Neuromuscular DiseasePhase 3NCT06672237
A Phase 3 Study of NTLA-2001 in ATTRv-PN
A Phase 3 study testing nexiguran ziclumeran in people with Neuromuscular Disease and Neuromuscular Diseases (NMD), run by Intellia Therapeutics at 14 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Neuromuscular Disease, Neuromuscular Diseases (NMD), Neurodegenerative Disease
- What is being tested?
- nexiguran ziclumeran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 14 sitesin 6 countries
- Study dates
- 22 Nov 2024to Aug 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of ATTRv-PN
- Karnofsky Performance Status (KPS) ≥ 60
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
14 sites in 6 countries.
14 sites in 6 countries
Brazil4 sites
Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP)
Campinas
HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
Ribeirão Preto
Instituto de Educacao, Pesquisa e Gestao em Saude
Rio de Janeiro
PSEG Centro de Pesquisa Clinica S.A.
São Paulo
Argentina3 sites
Hospital Británico de Buenos Aires
Buenos Aires
Hospital Italiano de Buenos Aires (HIBA)
Buenos Aires
Hospital El Cruce
San Juan Bautista
Taiwan3 sites
National Taiwan University Hospital
Taipei
Taipei Veterans General Hospital
Taipei
Chang Gung Medical Foundation - Linkou Branch
Taoyuan
Singapore2 sites
National University Hospital
Singapore
Singapore General Hospital
Singapore
Mexico1 site
National Institute of Medical Sciences and Nutrition - Salvador Zubiran (INCMNSZ)
Tlalpan
About this study
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)
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.
Read the 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.
- Conditions
- Neuromuscular Disease, Neuromuscular Diseases (NMD), Neurodegenerative Disease, Neurodegenerative Disease, Hereditary, Neurodegenerative Diseases, Neuromuscular Diseases
- Being tested
- nexiguran ziclumeran, Normal Saline as Placebo
- 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
- Medical subject headings
- Neuromuscular Diseases, Neurodegenerative Diseases, Heredodegenerative Disorders, Nervous System, Nervous System Diseases, Genetic Diseases, Inborn, Amyloidosis, Familial, Amyloidosis, Polyneuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nexiguran ziclumeranBiological
Also called NTLA-2001
nexiguran ziclumeran 55 mg by single IV infusion
Normal Saline as PlaceboDrug
Normal saline (0.9% NaCl) by single IV infusion
| Study group | Role | What they receive |
|---|---|---|
| nexiguran ziclumeran | Experimental | nexiguran ziclumeran 55 mg by single IV infusion Receives: Biological: nexiguran ziclumeran |
| Normal Saline | Placebo comparator | Placebo; Normal saline (0.9% NaCl) by single IV infusion Receives: Drug: Normal Saline as Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Neuropathy Impairment Score +7 (mNIS+7)
Measured: 18 Months
Serum TTR
Measured: 29 Days
Secondary outcomes (3)
Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire
Measured: 18 Months
Modified Body Mass Index (mBMI)
Measured: 18 Months
Serum TTR
Measured: 18 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2024
- Study start22 Nov 2024
- Primary completionJul 2027 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuromuscular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 1:1 ratio to nexiguran ziclumeran or placebo with opportunity for crossover.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intellia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06672237
- Sponsor's protocol ID
- ITL-2001-CL-311
- Status last verified
- Oct 2026
- First submitted
- 1 Nov 2024
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06672237
- Acronym / sponsor ID
- ITL-2001-CL-311
- Conditions
- Neuromuscular Disease, Neuromuscular Diseases (NMD), Neurodegenerative Disease, Neurodegenerative Disease, Hereditary, Neurodegenerative Diseases, Neuromuscular Diseases
- Keywords
- TTR, Amyloidosis, Polyneuropathy, NTLA-2001, ATTR, ATTR-PN, ATTRv-PN, Transthyretin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Intellia TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 22 Nov 2024 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 4 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized in a 1:1 ratio to nexiguran ziclumeran or placebo with opportunity for crossover.
| Arm | Type | Receives |
|---|---|---|
| nexiguran ziclumeran | Experimental | Biological: nexiguran ziclumerannexiguran ziclumeran 55 mg by single IV infusion |
| Normal Saline | Placebo comparator | Drug: Normal Saline as PlaceboPlacebo; Normal saline (0.9% NaCl) by single IV infusion |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosis of ATTRv-PN
- Karnofsky Performance Status (KPS) ≥ 60
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nexiguran ziclumeranAlso: NTLA-2001nexiguran ziclumeran 55 mg by single IV infusion | Biological | nexiguran ziclumeran |
| Normal Saline as PlaceboNormal saline (0.9% NaCl) by single IV infusion | Drug | Normal Saline |
Primary outcome
Modified Neuropathy Impairment Score +7 (mNIS+7)
Time frame: 18 Months
Serum TTR
Time frame: 29 Days
3 secondary outcomes
Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire
Time frame: 18 Months
Modified Body Mass Index (mBMI)
Time frame: 18 Months
Serum TTR
Time frame: 18 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing nexiguran ziclumeran in people with Neuromuscular Disease and Neuromuscular Diseases (NMD), run by Intellia Therapeutics at 14 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Brazil, Argentina, Taiwan, Singapore, Mexico and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Neuropathy Impairment Score +7 (mNIS+7) (time frame: 18 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.