NCT01960348

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of patisiran (ALN-TTR02) in patients with transthyretin (TTR) mediated amyloidosis. An open-label, single-arm, long-term follow-up extension study NCT02510261 (ALN-TTR02-006) was initiated to provide participants who completed this study with continued patisiran-LNP (lipid nanoparticle) treatment.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
225

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Nov 2013

Typical duration for phase_3

Geographic Reach
21 countries

52 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 9, 2013

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 10, 2013

Completed
22 days until next milestone

Study Start

First participant enrolled

November 1, 2013

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2017

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

September 6, 2018

Completed
Last Updated

April 22, 2024

Status Verified

November 1, 2018

Enrollment Period

3.8 years

First QC Date

October 9, 2013

Results QC Date

August 7, 2018

Last Update Submit

April 17, 2024

Conditions

Keywords

RNAi therapeuticFAPFamilial Amyloid PolyneuropathyTTRTransthyretinAmyloidosis

Outcome Measures

Primary Outcomes (1)

  • Modified Neuropathy Impairment Score +7 (mNIS+7)

    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in mNIS+7 at 18 months. The mNIS+7 is a composite score that quantitates motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.

    18mo

Secondary Outcomes (6)

  • Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire

    18mo

  • Neurological Impairment Score-Weakness (NIS-W) Score

    18mo

  • Rasch-built Overall Disability Scale (R-ODS) Score

    18mo

  • Timed 10-meter Walk Test (10-MWT, Gait Speed)

    18mo

  • Modified Body Mass Index (mBMI)

    18mo

  • +1 more secondary outcomes

Study Arms (2)

patisiran (ALN-TTR02)

ACTIVE COMPARATOR
Drug: patisiran (ALN-TTR02)

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR
Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

administered by intravenous (IV) infusion

patisiran (ALN-TTR02)

administered by intravenous (IV) infusion

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female of 18 to 85 years of age (inclusive);
  • Have a diagnosis of FAP
  • Neuropathy Impairment Score requirement of 5-130
  • Meet Karnofsky performance status requirements
  • Have adequate complete blood counts and liver function tests
  • Have adequate cardiac function
  • Have negative serology for hepatitis B virus (HBV) and hepatitis C virus (HCV)

You may not qualify if:

  • Had a prior liver transplant or is planned to undergo liver transplant during the study period;
  • Has untreated hypo- or hyperthyroidism;
  • Has known human immunodeficiency virus (HIV) infection;
  • Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated;
  • Recently received an investigational agent or device
  • Is currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (52)

Clinical Trial Site

La Mesa, California, United States

Location

Clinical Trial Site

Orange, California, United States

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Clinical Trial Site

Denver, Colorado, United States

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Clinical Trial Site

Chicago, Illinois, United States

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Clinical Trial Site

Baltimore, Maryland, United States

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Clinical Trial Site

Boston, Massachusetts, United States

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Clinical Trial Site

Detroit, Michigan, United States

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Clinical Trial Site

Rochester, Minnesota, United States

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Clinical Trial Site

St Louis, Missouri, United States

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Clinical Trial Site

New York, New York, 10029, United States

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Clinical Trial Site

New York, New York, 10032, United States

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Clinical Trial Site

Durham, North Carolina, United States

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Clinical Trial Site

Portland, Oregon, United States

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Clinical Trial Site

Buenos Aires, Argentina

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Clinical Trial Site

Westmead, Australia

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Clinical Trial Site

Ribeirão Preto, Brazil

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Clinical Trial Site

Rio de Janeiro, Brazil

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Clinical Trial Site

São Paulo, Brazil

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Clinical Trial Site

Sofia, Bulgaria

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Clinical Trial Site

Vancouver, British Columbia, Canada

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Clinical Trial Site

Nicosia, Cyprus

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Clinical Trial Site

Bourdeaux, France

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Clinical Trial Site

Créteil, France

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Clinical Trial Site

Le Kremlin-Bicêtre, France

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Clinical Trial Site

Lille, France

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Clinical Trial Site

Marseille, France

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Clinical Trial Site

Heidelberg, Germany

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Clinical Trial Site

Münster, Germany

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Clinical Trial Site

Regensburg, Germany

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Clinical Trial Site

Pavia, Italy

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Clinical Trial Site

Rome, Italy

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Clinical Trial Site

Sicily, Italy

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Clinical Trial Site

Matsumoto, Nagano, Japan

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Clinical Trial Site

Aichi, Japan

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Clinical Trial Site

Kumamoto, Japan

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Clinical Trial Site

Kuala Lumpur, Malaysia

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Clinical Trial Site

Mexico City, Mexico

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Clinical Trial Site

Groningen, Netherlands

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Clinical Trial Site

Lisbon, Portugal

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Clinical Trial Site

Porto, Portugal

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Clinical Trial Site

Seoul, 135-710, South Korea

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Clinical Trial Site

Seoul, 143-729, South Korea

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Clinical Trial Site

Barcelona, Spain

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Clinical Trial Site

Huelva, Spain

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Madrid, Spain

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Clinical Trial Site

Palma de Mallorca, Spain

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Clinical Trial Site

Umeå, Sweden

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Clinical Trial Site

Taipai, 11217, Taiwan

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Clinical Trial Site

Taipei, 10002, Taiwan

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Clinical Trial Site

Istanbul, Turkey (Türkiye)

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Clinical Trial Site

London, NW32PF, United Kingdom

Location

Clinical Trial Site

London, SW17 0RE, United Kingdom

Location

Related Publications (7)

  • 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.

  • Quan D, Obici L, Berk JL, Ando Y, Aldinc E, White MT, Adams D. Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial. Amyloid. 2023 Mar;30(1):49-58. doi: 10.1080/13506129.2022.2118043. Epub 2022 Sep 18.

  • Zhang X, Goel V, Attarwala H, Sweetser MT, Clausen VA, Robbie GJ. Patisiran Pharmacokinetics, Pharmacodynamics, and Exposure-Response Analyses in the Phase 3 APOLLO Trial in Patients With Hereditary Transthyretin-Mediated (hATTR) Amyloidosis. J Clin Pharmacol. 2020 Jan;60(1):37-49. doi: 10.1002/jcph.1480. Epub 2019 Jul 19.

  • Minamisawa M, Claggett B, Adams D, Kristen AV, Merlini G, Slama MS, Dispenzieri A, Shah AM, Falk RH, Karsten V, Sweetser MT, Chen J, Riese R, Vest J, Solomon SD. Association of Patisiran, an RNA Interference Therapeutic, With Regional Left Ventricular Myocardial Strain in Hereditary Transthyretin Amyloidosis: The APOLLO Study. JAMA Cardiol. 2019 May 1;4(5):466-472. doi: 10.1001/jamacardio.2019.0849.

  • Solomon SD, Adams D, Kristen A, Grogan M, Gonzalez-Duarte A, Maurer MS, Merlini G, Damy T, Slama MS, Brannagan TH 3rd, Dispenzieri A, Berk JL, Shah AM, Garg P, Vaishnaw A, Karsten V, Chen J, Gollob J, Vest J, Suhr O. Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis. Circulation. 2019 Jan 22;139(4):431-443. doi: 10.1161/CIRCULATIONAHA.118.035831.

  • Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153.

  • Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J, Gollob J, Coelho T. Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol. 2017 Sep 11;17(1):181. doi: 10.1186/s12883-017-0948-5.

MeSH Terms

Conditions

Amyloidosis, FamilialAmyloid Neuropathies, FamilialAmyloid NeuropathiesAmyloidosis, Hereditary, Transthyretin-RelatedAmyloidosis

Interventions

patisiran

Condition Hierarchy (Ancestors)

Metabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesProteostasis DeficienciesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesNervous System DiseasesPeripheral Nervous System DiseasesNeuromuscular Diseases

Results Point of Contact

Title
Chief Medical Officer
Organization
Alnylam Pharmaceuticals, Inc.

Study Officials

  • Jared Gollob

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

October 9, 2013

First Posted

October 10, 2013

Study Start

November 1, 2013

Primary Completion

August 1, 2017

Study Completion

August 1, 2017

Last Updated

April 22, 2024

Results First Posted

September 6, 2018

Record last verified: 2018-11

Data Sharing

IPD Sharing
Will share

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.

Locations