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The Study of ALN-TTR02 (Patisiran) for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Who Have Already Been Treated With ALN-TTR02 (Patisiran)

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ClinicalTrials.gov Identifier: NCT01961921
Recruitment Status : Completed
First Posted : October 14, 2013
Results First Posted : October 30, 2018
Last Update Posted : December 4, 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: ALN-TTR02 (patisiran) administered by intravenous (IV) infusion
Enrollment 27
Recruitment Details A total of 27 subjects were enrolled.
Pre-assignment Details  
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Period Title: Overall Study
Started 27
Completed 25
Not Completed 2
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Baseline Participants 27
Hide Baseline Analysis Population Description
All patients who received at least one dose of ALN-TTR02 (patisiran)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
<=18 years
0
   0.0%
Between 18 and 65 years
14
  51.9%
>=65 years
13
  48.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants
57.9  (15.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
Female
9
  33.3%
Male
18
  66.7%
Familial Amyloidotic Polyneuropathy (FAP) Stage  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
FAP Stage I: Unimpaired ambulation
24
  88.9%
FAP Stage II: Assistance with ambulation required
3
  11.1%
FAP Stage III: Wheelchair-bound or bedridden
0
   0.0%
1.Primary Outcome
Title The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation
Hide Description An AE is any untoward medical occurrence in a patient or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Time Frame From Baseline up to 56 days post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: All participants who received at least one dose of study drug.
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description:
Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: participants
At least 1 Treatment Emergent Adverse Event (TAE) 26
At least 1 Serious Adverse Event (SAE) 7
Study Drug Discontinuation for any reason 2
2.Secondary Outcome
Title Percentage Change From Baseline in Serum TTR Levels
Hide Description TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method.
Time Frame From Baseline up to 56 days post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All participants who were enrolled were included in the full analysis set.
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description:
Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Participants Analyzed 27
Mean (Standard Error)
Unit of Measure: Percent Change
Individual TTR % change -82.06  (1.33)
Individual Predose TTR % change -79.73  (1.45)
Individual Max TTR % change -92.54  (0.67)
3.Secondary Outcome
Title Change From Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7)
Hide Description The mNIS+7 assessment is a composite measure of neurologic impairment that provides a comprehensive measure of large and small fiber function that encompasses the totality of the motor, sensory, and autonomic deficits seen in hereditary transthyretin-mediated amyloidosis (hATTR) patients with polyneuropathy. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All participants who were enrolled were included in the full analysis set. The number of participants analyzed is the number for whom evaluable data were available.
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description:
Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: score on a scale
Baseline Number Analyzed 27 participants
50.5
(2.00 to 122.50)
Change from Baseline at Month 24 Number Analyzed 26 participants
-7.00
(-34.63 to 15.38)
4.Secondary Outcome
Title Change From Baseline in Quality of Life and Disability as Assessed by the EuroQoL (Quality of Life)-5 Dimensions (EQ-5D), EuroQoL Visual Analog Scale (EQ-VAS) Questionnaires and Rasch-built Overall Disability Scale (R-ODS)
Hide Description The overall EQ-5D is measured on a scale from 0 to 1, with 0 being worst and 1 best. The EQ-VAS is measured on a scale of 0-100, with 0 being the worst and 100 the best. The R-ODS captures activity and social participation limitations in patients. The R-ODS score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations).
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All participants who were enrolled were included in the full analysis set. The number of participants analyzed is the number for whom evaluable data were available.
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description:
Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: Score on a scale
EQ-5D Score at Baseline Number Analyzed 27 participants
0.76
(0.31 to 1.00)
EQ-5D Score: Change from Baseline at Month 24 Number Analyzed 26 participants
0.00
(-0.22 to 0.17)
EQ-VAS Score at Baseline Number Analyzed 27 participants
70.0
(30 to 98)
EQ-VAS Score: Change from Baseline at Month 24 Number Analyzed 26 participants
0.0
(-25 to 30)
R-ODS Score at Baseline Number Analyzed 26 participants
38.5
(15 to 48)
R-ODS Score: Change from Baseline at Month 24 Number Analyzed 25 participants
-1.0
(-14 to 8)
5.Secondary Outcome
Title Change in Gait Speed With 10-meter Walk Test
Hide Description The 10-meter walk test measures the time (in seconds) that it takes a patient to walk 10 meters.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All participants who were enrolled were included in the full analysis set. The number of participants analyzed is the number for whom evaluable data were available.
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description:
Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Participants Analyzed 22
Median (Full Range)
Unit of Measure: m/sec
Baseline Number Analyzed 22 participants
1.13
(0.4 to 2.2)
Change from Baseline at Month 24 Number Analyzed 21 participants
0.09
(-0.4 to 0.3)
6.Secondary Outcome
Title Mean Change From Baseline in Hand Grip Strength
Hide Description The mean (SEM) hand grip strength change from baseline at 24 months between patients who used patisiran with or without a concomitant TTR stabilizer.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All participants who were enrolled were included in the full analysis set. The number of participants analyzed is the number for whom evaluable data were available.
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description:
Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: kg
Baseline Number Analyzed 27 participants
23.88
(3.2 to 49.3)
Change from Baseline at Month 24 Number Analyzed 26 participants
1.54
(-17.2 to 22.7)
7.Secondary Outcome
Title Change From Baseline in Nutritional Status (Modified Body Mass Index, mBMI)
Hide Description Nutritional status of patients was evaluated using the mBMI, calculated as BMI (kg/m^2) multiplied by albumin (g/L). An increase from baseline in mBMI suggests improvement, and a decrease from baseline suggests worsening.
Time Frame Baseline, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All participants who were enrolled were included in the full analysis set. The number of participants analyzed is the number for whom evaluable data were available.
Arm/Group Title ALN-TTR02 (Patisiran)
Hide Arm/Group Description:
Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: kg/m^2 x albumin g/L
Baseline Number Analyzed 27 participants
1049.09
(728.6 to 1379.6)
Change from Baseline at Month 24 Number Analyzed 22 participants
-39.85
(-368.8 to 258.9)
Time Frame The investigators reported all AEs that occurred after the start of study drug administration on Day 0 (Baseline) through 21 or 56 days after the last dose of study drug administration (depending on enrollment into the open-label global extension study).
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 Safety Population
Hide Arm/Group Description All patients who received at least one dose of ALN-TTR02 (patisiran)
All-Cause Mortality
Safety Population
Affected / at Risk (%)
Total   2/27 (7.41%) 
Show Serious Adverse Events Hide Serious Adverse Events
Safety Population
Affected / at Risk (%)
Total   7/27 (25.93%) 
Cardiac disorders   
Cardiac amyloidosis  1  1/27 (3.70%) 
Myocardial infarction  1  1/27 (3.70%) 
Infections and infestations   
Abscess limb  1  1/27 (3.70%) 
Osteomyelitis  1  1/27 (3.70%) 
Urinary tract infection  1  1/27 (3.70%) 
Injury, poisoning and procedural complications   
Ankle fracture  1  1/27 (3.70%) 
Femur fracture  1  1/27 (3.70%) 
Foot fracture  1  1/27 (3.70%) 
Ligament rupture  1  1/27 (3.70%) 
Thermal burn  1  1/27 (3.70%) 
Tibia fracture  1  1/27 (3.70%) 
Metabolism and nutrition disorders   
Dehydration  1  1/27 (3.70%) 
Musculoskeletal and connective tissue disorders   
Osteonecrosis  1  2/27 (7.41%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Oesophageal carcinoma  1  1/27 (3.70%) 
Renal and urinary disorders   
Acute prerenal failure  1  1/27 (3.70%) 
Surgical and medical procedures   
Arthrodesis  1  1/27 (3.70%) 
Vascular disorders   
Venous thrombosis limb  1  1/27 (3.70%) 
1
Term from vocabulary, MedDRA (18.0)
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%
Safety Population
Affected / at Risk (%)
Total   26/27 (96.30%) 
Blood and lymphatic system disorders   
Anaemia  1  3/27 (11.11%) 
Eye disorders   
Cataract  1  3/27 (11.11%) 
Macular degeneration  1  3/27 (11.11%) 
Macular fibrosis  1  2/27 (7.41%) 
Visual acuity reduced  1  2/27 (7.41%) 
Gastrointestinal disorders   
Diarrhoea  1  6/27 (22.22%) 
Vomiting  1  6/27 (22.22%) 
Nausea  1  5/27 (18.52%) 
Abdominal pain  1  2/27 (7.41%) 
Dyspepsia  1  2/27 (7.41%) 
General disorders   
Pyrexia  1  4/27 (14.81%) 
Infusion site extravasation  1  3/27 (11.11%) 
Oedema peripheral  1  3/27 (11.11%) 
Early satiety  1  2/27 (7.41%) 
Fatigue  1  2/27 (7.41%) 
Gait disturbance  1  2/27 (7.41%) 
Infusion site erythema  1  2/27 (7.41%) 
Pain  1  2/27 (7.41%) 
Immune system disorders   
Infusion related reaction  1  6/27 (22.22%) 
Infections and infestations   
Nasopharyngitis  1  6/27 (22.22%) 
Urinary tract infection  1  5/27 (18.52%) 
Bronchitis  1  3/27 (11.11%) 
Cellulitis  1  2/27 (7.41%) 
Influenza  1  2/27 (7.41%) 
Sinusitis  1  2/27 (7.41%) 
Upper respiratory tract infection  1  2/27 (7.41%) 
Wound infection  1  2/27 (7.41%) 
Injury, poisoning and procedural complications   
Wound  1  6/27 (22.22%) 
Fall  1  2/27 (7.41%) 
Foot fracture  1  2/27 (7.41%) 
Investigations   
Blood thyroid stimulating hormone decreased  1  2/27 (7.41%) 
Weight decreased  1  2/27 (7.41%) 
Metabolism and nutrition disorders   
Hypocalcaemia  1  2/27 (7.41%) 
Musculoskeletal and connective tissue disorders   
Musculoskeletal pain  1  3/27 (11.11%) 
Osteoporosis  1  3/27 (11.11%) 
Arthralgia  1  2/27 (7.41%) 
Back pain  1  2/27 (7.41%) 
Osteoarthritis  1  2/27 (7.41%) 
Osteopenia  1  2/27 (7.41%) 
Pain in extremity  1  2/27 (7.41%) 
Nervous system disorders   
Neuralgia  1  4/27 (14.81%) 
Headache  1  2/27 (7.41%) 
Hypoaesthesia  1  2/27 (7.41%) 
Visual field defect  1  2/27 (7.41%) 
Psychiatric disorders   
Insomnia  1  4/27 (14.81%) 
Depression  1  2/27 (7.41%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/27 (7.41%) 
Skin and subcutaneous tissue disorders   
Erythema  1  2/27 (7.41%) 
Skin ulcer  1  2/27 (7.41%) 
Vascular disorders   
Flushing  1  7/27 (25.93%) 
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
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: 1-877-256-9526
Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01961921     History of Changes
Other Study ID Numbers: ALN-TTR02-003
2013-001644-65 ( EudraCT Number )
First Submitted: October 9, 2013
First Posted: October 14, 2013
Results First Submitted: August 30, 2018
Results First Posted: October 30, 2018
Last Update Posted: December 4, 2018