Clinical trial NCT01960348: APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis
Official title: APOLLO: A Phase 3 Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Patisiran (ALN-TTR02) in Transthyretin (TTR)-Mediated Polyneuropathy (Familial Amyloidotic Polyneuropathy-FAP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: TTR-mediated Amyloidosis
Amyloidosis, Hereditary
Amyloid Neuropathies, Familial
Familial Amyloid Polyneuropathies
Amyloid Neuropathies
Amyloidosis, Hereditary, Transthyretin-Related
Keywords: RNAi therapeutic
FAP
Familial Amyloid Polyneuropathy
TTR
Transthyretin
Amyloidosis
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-10-10
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Modified Neuropathy Impairment Score +7 (mNIS+7)
timeFrame: 18mo
Secondary outcomes:
measure: Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire
timeFrame: 18mo
measure: Neurological Impairment Score-Weakness (NIS-W) Score
timeFrame: 18mo
measure: Rasch-built Overall Disability Scale (R-ODS) Score
timeFrame: 18mo
measure: Timed 10-meter Walk Test (10-MWT, Gait Speed)
timeFrame: 18mo
measure: Modified Body Mass Index (mBMI)
timeFrame: 18mo
measure: Autonomic Symptoms Questionnaire (Composite Autonomic Symptom Score [COMPASS 31])
timeFrame: 18mo
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Clinical Trial Site
state: California
city: Orange
country: United States
facility: Clinical Trial Site
state: California
city: Denver
country: United States
facility: Clinical Trial Site
state: Colorado
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: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
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: Durham
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Portland
country: United States
facility: Clinical Trial Site
state: Oregon
city: Buenos Aires
country: Argentina
facility: Clinical Trial Site
city: Westmead
country: Australia
facility: Clinical Trial Site
city: Ribeirao Preto
country: Brazil
facility: Clinical Trial Site
city: Rio de Janeiro
country: Brazil
facility: Clinical Trial Site
city: Sao 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: Bourdeaux
country: France
facility: Clinical Trial Site
city: Creteil
country: France
facility: Clinical Trial Site
city: Le Kremlin-bicetre
country: France
facility: Clinical Trial Site
city: Lille Cedex
country: France
facility: Clinical Trial Site
city: Marseille Cedex
country: France
facility: Clinical Trial Site
city: Heidelberg
country: Germany
facility: Clinical Trial Site
city: Muenster
country: Germany
facility: Clinical Trial Site
city: Regensburg
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: Matsumoto
country: Japan
facility: Clinical Trial Site
state: Nagano
city: Aichi
country: Japan
facility: Clinical Trial Site
city: Kumamoto
country: Japan
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Kuala Lumpur
country: Malaysia
facility: Clinical Trial Site
city: Mexico City
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: Taipai
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
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Jared Gollob
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.