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

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

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

Study Overview

• Status: Completed
• Conditions: Polyneuropathy; Hereditary Transthyretin-mediated (ATTRv) Amyloidosis
• Intervention / Treatment: Drug: Patisiran

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Clinical Trial Site
    • San Diego, California, United States, 92103
      • Clinical Trial Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Trial Site
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • Clinical Trial Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Clinical Trial Site
    • Tampa, Florida, United States, 33609
      • Clinical Trial Site
  • Georgia
    • Braselton, Georgia, United States, 30517
      • Clinical Trial Site
    • Macon, Georgia, United States, 31201
      • Clinical Trial Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Clinical Trial Site
    • Chicago, Illinois, United States, 60612
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Clinical Trial Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Clinical Trial Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Clinical Trial Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Trial Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Clinical Trial Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Clinical Trial Site
    • Charlotte, North Carolina, United States, 28207
      • Clinical Trial Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Clinical Trial Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Clinical Trial Site
    • Bethlehem, Pennsylvania, United States, 18015
      • Clinical Trial Site
    • Lancaster, Pennsylvania, United States, 17602
      • Clinical Trial Site
    • Pittsburgh, Pennsylvania, United States, 15232
      • Clinical Trial Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Clinical Trial Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Clinical Trial Site
  • Texas
    • Austin, Texas, United States, 78756
      • Clinical Trial Site
    • San Antonio, Texas, United States, 78229
      • Clinical Trial Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with ATTRv amyloidosis with polyneuropathy who have a V122I or T60A mutation

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patisiran Prospective Cohort; Patients who are naive to patisiran at study enrollment with the intention to initiate commercial patisiran therapy.	Drug: Patisiran; Patisiran-lipid complex injection, for intravenous use; Other Names: ONPATTRO; ALN-TTR02
Patisiran Mixed Cohort; Patients who are currently on commercial patisiran therapy for less than 12 months at study enrollment.	Drug: Patisiran; Patisiran-lipid complex injection, for intravenous use; Other Names: ONPATTRO; ALN-TTR02
Patisiran Retrospective Cohort; 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; Patisiran-lipid complex injection, for intravenous use; Other Names: ONPATTRO; ALN-TTR02

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2019
• Primary Completion (ACTUAL): May 24, 2022
• Study Completion (ACTUAL): May 24, 2022

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: December 13, 2019
• First Posted (ACTUAL): December 17, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 3, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Neurodegenerative diseases; Polyneuropathies; TTR; Amyloidosis; RNAi therapeutic; Nervous system diseases; ATTR; Metabolic diseases; Transthyretin; FAP; V122I; Transthyretin amyloidosis; Amyloid neuropathies; Amyloid neuropathies, familial; Amyloidosis, familial; Familial Amyloid Polyneuropathies; Genetic diseases, inborn; Neuromuscular diseases; TTR-mediated Amyloidosis; Valine to isoleucine substitution at position 122; Threonine to alanine substitution at position 60; T60A; Peripheral nervous system diseases; Proteostasis deficiencies; Heredodegenerative disorders, nervous system; Metabolism, inborn errors; ATTRv
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Proteostasis Deficiencies; Amyloidosis; Polyneuropathies
• Other Study ID Numbers: ALN-TTR02-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No