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)

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.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Amyloidosis; Metabolism, Inborn Errors; Polyneuropathies; Amyloid Neuropathies; Amyloid Neuropathies, Familial; Amyloidosis, Familial; Peripheral Nervous System Disease; Neuromuscular Disease; Amyloidosis, Hereditary; Neurodegenerative Disease, Hereditary; Nervous System Disease; Neurodegenerative Disease; Genetic Disease, Inborn; Nerve Disorders; Neuromuscular Diseases (NMD)
• Intervention / Treatment: Biological: nexiguran ziclumeran; Drug: Normal Saline as Placebo

Detailed Description

This is a multinational, multicenter, double-blind, placebo-controlled study in approximately 60 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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Manager at Intellia; Phone Number: 6 1-857-285-6200; Email: medicalinformation@intelliatx.com

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Recruiting
    • Hospital Britanico de Buenos Aires
  • Buenos Aires, Argentina
    • Recruiting
    • Hospital Italiano de Buenos Aires (HIBA)
  • San Juan Bautista, Argentina
    • Recruiting
    • Hospital El Cruce
• Brazil
  • Campinas, Brazil
    • Recruiting
    • Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)
  • Ribeirão Preto, Brazil
    • Recruiting
    • HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
  • Rio de Janeiro, Brazil
    • Recruiting
    • Instituto de Educação, Pesquisa e Gestão em Saúde
  • São Paulo, Brazil
    • Recruiting
    • PSEG Centro de Pesquisa Clinica S.A.
• Mexico
  • Tlalpan, Mexico
    • Recruiting
    • National Institute of Medical Sciences and Nutrition - Salvador Zubiran (INCMNSZ)
• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Hospital
  • Singapore, Singapore
    • Recruiting
    • Singapore General Hospital
• Taiwan
  • Taipei, Taiwan
    • Active, not recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Active, not recruiting
    • Taipei Veterans General Hospital
  • Taoyuan District, Taiwan
    • Active, not recruiting
    • Chang Gung Medical Foundation - Linkou Branch
• Thailand
  • Bangkok, Thailand
    • Recruiting
    • Siriraj Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• History of liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nexiguran ziclumeran; nexiguran ziclumeran 55 mg by single IV infusion	Biological: nexiguran ziclumeran; nexiguran ziclumeran 55 mg by single IV infusion; Other Names: NTLA-2001
Placebo Comparator: Normal Saline; Placebo; Normal saline (0.9% NaCl) by single IV infusion	Drug: Normal Saline as Placebo; Normal saline (0.9% NaCl) by single IV infusion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Intellia Therapeutics
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: November 1, 2024
• First Submitted That Met QC Criteria: November 1, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: TTR; Amyloidosis; Polyneuropathy; ATTR; Transthyretin; CRISPR; TTR-mediated amyloidosis; ATTR-PN; Amyloidosis, hereditary; NTLA-2001; ATTRv-PN; Amyloidosis, hereditary, transthyretin-related amyloidosis; Transthretin amyloid polyneuropathy; TTR PN; TTR polyneuropathy; nexiguran ziclumeran; nex-z
• Additional Relevant MeSH Terms: Proteostasis Deficiencies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Polyneuropathies; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Metabolic Diseases; Amyloidosis; Metabolism, Inborn Errors; Neuromuscular Diseases; Amyloid Neuropathies; Amyloid Neuropathies, Familial; Heredodegenerative Disorders, Nervous System; Amyloidosis, Familial; Amyloidosis, Hereditary, Transthyretin-Related; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution; NTLA-2001
• Other Study ID Numbers: ITL-2001-CL-311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes