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)

NCT02510261 | Completed Phase 3 Results

• 2 other identifiers: ALN-TTR02-0062014-003877-40
• Study Type: interventional
• Target: 211
• Locations: 21 countries
• Sites: 56

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).

Conditions

Amyloidosis

Keywords

RNAi therapeutic; FAP; Familial Amyloid Polyneuropathy; TTR; Transthyretin; Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation

  AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

  First dose up to 28 days after last dose of study drug (approximately 5.6 years)

Secondary Outcomes (27)

• Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5

  Baseline, Year 5

• Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3

  Baseline, Year 3

• Change From Baseline in the NIS+7 Total Score at Week 52

  Baseline, Week 52

• Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5

  Baseline, Year 5

• Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5

  Baseline, Year 5

Study Arms (3)

Prior Placebo Group of Study 004

EXPERIMENTAL

Participants who received placebo and completed parent study ALN-TTR02-004 (NCT01960348) were enrolled to receive 0.3 milligrams per kilogram (mg/kg) patisiran intravenously (IV) once every 3 weeks (Q3W) up to 65.5 months.

Drug: Patisiran

Prior Patisiran Group of Study 004

EXPERIMENTAL

Participants who received patisiran and completed parent study ALN-TTR02-004 (NCT01960348) were enrolled to receive 0.3 mg/kg patisiran IV Q3W up to 66.9 months.

Drug: Patisiran

Prior Patisiran Group of Study 003

EXPERIMENTAL

Participants who received patisiran and completed parent study ALN-TTR02-003 (NCT01961921) were enrolled to receive 0.3 mg/kg patisiran IV Q3W up to 61.4 months.

Drug: Patisiran

Interventions

Patisiran DRUG

Patisiran was administered IV.

Also known as: ALN-TTR02

Prior Patisiran Group of Study 003; Prior Patisiran Group of Study 004; Prior Placebo Group of Study 004

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (56)

Clinical Trial Site

La Mesa, California, United States

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Aurora, Colorado, United States

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Jacksonville, Florida, 32224, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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Joplin, Missouri, 64804, United States

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St Louis, Missouri, United States

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Cooperstown, New York, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Columbus, Ohio, 43210, United States

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Buenos Aires, Argentina

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Westmead, Australia

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Sofia, Bulgaria

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Vancouver, British Columbia, Canada

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Nicosia, Cyprus

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Fort de France, Martinique, 97261, France

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Saint-Pierre, Reunion Island, 97448, France

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Créteil, France

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Le Kremlin-Bicêtre, France

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Lille, France

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Marseille, France

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Cologne, 50937, Germany

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Heidelberg, Germany

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Münster, Germany

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Pavia, Italy

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Rome, Italy

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Sicily, Italy

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Ehime, Japan

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Fukuoka, Japan

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Hiroshima, Japan

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Kumamoto, Japan

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Nagano, Japan

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Okawasuji, Japan

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Ono, Japan

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Ōita, Japan

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Kuala Lumpur, Malaysia

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Tlalpan, Mexico

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Groningen, Netherlands

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Lisbon, Portugal

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Porto, Portugal

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Seoul, South Korea

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Barcelona, Spain

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Huelva, Spain

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Madrid, Spain

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Palma de Mallorca, Spain

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Umeå, Sweden

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Taipei, 11217, Taiwan

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Taipei, Taiwan

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Istanbul, Turkey (Türkiye)

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London, United Kingdom

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Related Publications (3)

• Adams D, Wixner J, Polydefkis M, Berk JL, Conceicao IM, Dispenzieri A, Peltier A, Ueda M, Bender S, Capocelli K, Jay PY, Yureneva E, Obici L; patisiran Global OLE study group. Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension. JAMA Neurol. 2025 Mar 1;82(3):228-236. doi: 10.1001/jamaneurol.2024.4631.

  PMID: 39804640 DERIVED

• Lin KP, Yang CC, Lee YC, Lee MJ, Vest J, Sweetser MT, White MT, Badri P, Hsieh ST, Chao CC. Patisiran, an RNAi therapeutic for hereditary transthyretin-mediated amyloidosis: Sub-analysis in Taiwanese patients from the APOLLO study. J Formos Med Assoc. 2024 Sep;123(9):975-984. doi: 10.1016/j.jfma.2024.03.008. Epub 2024 Mar 27.

  PMID: 38548524 DERIVED

• 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.

  PMID: 33212063 DERIVED

MeSH Terms

Conditions

Amyloidosis; Amyloid Neuropathies, Familial

Interventions

patisiran

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Alnylam Pharmaceuticals Inc

Clinicaltrials@alnylam.com

866-330-0326

Study Officials

• Medical Director

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 29, 2015
• Study Start: July 16, 2015
• Primary Completion: November 23, 2022
• Study Completion: November 23, 2022
• Last Updated: December 6, 2023
• Results First Posted: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); DE (3); CY (1); BU (1); CA (1); BR (2); AR (1); FR (6); MY (1); ME (1); NL (1); TU (1); GB (1); IT (3); PT (2); ES (4); JP (8); AU (1); KR (1); SE (1); TW (2)