Clinical Trial

Disease: 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.

 

 

 

Frequency:
Although the exact incidence of transthyretin amyloidosis is unknown, hereditary ATTR amyloidosis (hATTR) is estimated to affect over 10,000 individuals globally.. In northern Portugal, the incidence is thought to be one in 538 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)
Who:

Contact

Trial Manager at Intellia

Phone: 833-888-0387

Email: clinicalscience@intelliatx.com

 

 

 

 

Sponsor:
Partners:

 

 

 

Locations:

France

Clinical Trial Site, Paris, France

 

New Zealand

Clinical Trial Site, Auckland, New Zealand

 

Sweden

Clinical Trial Site, Umea, Sweden

 

United Kingdom

Clinical Trial Site, London, United Kingdom

 

Study start:
Nov. 5, 2020
Enrollment:
72 participants
Gene editing method:
CRISPR-Cas9
Type of edit:
Gene knock-out
Gene:
Transthyretin (TTR)
Delivery method:
Lipid Nanoparticles (LNP) - In-vivo
Safety updates:

(18-10-2023) Intellia Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application to Initiate a Pivotal Phase 3 Trial of NTLA-2001 for the Treatment of Transthyretin (ATTR) Amyloidosis with Cardiomyopathy

(02-11-2023) Intellia Presents New Interim Data from the Ongoing Phase 1 Study of NTLA-2001 at the 4th International ATTR Amyloidosis Meeting

(28-02-2022) Intellia and Regeneron Announce Updated Phase 1 Data Demonstrating a Single Dose of NTLA-2001, an Investigational CRISPR Therapy for Transthyretin (ATTR) Amyloidosis, Resulted in Rapid, Deep and Sustained Reduction in Disease-Causing Protein

(22-11-2021) Intellia Therapeutics Announces Expansion of Ongoing Phase 1 Study of NTLA-2001 to Include Adults with Transthyretin Amyloidosis with Cardiomyopathy (ATTR-CM)

(21-10-2021) Intellia Therapeutics Receives U.S. FDA Orphan Drug Designation for NTLA-2001, an Investigational CRISPR Therapy for the Treatment of Transthyretin (ATTR) Amyloidosis

(26-06-2021) Intellia and Regeneron Announce Landmark Clinical Data Showing Deep Reduction in Disease-Causing Protein After Single Infusion of NTLA-2001, an Investigational CRISPR Therapy for Transthyretin (ATTR) Amyloidosis

(30-03-2021) Intellia Therapeutics’ Investigational CRISPR Treatment NTLA-2001 Receives European Union Orphan Drug Designation for ATTR Amyloidosis

(19-10-2020) Intellia Therapeutics Receives Authorization to Initiate Phase 1 Clinical Trial of NTLA-2001 for Transthyretin Amyloidosis (ATTR)

 

 

 

 

Indicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active not recruiting

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.

Last updated: Dec. 28, 2023
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