Spectrum of Peripheral and Autonomic Neuropathies in Patients With aTTRwt Amyloidosis and Response to Patisiran Therapy

NCT05023889 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 001 amendment 02
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of patisiran in patients with wtATTR amyloidosis and symptomatic polyneuropathy by evaluating the effect on neurologic impairment and quality of life.

Conditions

Wild Type ATTR Amyloidosis; Polyneuropathies; Wild-Type Transthyretin-Related (ATTR)Amyloidosis; Wild-Type Transthyretin Cardiac Amyloidosis; Transthyretin Amyloidosis

Outcome Measures

Primary Outcomes (3)

• Change in Neurological Impairment Score

  to assess the severity of functional impairment of motor and sensory nerves.NIS 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.

  baseline to 24 months

• Norfolk QOL-DN

  Change in Norfolk Quality of Life Questionnaire (Norfolk QOL-DN).The change from baseline in Norfolk QoL-DN at 24 months. The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure 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.

  baseline to 24 months

• COMPASS 31score

  Composite Autonomic Symptom Score (COMPASS) 31a self-assessment instrument for patient reported autonomic symptoms such as dizziness, constipation, diarrhea, nausea/vomiting, and incontinence. The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome

  baseline to 24 months

Secondary Outcomes (6)

• PND Polyneuropathy disability (PND) Score

  baseline to 24 months

• Karnofsky, performance status score

  baseline to 24 months

• EuroQOL

  baseline to 24 months

• EMG -Electromyography

  baseline to 24 months

• Tilt Table Test

  24 months

Other Outcomes (5)

• Cardiac MRI

  start of study, and study end at 2 years

• Echo with strain

  start of study, and study end at 2 years

• PYP - mTc99-PYP

  start of study, and study end at 2 years

Study Arms (1)

open label

OTHER

single open arm label

Drug: patisiran

Interventions

patisiran DRUG

Patients will receive 0.3 mg/kg patisiran once every 21 days administered as an IV infusion over 70 minutes (approximately 1 mL/minute for the first 15 minutes followed by approximately 3 mL/minute for the remainder of the infusion) by a controlled infusion device. All patients in this study will be premedicated prior to dosing with patisiran. Study drug supplied for this study must not be used for any purpose other than the present study and must not be administered to any person not enrolled in the study. The first dose of study drug (week 1) will be administered under the supervision of site personnel. After the first dose of patisiran, patients should return to the site for patisiran dosing once every 21 days or receive the patisiran infusions at a local infusion center by a healthcare professional trained on the Protocol, administration of premedication, and patisiran infusion. Patient must receive a dose of interventional drug within the dosing window (±3 days).

Also known as: ONPATTRO

open label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female \>18
• Diagnosis of symptomatic polyneuropathy
• wtATTR based on cardiac biopsy or Tc99m PYP
• Negative hATTR sequencing
• to 0.5 gram/dl serum monoclonal protein.
• No history of other secondary causes of neuropathy.
• Have adequate complete blood counts and liver function tests
• Have negative serology for hepatitis B virus (HBV) and hepatitis C virus (HCV)

You may not qualify if:

• Other Causes of neuropathy as determined by the principle investigator.
• Has known human immunodeficiency virus (HIV) infection;
• Primary AL.
• NYHA Class IV at the Screening visit. 5. Has any of the following laboratory parameter assessments at screening:
• Aspartate transaminase (AST) or alanine transaminase (ALT) levels ˃2.0 × the upper limit of normal (ULN).
• Total bilirubin ˃ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert's syndrome are eligible if total bilirubin \<2 × ULN.
• International normalized ratio (INR) ˃1.5 (unless patient is on anticoagulant therapy, in which case excluded if INR ˃3.5).
• \. Has eGFR \< 30 mL/min/1.73 m2 (using the modification of diet in renal disease \[MDRD\] formula). 7. Is currently taking diflunisal; if previously on this agent, must have at least a 6-month wash-out prior to dosing (Day 1).
• \. Is currently taking doxycycline, or tauroursodeoxycholic acid; if previously on any of these agents must have completed a 30-day wash-out prior to dosing (Day 1).
• \. Requires treatment with calcium channel blockers (eg, verapamil, diltiazem) or digitalis.
• \. Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease.
• \. Has non-amyloid disease affecting exercise testing (eg, severe chronic obstructive pulmonary disease, severe arthritis, or peripheral vascular disease affecting ambulation).
• \. Had acute coronary syndrome or unstable angina within the past 3 months. 15. Has history of sustained ventricular tachycardia or aborted ventricular fibrillation.
• \. Has persistent elevation of systolic (˃180 mmHg) and diastolic (˃100 mmHg) blood pressure that is considered uncontrolled by physician.
• Has untreated hypo- or hyperthyroidism. 18-Prior or planned heart, liver, or other organ transplant. 19. Had a malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.

Sponsors & Collaborators

• Austin Neuromuscular Center: lead
• Alnylam Pharmaceuticals: collaborator

Study Sites (1)

Austin Neuromuscler Center/National Neuromuscular Research Institute

Austin, Texas, 78759, United States

Location

MeSH Terms

Conditions

Polyneuropathies; Amyloid Neuropathies, Familial; Amyloidosis, Hereditary, Transthyretin-Related

Interventions

patisiran

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Amyloid Neuropathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This protocol is a single center pilot study designed to evaluate the efficacy and safety of patisiran in adult patients with wtATTR amyloidosis and symptomatic polyneuropathy as assessed with Neuropathy Impairment Score (NIS).

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 27, 2021
• Study Start: August 3, 2022
• Primary Completion: April 1, 2026
• Study Completion: April 13, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

US (1)