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

Phase 3

Completed

Conditions: Amyloidosis, Familial
Transthyretin Amyloidosis

Interventions: Drug: Patisiran

Registration Number: NCT03862807

Lead Sponsor: Alnylam Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patisiran	Patisiran	Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.

Primary Outcome Measures

Name	Time	Method
Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)	Baseline, Months 6 and 12	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12	Baseline, 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.
Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12	Baseline, Month 12	Nutritional status of participants 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.
Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12	Baseline, 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.
Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12	Baseline, 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.
Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12	Baseline, 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.
Percentage of Participants With Adverse Events	From baseline to end of study at Month 13	An AE is any untoward medical occurrence in a participant or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.