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

Study Overview
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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.

Official Title
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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)

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

Intervention / Treatment
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* Drug: patisiran (ALN-TTR02)
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: patisiran (ALN-TTR02)<br> | Drug: patisiran (ALN-TTR02)<br>* administered by intravenous (IV) infusion<br>|
| Placebo Comparator: Sterile Normal Saline (0.9% NaCl)<br> | Drug: Sterile Normal Saline (0.9% NaCl)<br>* administered by intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RNAi therapeutic, FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis