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)

TTR-mediated Amyloidosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01961921
• Other study ID #: ALN-TTR02-003
• Secondary ID: 2013-001644-65
• Status: Completed
• Phase: Phase 2
• Start date: October 2013
• Est. completion date: August 2016

Study information

• Verified date: November 2018
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: August 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyloidosis
• TTR-mediated Amyloidosis

Intervention

Drug:
• ALN-TTR02 (patisiran) administered by intravenous (IV) infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  France,  Germany,  Portugal,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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