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)

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Safety, Clinical Activity, and Pharmacokinetics of ALN-TTR02 in Patients With Familial Amyloidotic Polyneuropathy Who Have Previously Received ALN-TTR02

Conditions
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TTR-mediated Amyloidosis

Intervention / Treatment
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* Drug: ALN-TTR02 (patisiran) administered by intravenous (IV) infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously received and tolerated ALN-TTR02 (patisiran) in Study ALN-TTR02-002. Adequate Karnofsky performance status, liver function, and renal function. Exclusion Criteria: Pregnant or nursing. Has had a liver transplant. Has a New York Heart Association heart failure classification >2. Has unstable angina. Has uncontrolled clinically significant cardiac arrhythmia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALN-TTR02 (patisiran)<br> | Drug: ALN-TTR02 (patisiran) administered by intravenous (IV) infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RNAi therapeutic