A Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of ATTRv Amyloidosis With a V122I or T60A Mutation

Study Overview
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Brief Summary
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To evaluate the effectiveness of patisiran in patients with ATTRv amyloidosis with polyneuropathy who have a V122I or T60A mutation.

Official Title
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A Phase 4 Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of Hereditary Transthyretin-Mediated (ATTRv) Amyloidosis With a V122I or T60A Mutation

Conditions
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Hereditary Transthyretin-mediated (ATTRv) Amyloidosis, Polyneuropathy

Intervention / Treatment
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* Drug: Patisiran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with ATTRv amyloidosis with polyneuropathy, with a documented V122I or T60A mutation PND score of I-IIIB at baseline. Exposure to commercial patisiran in one of the 3 cohorts: Prospective Cohort: Naive to patisiran treatment at the time of enrollment with intention to initiate treatment with patisiran. Mixed cohort: Currently on commercial patisiran therapy for less than 12 months at study enrollment. Retrospective cohort: Exposed to commercial patisiran treatment for at least 12 months prior to study enrollment, regardless of current treatment status at enrollment. Exclusion Criteria: New York Heart Association (NYHA) heart failure classification ≥3 Karnofsky Performance Status (KPS) <60% Unstable congestive heart failure (CHF) Known primary amyloidosis (AL) or leptomeningeal amyloidosis Prior major organ transplant Previously received patisiran Previous treatment with a TTR silencing therapy

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patisiran Prospective Cohort<br>Patients who are naive to patisiran at study enrollment with the intention to initiate commercial patisiran therapy. | Drug: Patisiran<br>* Patisiran-lipid complex injection, for intravenous use<br>* Other names: ALN-TTR02;|
| Patisiran Mixed Cohort<br>Patients who are currently on commercial patisiran therapy for less than 12 months at study enrollment. | Drug: Patisiran<br>* Patisiran-lipid complex injection, for intravenous use<br>* Other names: ALN-TTR02;|
| Patisiran Retrospective Cohort<br>Patients who have been on commercial patisiran therapy for at least 12 months prior to study enrollment, regardless of current treatment status at enrollment. | Drug: Patisiran<br>* Patisiran-lipid complex injection, for intravenous use<br>* Other names: ALN-TTR02;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Stable or Improved Polyneuropathy Disability (PND) Score at 12 Months Relative to Baseline | PND Scores: Stage 0=No symptoms, Stage 1=Sensory disturbances but preserved walking capability, Stage 2=Impaired walking capacity, but ability to walk without a stick or crutches, Stage 3A/B=Walking with the help of 1 or 2 sticks or crutches, Stage 4=confined to wheel chair or bedridden. | Baseline, Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TTR, Valine to isoleucine substitution at position 122, V122I, Threonine to alanine substitution at position 60, T60A, Familial Amyloid Polyneuropathies, ATTR, Transthyretin amyloidosis, Transthyretin, Amyloidosis, TTR-mediated Amyloidosis, RNAi therapeutic, FAP, Polyneuropathies, Amyloid neuropathies, Amyloid neuropathies, familial, Amyloidosis, familial, Peripheral nervous system diseases, Nervous system diseases, Neuromuscular diseases, Proteostasis deficiencies, Metabolic diseases, Heredodegenerative disorders, nervous system, Neurodegenerative diseases, Genetic diseases, inborn, Metabolism, inborn errors, ATTRv