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

Phase 3

Completed

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

Interventions: Drug: patisiran (ALN-TTR02)
Drug: Sterile Normal Saline (0.9% NaCl)

Registration Number: NCT01960348

Lead Sponsor: Alnylam Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 225

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
patisiran (ALN-TTR02)	patisiran (ALN-TTR02)	-
Sterile Normal Saline (0.9% NaCl)	Sterile Normal Saline (0.9% NaCl)	-

Primary Outcome Measures

Name	Time	Method
Modified Neuropathy Impairment Score +7 (mNIS+7)	18mo	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.

Secondary Outcome Measures

Name	Time	Method
Neurological Impairment Score-Weakness (NIS-W) Score	18mo	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.
Timed 10-meter Walk Test (10-MWT, Gait Speed)	18mo	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.
Rasch-built Overall Disability Scale (R-ODS) Score	18mo	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.
Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire	18mo	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.
Autonomic Symptoms Questionnaire (Composite Autonomic Symptom Score [COMPASS 31])	18mo	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.
Modified Body Mass Index (mBMI)	18mo	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).