Clinical trial NCT06672237: A Phase 3 Study of NTLA-2001 in ATTRv-PN
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Intellia Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2024-11-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a 1:1 ratio to nexiguran ziclumeran or placebo with opportunity for crossover.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Modified Neuropathy Impairment Score +7 (mNIS+7)
timeFrame: 18 Months
measure: Serum TTR
timeFrame: 29 Days
Secondary outcomes:
measure: Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire
timeFrame: 18 Months
measure: Modified Body Mass Index (mBMI)
timeFrame: 18 Months
measure: Serum TTR
timeFrame: 18 Months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital Británico de Buenos Aires
city: Westmead
country: Australia
facility: Westmead Hospital
city: Ribeirao Preto
country: Brazil
facility: HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)
city: Rio de Janeiro
country: Brazil
facility: Instituto de Educacao, Pesquisa e Gestao em Saude
city: Sao Paulo
country: Brazil
facility: PSEG Centro de Pesquisa Clinica S.A.
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Singapore
country: Singapore
facility: National University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou Branch
Study officials:
References: