A Phase 3 Study of NTLA-2001 in ATTRv-PN

MAGNITUDE-2: A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN)

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06672237

Enrollment

Registered

2024-11-04

Start date

2024-11-22

Completion date

2028-08-31

Last updated

2025-11-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neuromuscular Disease, Neuromuscular Diseases (NMD), Neurodegenerative Disease, Neurodegenerative Disease, Hereditary, Neurodegenerative Diseases, Neuromuscular Diseases, Nerve Disorders, Nervous System Disease, Nervous System Diseases, Genetic Disease, Inborn, Amyloidosis, Familial, Amyloidosis, Hereditary, Amyloidosis, Polyneuropathies, Amyloid Neuropathies, Amyloid Neuropathies, Familial, Peripheral Nervous System Disease, Peripheral Nervous System Diseases, Metabolism, Inborn Errors, Metabolic Diseases

Keywords

TTR, Amyloidosis, Polyneuropathy, NTLA-2001, ATTR, ATTR-PN, ATTRv-PN, Transthyretin, TTR-mediated amyloidosis, Amyloidosis, hereditary, Amyloidosis, hereditary, transthyretin-related amyloidosis, Transthretin amyloid polyneuropathy, TTR PN, TTR polyneuropathy, nexiguran ziclumeran, nex-z

Brief summary

This study will be conducted to evaluate the efficacy and safety of a single dose of nexiguran ziclumeran (NTLA-2001) compared to placebo in participants with ATTRv-PN.

Detailed description

This is a multinational, multicenter, double-blind, placebo-controlled study in approximately 50 participants, who will be randomized 1:1 to receive a single infusion of either nexiguran ziclumeran or placebo. To ensure all participants will have the potential to receive nexiguran ziclumeran, participants will have the option to cross over to the opposite study arm at Month 12 or Month 18, depending on study criteria.

Interventions

BIOLOGICALnexiguran ziclumeran

nexiguran ziclumeran 55 mg by single IV infusion

DRUGNormal Saline as Placebo

Normal saline (0.9% NaCl) by single IV infusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

Participants will be randomized in a 1:1 ratio to nexiguran ziclumeran or placebo with opportunity for crossover.

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of ATTRv-PN * Karnofsky Performance Status (KPS) ≥ 60

Exclusion criteria

* Other causes of amyloidosis (amyloidosis caused by non-TTR protein) * Other known causes of sensorimotor or autonomic neuropathy * Diabetes mellitus * New York Heart Association Class III or IV heart failure * Liver failure * Hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection * Prior receipt of a TTR silencer (Small interfering RNA (siRNA) or Antisense oligonucleotides (ASOs)) * Estimated Glomerular Filtration Rate \< 30 mL/min/1.73 m2 * Unable or unwilling to take vitamin A supplementation for the duration of the study

Design outcomes

Primary

Measure	Time frame
Modified Neuropathy Impairment Score +7 (mNIS+7)	18 Months
Serum TTR	29 Days

Secondary

Measure	Time frame
Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire	18 Months
Modified Body Mass Index (mBMI)	18 Months
Serum TTR	18 Months

Countries

Argentina, Australia, Brazil, Mexico, New Zealand, Singapore, Taiwan, Thailand

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026