APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis

NCT ID: NCT01960348

Last Updated: 2024-04-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2017-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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TTR-mediated Amyloidosis Amyloidosis, Hereditary Amyloid Neuropathies, Familial Familial Amyloid Polyneuropathies Amyloid Neuropathies Amyloidosis, Hereditary, Transthyretin-Related

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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patisiran (ALN-TTR02)

Group Type ACTIVE_COMPARATOR

patisiran (ALN-TTR02)

Intervention Type DRUG

administered by intravenous (IV) infusion

Sterile Normal Saline (0.9% NaCl)

Group Type PLACEBO_COMPARATOR

Sterile Normal Saline (0.9% NaCl)

Intervention Type DRUG

administered by intravenous (IV) infusion

Interventions

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patisiran (ALN-TTR02)

administered by intravenous (IV) infusion

Intervention Type DRUG

Sterile Normal Saline (0.9% NaCl)

administered by intravenous (IV) infusion

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alnylam Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jared Gollob

Role: STUDY_DIRECTOR

Alnylam Pharmaceuticals

Locations

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Clinical Trial Site

La Mesa, California, United States

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Orange, California, United States

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Denver, Colorado, 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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St Louis, Missouri, United States

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New York, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Portland, Oregon, United States

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Buenos Aires, , Argentina

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Westmead, , Australia

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Ribeirão Preto, , Brazil

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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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Bourdeaux, , 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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Heidelberg, , Germany

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Münster, , Germany

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Regensburg, , Germany

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Pavia, , Italy

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Rome, , Italy

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Sicily, , Italy

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Matsumoto, Nagano, Japan

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Aichi, , Japan

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Kumamoto, , Japan

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Kuala Lumpur, , Malaysia

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Mexico City, , 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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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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Taipai, , 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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London, , United Kingdom

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Countries

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United States Argentina Australia Brazil Bulgaria Canada Cyprus France Germany Italy Japan Malaysia Mexico Netherlands Portugal South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38548524 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36120830 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31322739 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30878017 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30586695 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29972753 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28893208 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-002987-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALN-TTR02-004

Identifier Type: -

Identifier Source: org_study_id

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