Trial | NCT04601051  Report issue

Title

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)
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)

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Active, not recruiting

  • Study Participants

    72
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)
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 Started
Nov 05
2020
Primary Completion
Aug 31
2025
Anticipated
Study Completion
Aug 31
2026
Anticipated
Last Update
Sep 08
2023

Biological 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 1: NTLA-2001 Experimental

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

Polyneuropathy Part 2: NTLA-2001 Experimental

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

Cardiomyopathy Part 2 (UK only): NTLA-2001 Experimental

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

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:

Patisiran
Inotersen
Vutrisiran
Tafamidis
Diflunisal
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:

Patisiran
Inotersen
Vutrisiran
Tafamidis
Diflunisal
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
No Results Posted