Phase 1 Two-Part (Open-label, Single Ascending Dose (Part 1) and Open-label, Single Dose Expansion (Part 2)) 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)

Intellia Therapeutics4 sites in 4 countries72 target enrollmentStarted: November 5, 2020Last updated: January 30, 2026

Interventions

Drugs

Trial Snapshot

Phase: Phase 1
Status: Completed
Sponsor: Intellia Therapeutics
Enrollment: 72
Locations: 4
Primary Endpoint: Number of Participants with Treatment-Emergent Adverse Events

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials Related News

Study Overview

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)

Detailed Description

For ATTRv-PN 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 clinical measures of neuropathy and neurological function, and obtain additional safety data.

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.

Study Design

Study Type: Interventional
Allocation: Non Randomized
Intervention Model: Sequential
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to 90 Years (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

•Polyneuropathy Inclusion Criteria:
•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
•Polyneuropathy

Exclusion Criteria

•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:
•Doxycycline and/or tauroursodeoxycholic acid
•Any other investigational agent for the treatment of ATTRv-PN:
•Other protocol defined Inclusion/Exclusion criteria may apply
•Cardiomyopathy Inclusion Criteria (UK only):
•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.
•Cardiomyopathy Exclusion Criteria (UK only):
•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:
•Doxycycline and/or tauroursodeoxycholic acid
•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.
•Other protocol defined Inclusion/Exclusion criteria may apply

Arms & Interventions

Polyneuropathy Part 1: NTLA-2001

Experimental

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