Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)
NCT ID: NCT04601051
Last Updated: 2025-05-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
72 participants
INTERVENTIONAL
2020-11-05
2026-08-31
Brief Summary
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Detailed Description
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For ATTR-CM participants, Part 1 consists of an open-label, single-ascending dose study, which identifies the dose for evaluation in the cohort expansion of Part 2. Part 2 will follow as an open-label, dose expansion study to further characterize the activity of NTLA-2001, provide an initial assessment of the effect of NTLA-2001 on cardiac measures, and obtain additional safety data.
All participants who are dosed with NTLA-2001 will be offered to participate in a long-term safety monitoring follow-up study via a separate protocol.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Polyneuropathy Part 1: NTLA-2001
Participants, assigned to one of 4 dose-escalation cohorts, will receive a single dose of NTLA-2001.
NTLA-2001
A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration
Polyneuropathy Part 2: NTLA-2001
Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.
NTLA-2001
A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration
Cardiomyopathy Part 1 (UK only): NTLA-2001
Participants, assigned to one of 2 dose-escalation cohorts, will receive a single dose of NTLA-2001.
NTLA-2001
A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration
Cardiomyopathy Part 2 (UK only): NTLA-2001
Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.
NTLA-2001
A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration
Polyneuropathy Follow-on Dosing (PN Part 1 Dose Level 1 Subjects only): NTLA-2001
Participants assigned to the follow-on dosing cohort will receive a subsequent dose of NTLA-2001.
NTLA-2001
A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration
Interventions
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NTLA-2001
A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration
Eligibility Criteria
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Inclusion Criteria
* Diagnosis of polyneuropathy (PN) due to transthyretin (TTR) amyloidosis (ATTR)
* Must have a body weight of at least 45 kilograms (kg) at Screening visit
* Lack of access to approved treatments for ATTR and/or progression of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) despite use of approved treatment for ATTRv-PN
* Male and/or female participants 18 to 90 years of age inclusive, at the time of signing the informed consent
* Diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as hereditary ATTR amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM).
* Must have a body weight of at least 45 kilograms (kg) at Screening visit
* New York Heart Association (NYHA) Class I-III heart failure
* At least 1 prior hospitalization for heart failure and/or clinical evidence of heart failure.
* Able to complete ≥150 meters on the 6-minute walk test (6-MWT) during the Screening period.
Exclusion Criteria
* Known leptomeningeal transthyretin amyloidosis
* Use of any of the following TTR-directed therapy for ATTR within certain timeframe:
1. Patisiran
2. Inotersen
3. Vutrisiran
4. Tafamidis
5. Diflunisal
6. Doxycycline and/or tauroursodeoxycholic acid
7. Any other investigational agent for the treatment of ATTRv-PN:
* Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL) amyloidosis
* Known leptomeningeal transthyretin amyloidosis
* Use of any of the following TTR-directed therapy for ATTR within certain timeframes:
1. Patisiran
2. Inotersen
3. Vutrisiran
4. Tafamidis
5. Diflunisal
6. Doxycycline and/or tauroursodeoxycholic acid
7. Investigational TTR stabilizer (e.g., AG-10)
* Participants with heart failure that in the opinion of the investigator is caused by ischemic heart disease, hypertension, or uncorrected valvular disease and not primarily due to transthyretin amyloid cardiomyopathy.
* Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker is indicated but will not be placed. Pacemaker or defibrillator placement, initiation of or change in anti-arrhythmic medication within 28 days prior to study drug administration.
18 Years
90 Years
ALL
No
Sponsors
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Intellia Therapeutics
INDUSTRY
Responsible Party
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Locations
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Clinical Trial Site
Paris, , France
Clinical Trial Site
Auckland, , New Zealand
Clinical Trial Site
Umeå, , Sweden
Clinical Trial Site
London, , United Kingdom
Countries
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References
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Gillmore JD, Gane E, Taubel J, Pilebro B, Echaniz-Laguna A, Kao J, Litchy W, Shahda S, Haagensen A, Walsh L, Smith D, Kachadourian J, Ward JH, Lebwohl D, Zhu P, Xu Y, Leung A, Sonderfan A, Gutstein DE, Manvelian G, Adams D. Nexiguran Ziclumeran Gene Editing in Hereditary ATTR with Polyneuropathy. N Engl J Med. 2025 Oct 9;393(14):1375-1386. doi: 10.1056/NEJMoa2510209. Epub 2025 Sep 25.
Fontana M, Solomon SD, Kachadourian J, Walsh L, Rocha R, Lebwohl D, Smith D, Taubel J, Gane EJ, Pilebro B, Adams D, Razvi Y, Olbertz J, Haagensen A, Zhu P, Xu Y, Leung A, Sonderfan A, Gutstein DE, Gillmore JD. CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy. N Engl J Med. 2024 Dec 12;391(23):2231-2241. doi: 10.1056/NEJMoa2412309. Epub 2024 Nov 16.
Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, Seitzer J, O'Connell D, Walsh KR, Wood K, Phillips J, Xu Y, Amaral A, Boyd AP, Cehelsky JE, McKee MD, Schiermeier A, Harari O, Murphy A, Kyratsous CA, Zambrowicz B, Soltys R, Gutstein DE, Leonard J, Sepp-Lorenzino L, Lebwohl D. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med. 2021 Aug 5;385(6):493-502. doi: 10.1056/NEJMoa2107454. Epub 2021 Jun 26.
Stephenson AA, Flanigan KM. Gene editing and modulation for Duchenne muscular dystrophy. Prog Mol Biol Transl Sci. 2021;182:225-255. doi: 10.1016/bs.pmbts.2021.01.029. Epub 2021 Mar 3.
Other Identifiers
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2020-002034-32
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ITL-2001-CL-001
Identifier Type: -
Identifier Source: org_study_id
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