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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01960348




Registration number
NCT01960348
Ethics application status
Date submitted
9/10/2013
Date registered
10/10/2013
Date last updated
11/12/2018

Titles & IDs
Public title
APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis
Scientific 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)
Secondary ID [1] 0 0
2013-002987-17
Secondary ID [2] 0 0
ALN-TTR02-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
TTR-mediated Amyloidosis 0 0
Amyloidosis, Hereditary 0 0
Amyloid Neuropathies, Familial 0 0
Familial Amyloid Polyneuropathies 0 0
Amyloid Neuropathies 0 0
Amyloidosis, Hereditary, Transthyretin-Related 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - patisiran (ALN-TTR02)
Treatment: Drugs - Sterile Normal Saline (0.9% NaCl)

Active Comparator: patisiran (ALN-TTR02) -

Placebo Comparator: Sterile Normal Saline (0.9% NaCl) -


Treatment: Drugs: patisiran (ALN-TTR02)
administered by intravenous (IV) infusion

Treatment: Drugs: Sterile Normal Saline (0.9% NaCl)
administered by intravenous (IV) infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
18mo
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
18mo
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
18mo
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
18mo
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
18mo
Secondary outcome [5] 0 0
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).
Timepoint [5] 0 0
18mo
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
18mo

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Clinical Trial Site - Westmead
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Brazil
State/province [13] 0 0
Ribeirao Preto
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio de Janeiro
Country [15] 0 0
Brazil
State/province [15] 0 0
Sao Paulo
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Sofia
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Cyprus
State/province [18] 0 0
Nicosia
Country [19] 0 0
France
State/province [19] 0 0
Bourdeaux
Country [20] 0 0
France
State/province [20] 0 0
Creteil
Country [21] 0 0
France
State/province [21] 0 0
Le Kremlin-bicetre
Country [22] 0 0
France
State/province [22] 0 0
Lille Cedex
Country [23] 0 0
France
State/province [23] 0 0
Marseille Cedex
Country [24] 0 0
Germany
State/province [24] 0 0
Heidelberg
Country [25] 0 0
Germany
State/province [25] 0 0
Muenster
Country [26] 0 0
Germany
State/province [26] 0 0
Regensburg
Country [27] 0 0
Italy
State/province [27] 0 0
Pavia
Country [28] 0 0
Italy
State/province [28] 0 0
Rome
Country [29] 0 0
Italy
State/province [29] 0 0
Sicily
Country [30] 0 0
Japan
State/province [30] 0 0
Nagano
Country [31] 0 0
Japan
State/province [31] 0 0
Aichi
Country [32] 0 0
Japan
State/province [32] 0 0
Kumamoto
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Seoul
Country [34] 0 0
Malaysia
State/province [34] 0 0
Kuala Lumpur
Country [35] 0 0
Mexico
State/province [35] 0 0
Mexico City
Country [36] 0 0
Netherlands
State/province [36] 0 0
Groningen
Country [37] 0 0
Portugal
State/province [37] 0 0
Lisbon
Country [38] 0 0
Portugal
State/province [38] 0 0
Porto
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Spain
State/province [40] 0 0
Huelva
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Palma De Mallorca
Country [43] 0 0
Sweden
State/province [43] 0 0
Umeå
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipai
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taipei
Country [46] 0 0
Turkey
State/province [46] 0 0
Istanbul
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alnylam Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT01960348
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jared Gollob
Address 0 0
Alnylam Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications