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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)

Primary Purpose

TTR-mediated Amyloidosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ALN-TTR02 (patisiran) administered by intravenous (IV) infusion
Sponsored by
Alnylam Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for TTR-mediated Amyloidosis focused on measuring RNAi therapeutic

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ALN-TTR02 (patisiran)

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Percentage Change From Baseline in Serum TTR Levels
TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method.
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.
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).
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.
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.
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.

Full Information

First Posted
October 9, 2013
Last Updated
November 8, 2018
Sponsor
Alnylam Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01961921
Brief Title
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)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
TTR-mediated Amyloidosis
Keywords
RNAi therapeutic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ALN-TTR02 (patisiran)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ALN-TTR02 (patisiran) administered by intravenous (IV) infusion
Primary Outcome Measure Information:
Title
The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation
Description
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.
Time Frame
From Baseline up to 56 days post last dose
Secondary Outcome Measure Information:
Title
Percentage Change From Baseline in Serum TTR Levels
Description
TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method.
Time Frame
From Baseline up to 56 days post last dose
Title
Change From Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7)
Description
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.
Time Frame
Baseline, Month 24
Title
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)
Description
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).
Time Frame
Baseline, Month 24
Title
Change in Gait Speed With 10-meter Walk Test
Description
The 10-meter walk test measures the time (in seconds) that it takes a patient to walk 10 meters.
Time Frame
Baseline, Month 24
Title
Mean Change From Baseline in Hand Grip Strength
Description
The mean (SEM) hand grip strength change from baseline at 24 months between patients who used patisiran with or without a concomitant TTR stabilizer.
Time Frame
Baseline, Month 24
Title
Change From Baseline in Nutritional Status (Modified Body Mass Index, mBMI)
Description
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.
Time Frame
Baseline, Month 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jared Gollob, MD
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Clinical Trial Site
City
Rio de Janeiro
Country
Brazil
Facility Name
Clinical Trial Site
City
Le Kremlin-bicetre
Country
France
Facility Name
Clinical Trial Site
City
Marseille Cedex
Country
France
Facility Name
Clinical Trial Site
City
Munster
Country
Germany
Facility Name
Clinical Trial Site
City
Lisbon
Country
Portugal
Facility Name
Clinical Trial Site
City
Porto
Country
Portugal
Facility Name
Clinical Trial Site
City
Palma De Mallorca
Country
Spain
Facility Name
Clinical Trial Site
City
Umeå
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
32641071
Citation
Coelho T, Adams D, Conceicao I, Waddington-Cruz M, Schmidt HH, Buades J, Campistol J, Berk JL, Polydefkis M, Wang JJ, Chen J, Sweetser MT, Gollob J, Suhr OB. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis. 2020 Jul 8;15(1):179. doi: 10.1186/s13023-020-01399-4.
Results Reference
derived

Learn more about this trial

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)

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