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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01961921

Enrollment

Registered

2013-10-14

Start date

2013-10-31

Completion date

2016-08-31

Last updated

2024-04-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

TTR-mediated Amyloidosis

Keywords

RNAi therapeutic

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).

Interventions

DRUGALN-TTR02 (patisiran) administered by intravenous (IV) infusion

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

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.

Design outcomes

Primary

Measure	Time frame	Description
The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation	From Baseline up to 56 days post last dose	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

Measure	Time frame	Description
Change From Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7)	Baseline, Month 24	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)	Baseline, Month 24	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).
Percentage Change From Baseline in Serum TTR Levels	From Baseline up to 56 days post last dose	TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method.
Mean Change From Baseline in Hand Grip Strength	Baseline, Month 24	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)	Baseline, Month 24	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.
Change in Gait Speed With 10-meter Walk Test	Baseline, Month 24	The 10-meter walk test measures the time (in seconds) that it takes a patient to walk 10 meters.

Countries

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

Participant flow

Recruitment details

A total of 27 subjects were enrolled.

Participants by arm

Arm	Count
ALN-TTR02 (Patisiran) Patients received 0.3 mg/kg of ALN-TTR02 (patisiran) every three weeks	27
Total	27

Baseline characteristics

Characteristic	ALN-TTR02 (Patisiran)
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	13 Participants
Age, Categorical Between 18 and 65 years	14 Participants
Age, Continuous	57.9 years STANDARD_DEVIATION 15.36
Familial Amyloidotic Polyneuropathy (FAP) Stage FAP Stage II: Assistance with ambulation required	3 Participants
Familial Amyloidotic Polyneuropathy (FAP) Stage FAP Stage III: Wheelchair-bound or bedridden	0 Participants
Familial Amyloidotic Polyneuropathy (FAP) Stage FAP Stage I: Unimpaired ambulation	24 Participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	18 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	2 / 27
other Total, other adverse events	26 / 27
serious Total, serious adverse events	7 / 27

Outcome results

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.

Time frame: From Baseline up to 56 days post last dose

Population: Safety Analysis Set: All participants who received at least one dose of study drug.

Arm	Measure	Group	Value (NUMBER)
ALN-TTR02 (Patisiran)	The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation	At least 1 Treatment Emergent Adverse Event (TAE)	26 participants
ALN-TTR02 (Patisiran)	The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation	At least 1 Serious Adverse Event (SAE)	7 participants
ALN-TTR02 (Patisiran)	The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation	Study Drug Discontinuation for any reason	2 participants

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.