Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant

Alnylam Pharmaceuticals24 enrolled

Overview

The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of patisiran in participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression after liver transplant.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Amyloidosis, Familial Transthyretin Amyloidosis

Interventions

PatisiranDRUG

Patisiran was administered via IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Received liver transplant for treatment of hATTR amyloidosis ≥12 months before study start * Has increase in polyneuropathy disability (PND) score after liver transplant * Has received stable immunosuppressive regimen with ≤10 mg/day of prednisone for at least 3 months before study start * Has Karnofsky Performance Status (KPS) of ≥70% * Has vitamin A level greater than or equal to lower limit of normal Exclusion Criteria: * Has previously received inotersen or patisiran * Has clinically significant liver function test abnormalities * Has known portal hypertension with ascites * Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m\^2 * Has known leptomeningeal amyloidosis * Has infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV) * Has New York Heart Association heart failure classification of \>2 * Is wheelchair bound or bedridden * Has received organ transplants other than liver transplant * Will be using another tetramer stabilizer during the study

Locations (9)

Clinical Trial Site

Créteil, France

Clinical Trial Site

Le Kremlin-Bicêtre, France

Clinical Trial Site

Münster, Germany

Clinical Trial Site

Messina, Italy

Outcomes

Primary Outcomes

Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)

Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). The average of the percentage reduction in serum TTR observed at Month 6 and at Month 12 is first calculated for each patient and then the median (95% CI) of these averaged values is summarized for the Safety Analysis Set.

Time frame: Baseline, Months 6 and 12

Secondary Outcomes

Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12

The NIS is a composite neurologic impairment score that assesses motor weakness (NIS-W), sensation (NIS-S) and reflexes (NIS-R) by physical exam. The minimum and maximum values are 0 and 244, respectively. A higher score indicates a worse outcome.

Time frame: Baseline, Month 12

Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12

The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.

Time frame: Baseline, Month 12

Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12

The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.

Time frame: Baseline, Month 12

Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12

The COMPASS-31 questionnaire is a measure of autonomic neuropathy symptoms. The questions evaluate 6 autonomic domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.

Data from ClinicalTrials.gov

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