Clinical Trial

Disease: Hereditary Transthyretin Amyloidosis, ATTR, (NCT04601051)

Disease info:

Transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of a protein called amyloid (amyloidosis) in the body's organs and tissues. These protein deposits most frequently occur in the peripheral nervous system, which is made up of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Protein deposits in these nerves result in a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system, which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by amyloidosis. In some cases, the brain and spinal cord (central nervous system) are affected. Other areas of amyloidosis include the heart, kidneys, eyes, and gastrointestinal tract. The age at which symptoms begin to develop varies widely among individuals with this condition, and is typically between ages 20 and 70.

There are three major forms of transthyretin amyloidosis, which are distinguished by their symptoms and the body systems they affect.

The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. The leptomeningeal form of transthyretin amyloidosis primarily affects the central nervous system. The cardiac form of transthyretin amyloidosis affects the heart.

Mutations in the TTR gene cause transthyretin amyloidosis. The TTR gene provides instructions for producing a protein called transthyretin. Transthyretin transports vitamin A (retinol) and a hormone called thyroxine throughout the body. To transport retinol and thyroxine, four transthyretin proteins must be attached (bound) to each other to form a four-protein unit (tetramer). Transthyretin is produced primarily in the liver. A small amount of this protein is produced in an area of the brain called the choroid plexus and in the light-sensitive tissue that lines the back of the eye (the retina).

TTR gene mutations are thought to alter the structure of transthyretin, impairing its ability to bind to other transthyretin proteins and altering its normal function.





The exact incidence of transthyretin amyloidosis is unknown. In northern Portugal, the incidence is thought to be one in 538 people. ATTR is less common among Americans of European descent, it is estimated to affect one in 100,000 people.
Official title:
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)

Trial Manager at Intellia, E-mail:










New Zealand, Auckland

United Kingdom, London

Umea, Sweden





Study start:
Oct. 19, 2020
74 participants
Gene editing method:
Type of edit:
Gene knock-out
Transthyretin (TTR)
Delivery method:
Lipid Nanoparticles (LNP) - In-vivo
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active recruiting


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).

This 2-part first in human (FIH) study consists of an open-label, single ascending dose Part 1, which may identify the optimal biologically active dose (OBD) of NTLA-2001, followed by Part 2, if applicable, an open-label, single-dose expansion at the OBD to further characterize activity of NTLA-2001, provide an initial assessment of the effect of NTLA-2001 on clinical measures of neuropathy and neurologic function, and obtain additional safety data at the OBD.

Biological: NTLA-2001

a clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration.

Experimental: Part 1: NTLA-2001

Participants, assigned to one of 4 dose-escalation cohorts, will receive a single dose of NTLA-2001 on Day 1 and will then be followed for up to 24 months.

Intervention: Biological: NTLA-2001

Experimental: Part 2:

Participants will receive the optimal biologically active dose (OBD) of NTLA-2001 identified in Part 1 as a single dose on Day 1 and will then be followed for up to 24 months.

Intervention: Biological: NTLA-2001

Last updated: Jul. 11, 2022
Source: United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA)
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