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

Amyloidosis, Hereditary Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01960348
• Other study ID #: ALN-TTR02-004
• Secondary ID: 2013-002987-17
• Status: Completed
• Phase: Phase 3
• Start date: November 2013
• Est. completion date: August 2017

Study information

• Verified date: November 2018
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• patisiran (ALN-TTR02)
administered by intravenous (IV) infusion
• Sterile Normal Saline (0.9% NaCl)
administered by intravenous (IV) infusion

Locations

Country	Name	City	State
Argentina	Clinical Trial Site	Buenos Aires
Australia	Clinical Trial Site	Westmead
Brazil	Clinical Trial Site	Ribeirao Preto
Brazil	Clinical Trial Site	Rio de Janeiro
Brazil	Clinical Trial Site	Sao Paulo
Bulgaria	Clinical Trial Site	Sofia
Canada	Clinical Trial Site	Vancouver	British Columbia
Cyprus	Clinical Trial Site	Nicosia
France	Clinical Trial Site	Bourdeaux
France	Clinical Trial Site	Creteil
France	Clinical Trial Site	Le Kremlin-bicetre
France	Clinical Trial Site	Lille Cedex
France	Clinical Trial Site	Marseille Cedex
Germany	Clinical Trial Site	Heidelberg
Germany	Clinical Trial Site	Muenster
Germany	Clinical Trial Site	Regensburg
Italy	Clinical Trial Site	Pavia
Italy	Clinical Trial Site	Rome
Italy	Clinical Trial Site	Sicily
Japan	Clinical Trial Site	Aichi
Japan	Clinical Trial Site	Kumamoto
Japan	Clinical Trial Site	Matsumoto	Nagano
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Malaysia	Clinical Trial Site	Kuala Lumpur
Mexico	Clinical Trial Site	Mexico City
Netherlands	Clinical Trial Site	Groningen
Portugal	Clinical Trial Site	Lisbon
Portugal	Clinical Trial Site	Porto
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Huelva
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Palma De Mallorca
Sweden	Clinical Trial Site	Umeå
Taiwan	Clinical Trial Site	Taipai
Taiwan	Clinical Trial Site	Taipei
Turkey	Clinical Trial Site	Istanbul
United Kingdom	Clinical Trial Site	London
United Kingdom	Clinical Trial Site	London
United States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Denver	Colorado
United States	Clinical Trial Site	Detroit	Michigan
United States	Clinical Trial Site	Durham	North Carolina
United States	Clinical Trial Site	La Mesa	California
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Orange	California
United States	Clinical Trial Site	Portland	Oregon
United States	Clinical Trial Site	Rochester	Minnesota
United States	Clinical Trial Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Cyprus,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Portugal,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire	The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in Norfolk QoL-DN at 18 months. The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.	18mo
Secondary	Neurological Impairment Score-Weakness (NIS-W) Score	The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in NIS-W at 18 months. NIS-W is a measure of motor strength, comprised of cranial nerve and both upper and lower limb motor assessments. The minimum and maximum values are 0 and 192, respectively. A higher score indicates a worse outcome.	18mo
Secondary	Rasch-built Overall Disability Scale (R-ODS) Score	The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in R-ODS score at 18 months. The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations in patients. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.	18mo
Secondary	Timed 10-meter Walk Test (10-MWT, Gait Speed)	The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in 10-MWT at 18 months. Ability to ambulate (gait speed) was assessed through the 10-meter walk test (10-MWT). The walk had to be completed without assistance from another person; ambulatory aids such as canes and walkers were permitted.	18mo
Secondary	Modified Body Mass Index (mBMI)	The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in mBMI at 18 months. The nutritional status of patients was evaluated using the mBMI; calculated as the product of BMI (weight in kilograms divided by the square of height in meters) and serum albumin (g/L).	18mo
Secondary	Autonomic Symptoms Questionnaire (Composite Autonomic Symptom Score [COMPASS 31])	The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in COMPASS 31 at 18 months. The COMPASS 31 is a measure of autonomic neuropathy symptoms. The questions evaluated 6 autonomic domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.	18mo