NCT04601051

Brief Summary

This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NTLA-2001 in participants with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and participants with hereditary transthyretin amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM)

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
72

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2020

Longer than P75 for phase_1

Geographic Reach
4 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 19, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 23, 2020

Completed
13 days until next milestone

Study Start

First participant enrolled

November 5, 2020

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 12, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 12, 2025

Completed
Last Updated

January 30, 2026

Status Verified

January 1, 2026

Enrollment Period

4.9 years

First QC Date

October 19, 2020

Last Update Submit

January 28, 2026

Conditions

Transthyretin-Related (ATTR) Familial Amyloid PolyneuropathyTransthyretin-Related (ATTR) Familial Amyloid CardiomyopathyWild-Type Transthyretin Cardiac Amyloidosis

Keywords

NTLA-2001PharmacokineticsPharmacodynamicsNeurologic FunctionClustered Regularly Interspaced Short Palindromic RepeatsCRISPRPolyneuropathyATTRTransthyretinTTRAmyloidosisFamilial Amyloid PolyneuropathyFAPCardiomyopathy

Outcome Measures

Primary Outcomes (13)

  • Number of Participants with Treatment-Emergent Adverse Events

    up to Day 730

  • Number of Participants with Clinically Significant Clinical Laboratory Test Findings

    up to Day 730

  • Number of Participants with Clinically Significant Safety Measurements

    up to Day 730

  • Percent Change from Baseline in Serum TTR (enzyme-linked immunosorbent assay [ELISA])

    up to Day 730

  • Percent Change from Baseline in Serum Prealbumin

    up to Day 730

  • Mean Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

    up to Day 730

  • Mean Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUCinf) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

    up to Day 730

  • Mean Maximum Concentration (Cmax) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

    up to Day 730

  • Mean Time of the Maximum Concentration (Tmax) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

    up to Day 730

  • Mean Terminal Half-Life (t½) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

    up to Day 730

  • Mean Apparent Clearance (CL) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

    up to Day 730

  • Mean Volume of Distribution (Vd) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

    up to Day 730

  • Change from Baseline in Anti-Drug Antibody to NTLA-2001 and Anti-Cas9 Protein Antibody to Transgene Product Levels

    up to Day 730

Secondary Outcomes (16)

  • Polyneuropathy only: Change from Baseline in Familial Amyloid Polyneuropathy (FAP) Stage.

    up to Day 730

  • Polyneuropathy only: Change from Baseline in Polyneuropathy Disability (PND) Score

    up to Day 730

  • Polyneuropathy only: Change from Baseline in Modified Body Mass Index (mBMI)

    up to Day 730

  • Polyneuropathy only: Change from Screening in Neuropathy Impairment Score (NIS)

    up to Day 730

  • Polyneuropathy only: Change from Baseline in Modified Neuropathy Impairment Score +7 (mNIS+7)

    up to Day 730

  • +11 more secondary outcomes

Study Arms (5)

Polyneuropathy Part 1: NTLA-2001

EXPERIMENTAL

Participants, assigned to one of 4 dose-escalation cohorts, will receive a single dose of NTLA-2001.

Biological: NTLA-2001

Polyneuropathy Part 2: NTLA-2001

EXPERIMENTAL

Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.

Biological: NTLA-2001

Cardiomyopathy Part 1 (UK only): NTLA-2001

EXPERIMENTAL

Participants, assigned to one of 2 dose-escalation cohorts, will receive a single dose of NTLA-2001.

Biological: NTLA-2001

Cardiomyopathy Part 2 (UK only): NTLA-2001

EXPERIMENTAL

Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.

Biological: NTLA-2001

Polyneuropathy Follow-on Dosing (PN Part 1 Dose Level 1 Subjects only): NTLA-2001

EXPERIMENTAL

Participants assigned to the follow-on dosing cohort will receive a subsequent dose of NTLA-2001.

Biological: NTLA-2001

Interventions

NTLA-2001BIOLOGICAL

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-2001Cardiomyopathy Part 2 (UK only): NTLA-2001Polyneuropathy Follow-on Dosing (PN Part 1 Dose Level 1 Subjects only): NTLA-2001Polyneuropathy Part 1: NTLA-2001Polyneuropathy Part 2: NTLA-2001

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male and/or female participants 18 to 80 years of age inclusive, at the time of signing the informed consent
  • 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

You may not qualify if:

  • 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 timeframe:
  • Patisiran
  • Inotersen
  • Vutrisiran
  • Tafamidis
  • Diflunisal
  • Doxycycline and/or tauroursodeoxycholic acid
  • Any other investigational agent for the treatment of 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.
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Clinical Trial Site

Paris, France

Location

Clinical Trial Site

Auckland, New Zealand

Location

Clinical Trial Site

Umeå, Sweden

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (4)

  • 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.

    PMID: 41002250DERIVED

  • 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.

    PMID: 39555828DERIVED

  • 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.

    PMID: 34215024DERIVED

  • 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.

    PMID: 34175043DERIVED

MeSH Terms

Conditions

Amyloid Neuropathies, FamilialPolyneuropathiesAmyloidosisCardiomyopathies

Interventions

NTLA-2001

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesNervous System DiseasesAmyloid NeuropathiesPeripheral Nervous System DiseasesNeuromuscular DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesAmyloidosis, FamilialMetabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic DiseasesProteostasis DeficienciesHeart DiseasesCardiovascular Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 19, 2020

First Posted

October 23, 2020

Study Start

November 5, 2020

Primary Completion

September 12, 2025

Study Completion

September 12, 2025

Last Updated

January 30, 2026

Record last verified: 2026-01

Locations

SE(1)NZ(1)FR(1)GB(1)