%)  2
Renal and urinary disorders   
Renal failure acute  1  4/25 (16.00%)  5
Urinary retention  1  2/25 (8.00%)  2
Reproductive system and breast disorders   
Erectile dysfunction  1  2/25 (8.00%)  2
Benign prostatic hyperplasia  1  2/25 (8.00%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  12/25 (48.00%)  17
Dyspnoea  1  7/25 (28.00%)  10
Pleural effusion  1  5/25 (20.00%)  7
Nasal congestion  1  2/25 (8.00%)  2
Rales  1  2/25 (8.00%)  2
Productive cough  1  2/25 (8.00%)  2
Skin and subcutaneous tissue disorders   
Rash  1  2/25 (8.00%)  4
Increased tendency to bruise  1  2/25 (8.00%)  2
Pruritus  1  3/25 (12.00%)  3
Decubitus ulcer  1  2/25 (8.00%)  2
Vascular disorders   
Hypotension  1  4/25 (16.00%)  5
Orthostatic hypotension  1  4/25 (16.00%)  6
Flushing  1  2/25 (8.00%)  8
1
Term from vocabulary, MedDRA18.0
Indicates events were collected by systematic assessment
Safety and efficacy data are difficult to interpret due to the limited numbers of patients completing the study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Alnylam Pharmaceuticals Inc
Phone: 866-330-0326
Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02292186     History of Changes
Other Study ID Numbers: ALN-TTRSC-003
First Submitted: November 10, 2014
First Posted: November 17, 2014
Results First Submitted: February 22, 2018
Results First Posted: June 15, 2018
Last Update Posted: July 18, 2018