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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-001644-65 | EudraCT Number |
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The purpose of this study is to evaluate the safety and tolerability of long-term dosing with ALN-TTR02 (patisiran) in patients with transthyretin (TTR) mediated amyloidosis (ATTR).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALN-TTR02 (patisiran) | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALN-TTR02 (patisiran) administered by intravenous (IV) infusion | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation | 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. | From Baseline up to 56 days post last dose |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Serum TTR Levels | TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method. | From Baseline up to 56 days post last dose |
| Change From Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jared Gollob, MD | Alnylam Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Boston | Massachusetts | United States | |||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32641071 | Derived | Coelho T, Adams D, Conceicao I, Waddington-Cruz M, Schmidt HH, Buades J, Campistol J, Berk JL, Polydefkis M, Wang JJ, Chen J, Sweetser MT, Gollob J, Suhr OB. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis. 2020 Jul 8;15(1):179. doi: 10.1186/s13023-020-01399-4. |
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Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.
Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
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A total of 27 subjects were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | ALN-TTR02 (Patisiran) | Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 15, 2015 | Aug 30, 2018 |
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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. |
| Baseline, Month 24 |
| 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) | 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). | Baseline, Month 24 |
| Change in Gait Speed With 10-meter Walk Test | The 10-meter walk test measures the time (in seconds) that it takes a patient to walk 10 meters. | Baseline, Month 24 |
| Mean Change From Baseline in Hand Grip Strength | The mean (SEM) hand grip strength change from baseline at 24 months between patients who used patisiran with or without a concomitant TTR stabilizer. | Baseline, Month 24 |
| Change From Baseline in Nutritional Status (Modified Body Mass Index, mBMI) | 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. | Baseline, Month 24 |
| Rio de Janeiro |
| Brazil |
| Clinical Trial Site | Le Kremlin-Bicêtre | France |
| Clinical Trial Site | Marseille | France |
| Clinical Trial Site | Münster | Germany |
| Clinical Trial Site | Lisbon | Portugal |
| Clinical Trial Site | Porto | Portugal |
| Clinical Trial Site | Palma de Mallorca | Spain |
| Clinical Trial Site | Umeå | Sweden |
| COMPLETED |
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| NOT COMPLETED |
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All patients who received at least one dose of ALN-TTR02 (patisiran)
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| ID | Title | Description |
|---|---|---|
| BG000 | ALN-TTR02 (Patisiran) | Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Familial Amyloidotic Polyneuropathy (FAP) Stage | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation | 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. | Safety Analysis Set: All participants who received at least one dose of study drug. | Posted | Number | participants | From Baseline up to 56 days post last dose |
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| Secondary | Percentage Change From Baseline in Serum TTR Levels | TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method. | Full Analysis Set: All participants who were enrolled were included in the full analysis set. | Posted | Mean | Standard Error | Percent Change | From Baseline up to 56 days post last dose |
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| Secondary | Change From Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7) | 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. | 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. | Posted | Median | Full Range | score on a scale | Baseline, Month 24 |
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| Secondary | 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) | 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). | 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. | Posted | Median | Full Range | Score on a scale | Baseline, Month 24 |
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| Secondary | Change in Gait Speed With 10-meter Walk Test | The 10-meter walk test measures the time (in seconds) that it takes a patient to walk 10 meters. | 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. | Posted | Median | Full Range | m/sec | Baseline, Month 24 |
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| Secondary | Mean Change From Baseline in Hand Grip Strength | The mean (SEM) hand grip strength change from baseline at 24 months between patients who used patisiran with or without a concomitant TTR stabilizer. | 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. | Posted | Median | Full Range | kg | Baseline, Month 24 |
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| Secondary | Change From Baseline in Nutritional Status (Modified Body Mass Index, mBMI) | 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. | 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. | Posted | Median | Full Range | kg/m^2 x albumin g/L | Baseline, Month 24 |
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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).
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Safety Population | All patients who received at least one dose of ALN-TTR02 (patisiran) | 2 | 27 | 7 | 27 | 26 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac amyloidosis | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
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| Abscess limb | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Osteomyelitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Femur fracture | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Foot fracture | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Ligament rupture | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Tibia fracture | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
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| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.0) | Systematic Assessment |
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| Acute prerenal failure | Renal and urinary disorders | MedDRA (18.0) | Systematic Assessment |
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| Arthrodesis | Surgical and medical procedures | MedDRA (18.0) | Systematic Assessment |
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| Venous thrombosis limb | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flushing | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Infusion related reaction | Immune system disorders | MedDRA (18.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Wound | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
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| Neuralgia | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA (18.0) | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Cataract | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Infusion site extravasation | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Macular degeneration | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Macular fibrosis | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Visual acuity reduced | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Early satiety | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Gait disturbance | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Infusion site erythema | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Pain | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Foot fracture | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Blood thyroid stimulating hormone decreased | Investigations | MedDRA (18.0) | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA (18.0) | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Visual field defect | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Alnylam Pharmaceuticals Inc | 1-877-256-9526 | Clinicaltrials@alnylam.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 14, 2016 | Aug 30, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000606954 | patisiran |
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| FAP Stage III: Wheelchair-bound or bedridden |
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| Title | Measurements |
|---|---|
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Individual TTR % change |
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| Individual Predose TTR % change |
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| Individual Max TTR % change |
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