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

NCT06672237 — Phase 3, Recruiting, 60 participants, Intellia Therapeutics

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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)

Registry	NCT06672237
Status	Recruiting
Phase	Phase 3
Study type	Interventional; randomized, parallel, masking: quadruple, treatment
Enrollment	60 (Estimated)
Sponsor	Intellia Therapeutics (Industry); collaborators: Regeneron Pharmaceuticals
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
Interventions	nexiguran ziclumeran, Normal Saline as Placebo (Biological, drug)
Dates	start 2024-11-22, primary completion 2027-07-01 (estimated), completion 2028-08-01 (estimated), first posted 2024-11-04, last updated 2026-04-16
Locations	14 sites in Argentina, Brazil, Mexico, Singapore, Taiwan, Thailand

-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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
nexiguran ziclumeran	Experimental	Biological: nexiguran ziclumeran	nexiguran ziclumeran 55 mg by single IV infusion
Normal Saline	Placebo comparator	Drug: Normal Saline as Placebo	Placebo; Normal saline (0.9% NaCl) by single IV infusion

nexiguran ziclumeran (Biological), also known as NTLA-2001: nexiguran ziclumeran 55 mg by single IV infusion
Normal Saline as Placebo (Drug): Normal saline (0.9% NaCl) by single IV infusion

+Outcome measures

Primary outcomes

Modified Neuropathy Impairment Score +7 (mNIS+7) [18 Months]
Serum TTR [29 Days]

Secondary outcomes

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

+Eligibility

Sex: All, ages: 18 Years to 85 Years

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

+Locations (14)

Facility	City	Country	Status
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	Taiwan	Active not recruiting
Siriraj Hospital	Bangkok	Thailand	Recruiting