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)

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

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).

Study Overview

• Status: Completed
• Conditions: TTR-mediated Amyloidosis
• Intervention / Treatment: Drug: ALN-TTR02 (patisiran) administered by intravenous (IV) infusion

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Clinical Trial Site
• France
  • Le Kremlin-bicetre, France
    • Clinical Trial Site
  • Marseille Cedex, France
    • Clinical Trial Site
• Germany
  • Munster, Germany
    • Clinical Trial Site
• Portugal
  • Lisbon, Portugal
    • Clinical Trial Site
  • Porto, Portugal
    • Clinical Trial Site
• Spain
  • Palma De Mallorca, Spain
    • Clinical Trial Site
• Sweden
  • Umeå, Sweden
    • Clinical Trial Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALN-TTR02 (patisiran)	Drug: ALN-TTR02 (patisiran) administered by intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Baseline up to 56 days post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Serum TTR Levels	TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method.	From Baseline up to 56 days post last dose
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.	Baseline, Month 24
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).	Baseline, Month 24
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.	Baseline, Month 24
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.	Baseline, Month 24
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.	Baseline, Month 24

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: Jared Gollob, MD, Alnylam Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: October 9, 2013
• First Submitted That Met QC Criteria: October 11, 2013
• First Posted (Estimated): October 14, 2013

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: RNAi therapeutic
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: ALN-TTR02-003; 2013-001644-65 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.

Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.