Clinical trial NCT02510261: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Participants Who Have Already Been Treated With ALN-TTR02 (Patisiran)
Official title: A Multicenter, Open-Label, Extension Study to Evaluate the Long-term Safety and Efficacy of Patisiran in Patients With Familial Amyloidotic Polyneuropathy Who Have Completed a Prior Patisiran Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyloidosis
Keywords: RNAi therapeutic
FAP
Familial Amyloid Polyneuropathy
TTR
Transthyretin
Amyloidosis
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-07-29
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: All the participants received only patisiran but divided into 3 arm groups based on administration in the parent study (placebo or patisiran in 003 \[NCT01961921\] or 004 \[NCT01960348\] studies).
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of long-term dosing with ALN-TTR02 (patisiran) in participants with transthyretin (TTR) mediated amyloidosis (ATTR).


Eligibility criteria: Inclusion Criteria:

* Have completed a patisiran study (i.e., completed the last efficacy visit in the parent study) and, in the opinion of the investigator, tolerated study drug
* Be willing and able to comply with the protocol-required visit schedule and visit requirements and provide written informed consent

Exclusion Criteria:

* Any new or uncontrolled condition that could make the participant unsuitable for participation

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation
timeFrame: First dose up to 28 days after last dose of study drug (approximately 5.6 years)
Secondary outcomes:
measure: Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3
timeFrame: Baseline, Year 3
measure: Change From Baseline in the NIS+7 Total Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Hand Grip Strength at Week 52
timeFrame: Baseline, Week 52
measure: Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage
timeFrame: Baseline, Year 5
measure: Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage
timeFrame: Baseline, Year 5
measure: Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Dermal Amyloid Burden at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5
timeFrame: Baseline, Year 5
measure: Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5
timeFrame: Baseline, Year 5
measure: Percent Change From Baseline in Serum TTR Levels at Year 5
timeFrame: Baseline, Year 5
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Clinical Trial Site
state: California
city: Aurora
country: United States
facility: Clinical Trial Site
state: Colorado
city: Jacksonville
country: United States
facility: Clinical Trial Site
state: Florida
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Detroit
country: United States
facility: Clinical Trial Site
state: Michigan
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Joplin
country: United States
facility: Clinical Trial Site
state: Missouri
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: Cooperstown
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Columbus
country: United States
facility: Clinical Trial Site
state: Ohio
city: Buenos Aires
country: Argentina
facility: Clinical Trial Site
city: Westmead
country: Australia
facility: Clinical Trial Site
city: Rio de Janeiro
country: Brazil
facility: Clinical Trial Site
city: São Paulo
country: Brazil
facility: Clinical Trial Site
city: Sofia
country: Bulgaria
facility: Clinical Trial Site
city: Vancouver
country: Canada
facility: Clinical Trial Site
state: British Columbia
city: Nicosia
country: Cyprus
facility: Clinical Trial Site
city: Fort De France
country: France
facility: Clinical Trial Site
state: Martinique
city: Saint-Pierre
country: France
facility: Clinical Trial Site
state: Reunion Island
city: Creteil
country: France
facility: Clinical Trial Site
city: Le Kremlin-bicetre
country: France
facility: Clinical Trial Site
city: Lille
country: France
facility: Clinical Trial Site
city: Marseille Cedex
country: France
facility: Clinical Trial Site
city: Cologne
country: Germany
facility: Clinical Trial Site
city: Heidelberg
country: Germany
facility: Clinical Trial Site
city: Muenster
country: Germany
facility: Clinical Trial Site
city: Pavia
country: Italy
facility: Clinical Trial Site
city: Rome
country: Italy
facility: Clinical Trial Site
city: Sicily
country: Italy
facility: Clinical Trial Site
city: Ehime
country: Japan
facility: Clinical Trial Site
city: Fukuoka
country: Japan
facility: Clinical Trial Site
city: Hiroshima
country: Japan
facility: Clinical Trial Site
city: Kumamoto
country: Japan
facility: Clinical Trial Site
city: Nagano
country: Japan
facility: Clinical Trial Site
city: Okawasuji
country: Japan
facility: Clinical Trial Site
city: Ono
country: Japan
facility: Clinical Trial Site
city: Ōita
country: Japan
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Kuala Lumpur
country: Malaysia
facility: Clinical Trial Site
city: Tlalpan
country: Mexico
facility: Clinical Trial Site
city: Groningen
country: Netherlands
facility: Clinical Trial Site
city: Lisbon
country: Portugal
facility: Clinical Trial Site
city: Porto
country: Portugal
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Huelva
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Palma De Mallorca
country: Spain
facility: Clinical Trial Site
city: Umeå
country: Sweden
facility: Clinical Trial Site
city: Taipei
country: Taiwan
facility: Clinical Trial Site
city: Taipei
country: Taiwan
facility: Clinical Trial Site
city: Istanbul
country: Turkey
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Adams D, Polydefkis M, Gonzalez-Duarte A, Wixner J, Kristen AV, Schmidt HH, Berk JL, Losada Lopez IA, Dispenzieri A, Quan D, Conceicao IM, Slama MS, Gillmore JD, Kyriakides T, Ajroud-Driss S, Waddington-Cruz M, Mezei MM, Plante-Bordeneuve V, Attarian S, Mauricio E, Brannagan TH 3rd, Ueda M, Aldinc E, Wang JJ, White MT, Vest J, Berber E, Sweetser MT, Coelho T; patisiran Global OLE study group. Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study. Lancet Neurol. 2021 Jan;20(1):49-59. doi: 10.1016/S1474-4422(20)30368-9. Epub 2020 Nov 16.