Not recruitingRare disease

Study on NTLA-2001 for Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy

Fast replyInvestigationalNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a condition called Hereditary Transthyretin Amyloidosis with Polyneuropathy (ATTRv-PN) and another condition known as Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM). These are diseases where abnormal proteins build up in the body, affecting nerves and the heart. The treatment being tested is called NTLA-2001, which is a new type of therapy that uses a technology called CRISPR/Cas9 to edit genes. This treatment involves a special messenger RNA that helps guide the editing process to target the TTR gene, which is responsible for the disease.

The purpose of the study is to evaluate the safety and how well the body tolerates NTLA-2001, as well as to understand how the drug moves through and affects the body. The study is divided into two parts. In the first part, patients will receive a single dose of the treatment to see how they respond. In the second part, the study will expand to include more patients to further assess the treatment's effects. Some patients who have already received a smaller dose of NTLA-2001 may receive a follow-up dose to gather more information.

Throughout the study, various assessments will be conducted to monitor the safety of the treatment and its impact on the patients' conditions. These assessments will include checking for any immune reactions, measuring how the drug is processed in the body, and evaluating changes in the symptoms of polyneuropathy, which is a condition where multiple nerves are damaged. The study aims to provide valuable insights into the potential of NTLA-2001 as a treatment for these challenging diseases.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial Infusion
Receive an infusion of NTLA-2001, a solution designed to target the human TTR gene. This is administered as a dispersion for infusion.
The dosage is determined based on the study phase: a single ascending dose in Part 1 or a single dose expansion in Part 2.
Step 2
Monitoring and Assessments
Undergo safety assessments to monitor any potential side effects or reactions to the treatment.
Participate in pharmacokinetic assessments to understand how the drug is processed in the body.
Participate in pharmacodynamic assessments to evaluate the drug's effects on the body.
Step 3
Follow-up Visits
Attend scheduled follow-up visits for continued monitoring of health and response to the treatment.
These visits include polyneuropathy assessments to evaluate the condition of the peripheral nerves.
Step 4
Follow-on Dosing Sub-study (if applicable)
For those who previously received a 0.1 mg/kg dose of NTLA-2001, a follow-on dosing sub-study may be conducted.
This involves receiving a 55 mg dose to further evaluate safety and effects.

Who can join the trial?

20 criteria

Participants must be men or women aged 18 to 80 years old.
Participants must have a diagnosis of **Polyneuropathy (PN)** due to **Transthyretin Amyloidosis (ATTR)**, which includes:
- A documented **TTR mutation**, meaning a change in the TTR gene.
- A clinical diagnosis of **sensorimotor peripheral neuropathy**, which affects the nerves that control movement and sensation.
- A **Neuropathy Impairment Score (NIS)** between 5 and 130 during the screening process. This score measures nerve damage.
- A **Polyneuropathy Disability (PND) score** of 3b or less, which assesses the level of disability caused by nerve damage.
- Participants must weigh at least 45 kg (about 99 pounds) at the screening visit.
- Participants must meet certain laboratory test criteria during screening, including:
  - Normal levels of liver enzymes (AST and ALT), bilirubin, and blood clotting tests (INR).
  - For those with **Gilbert’s Syndrome**, bilirubin levels can be up to twice the normal limit.
  - An **estimated glomerular filtration rate (eGFR)** greater than 45 mL/min/1.73m², which measures kidney function.
  - A **platelet count** of at least 100,000 cells/mm³, which is important for blood clotting.
  - Normal or clinically acceptable levels of blood clotting factors (aPTT, PT, fibrinogen, and D-dimer).
  - A **NT proBNP** level less than 2,000 pg/mL, which is a marker of heart stress.
  - **LDL cholesterol** levels below 200 mg/dL, with or without medication.
  - **Vitamin A** levels at or above the lower normal limit.
  - Normal **thyroid-stimulating hormone (TSH)** levels.
  - Participants must agree to limit alcohol consumption to one drink per day during screening and for 28 days after treatment.
  - Participants must either lack access to approved treatments for ATTRv PN or have worsening symptoms despite treatment. This includes:
    
    No approved therapy available in their region.
    Inability to receive approved treatment due to intolerance, medical reasons, financial reasons, or other reasons.
    Worsening symptoms despite treatment for at least 6 months, shown by increased PND or NIS scores, decreased body-mass index, or changes in walking tests.
    Female participants must be postmenopausal or surgically sterile.

Who cannot join the trial?

4 criteria

Patients who have a different condition than Hereditary Transthyretin Amyloidosis with Polyneuropathy (ATTRv-PN) cannot participate. This is a specific genetic condition affecting nerves.
Patients who are not within the specified age range for the study cannot participate. The study has specific age requirements.
Patients who are part of a vulnerable population, meaning they might need special protection or care, are not eligible.
Patients who have not previously received a specific dose of the study medication, NTLA-2001, may not be eligible for certain parts of the study.

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Verified sites

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Hopital Beaujon
Verified
Clichy, France
Region Vaesterbotten
Responsive
Umea, Sweden

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Investigated drugs

NTLA-2001 is an experimental medication being studied for its potential to treat hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and transthyretin amyloidosis-related cardiomyopathy (ATTR-CM). This medication is designed to target and reduce the production of abnormal transthyretin protein, which is responsible for the symptoms of these conditions. The study aims to assess the safety and how the body processes and responds to NTLA-2001.

What is already known about the treatment

NTLA-2001 – NTLA-2001 is administered through an intravenous infusion, designed to treat Hereditary Transthyretin Amyloidosis with Polyneuropathy (ATTRv-PN). Currently, it is in the clinical trial phase, specifically a Phase 1 study, to assess its safety, tolerability, and how it behaves in the body. The main therapeutic indication is for patients suffering from ATTRv-PN, a condition characterized by the buildup of abnormal proteins in the body. At the molecular level, NTLA-2001 works by using CRISPR technology to edit the genes responsible for producing the faulty transthyretin protein, aiming to reduce its production. It falls under the pharmacological classification of gene-editing therapies.

Investigated diseases

Hereditary Transthyretin Amyloidosis with Polyneuropathy (ATTRv-PN) – This is a genetic disorder characterized by the buildup of abnormal protein deposits called amyloid in the body's tissues and organs. The condition primarily affects the peripheral nerves, leading to symptoms such as numbness, tingling, and pain in the hands and feet. Over time, the disease can progress to cause muscle weakness and loss of reflexes. As the amyloid deposits accumulate, they can also affect other organs, including the heart and kidneys. The progression of symptoms can vary widely among individuals, with some experiencing rapid deterioration while others have a slower course. The disease is inherited in an autosomal dominant pattern, meaning a single copy of the altered gene in each cell is sufficient to cause the disorder.