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

NCT06672237 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: ITL-2001-CL-311
• Study Type: interventional
• Target: 60
• Locations: 6 countries
• Sites: 14

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.

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; CRISPR

Outcome Measures

Primary Outcomes (2)

• Modified Neuropathy Impairment Score +7 (mNIS+7)

  18 Months

• Serum TTR

  29 Days

Secondary Outcomes (3)

• Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire

  18 Months

• Modified Body Mass Index (mBMI)

  18 Months

• Serum TTR

  18 Months

Study Arms (2)

nexiguran ziclumeran

EXPERIMENTAL

nexiguran ziclumeran 55 mg by single IV infusion

Biological: nexiguran ziclumeran

Normal Saline

PLACEBO COMPARATOR

Placebo; Normal saline (0.9% NaCl) by single IV infusion

Drug: Normal Saline as Placebo

Interventions

nexiguran ziclumeran BIOLOGICAL

nexiguran ziclumeran 55 mg by single IV infusion

Also known as: NTLA-2001

nexiguran ziclumeran

Normal Saline as Placebo DRUG

Normal saline (0.9% NaCl) by single IV infusion

Normal Saline

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Intellia Therapeutics: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (14)

Hospital Británico de Buenos Aires

Buenos Aires, Argentina

RECRUITING

Hospital Italiano de Buenos Aires (HIBA)

Buenos Aires, Argentina

RECRUITING

Hospital El Cruce

San Juan Bautista, Argentina

RECRUITING

Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)

Campinas, Brazil

RECRUITING

HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto

Ribeirão Preto, Brazil

RECRUITING

Instituto de Educacao, Pesquisa e Gestao em Saude

Rio de Janeiro, Brazil

RECRUITING

PSEG Centro de Pesquisa Clinica S.A.

São Paulo, Brazil

RECRUITING

National Institute of Medical Sciences and Nutrition - Salvador Zubiran (INCMNSZ)

Tlalpan, Mexico

RECRUITING

National University Hospital

Singapore, Singapore

RECRUITING

Singapore General Hospital

Singapore, Singapore

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

ACTIVE NOT RECRUITING

Taipei Veterans General Hospital

Taipei, Taiwan

ACTIVE NOT RECRUITING

Chang Gung Medical Foundation - Linkou Branch

Taoyuan District, Taiwan

ACTIVE NOT RECRUITING

Siriraj Hospital

Bangkok, Thailand

RECRUITING

MeSH Terms

Conditions

Neuromuscular Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Nervous System Diseases; Genetic Diseases, Inborn; Amyloidosis, Familial; Amyloidosis; Polyneuropathies; Amyloid Neuropathies; Amyloid Neuropathies, Familial; Peripheral Nervous System Diseases; Metabolism, Inborn Errors; Metabolic Diseases; Amyloidosis, Hereditary, Transthyretin-Related

Interventions

NTLA-2001; Saline Solution

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Proteostasis Deficiencies

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Trial Manager at Intellia

CONTACT

1-857-285-6200; medicalinformation@intelliatx.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: November 1, 2024
• First Posted: November 4, 2024
• Study Start: November 22, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AR (3); BR (4); SG (2); TH (1); TW (3); ME (1)