NTLA-2001

NTLA-2001 is an experimental therapy that could potentially be the first curative treatment for ATTR amyloidosis.

CRISPR/cas9 technology is a novel gene editing tool that allows scientists to alter genes very precisely and efficiently. The protein Cas9 (or CRISPR- associated) is an enzyme that functions like a pair of molecular scissors, so that specific sections of the DNA can be removed, altered or added.

NTLA-2001 is the first CRISPR therapy to be administered systemically (intravenously) to edit genes inside the body. Almost all the TTR in the body is made in the liver. NTLA-2001 uses a lipid nanoparticle delivery system to deliver the gene editing CRISPR protein to the liver.

The goal is to permanently delete the gene for TTR in a single course of treatment.

If this process happens in enough cells, it may lead to a potentially significant decrease in TTR protein production and thus, an impact on disease. Preclinical data has shown promising results, and this trial is the first time the therapy has been administered to humans.

The trial

This is a phase 1, first in human (FIH), open-label trial to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2001 in patients with hereditary ATTR amyloidosis with polyneuropathy and patients with ATTR amyloidosis and cardiomyopathy.

What the study involves for patients

In part 1 of the study, participants will receive a single dose of NTLA-2001 and then be followed for up to 24 months. In part 2, participants will receive the optimal biologically active dose (OBD) identified in part 1 as a single dose and then be followed for up to 24 months.

Who can take part in the trial?

Patients diagnosed with hereditary ATTR amyloidosis and polyneuropathy or ATTR amyloid cardiomyopathy may take part. Patients may not take part in the study if they have non-ATTR amyloidosis, leptomeningeal TTR amyloidosis, or have used a different TTR-directed therapy for ATTR amyloidosis within a certain prior timeframe. 

For a full list of inclusion and exclusion criteria, see the clinicaltrials.gov website. Recruitment of about 38 participants is planned.

Recruitment of 38 participants is planned.

Outcomes

The primary outcomes assessed will include pharmacokinetic and pharmacodynamic parameters reflecting efficacy of the therapy and adverse events. 

Other outcomes assessed will include clinical assessments of polyneuropathy-related symptoms and cardiomyopathy.

Timing

This study is open for recruitment at the NAC.