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siRNA therapy clinical trial for Parkinson’s

This clinical trial is testing an siRNA therapy for Parkinson’s disease.

The siRNA (small interfering RNA) therapy is designed to lower the levels of α-synuclein, a protein linked to the progression of Parkinson’s. By reducing the levels of this protein, researchers hope to slow the progression of the disease.

The clinical trial will assess the effects of the siRNA therapy on the body, how the body processes it, and the best dose level.

How do I take part?

If you are interested in taking part in this clinical trial, email Jim Howley, Global Lead Patient Advocacy and Engagement, at Prevail.Patients@lilly.com or speak to your healthcare team.

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Who can take part?

To join the Parkinson’s siRNA (small interfering RNA) therapy clinical trial, you need to meet these requirements:

  • Aged between 30 and 80 years old.
  • Have a diagnosis of Parkinson’s.
  • If you take medication for your Parkinson’s, your dose should be stable for at least eight weeks before receiving the clinical trial treatment.
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What is siRNA therapy?

siRNA (small interfering RNA) is a new type of therapy designed to reduce the production of specific proteins in the body. By targeting harmful proteins, it may help protect cells and slow the progression of certain diseases.

How it works: siRNA works by interrupting the process that makes proteins in cells. By targeting certain proteins, it can stop their production or reduce their levels.

Why it’s being tested for Parkinson’s: In diseases like Parkinson’s, certain proteins can build up in the brain and cause damage. siRNA therapy aims to reduce the levels of these harmful proteins, potentially slowing disease progression.

What is the siRNA therapy in this clinical trial designed to do?

This siRNA therapy targets α-synuclein, a protein linked to the progression of Parkinson’s.

Targeting α-synuclein: α-synuclein is a protein that can clump together in the brain and damage nerve cells, leading to Parkinson’s symptoms.

Reducing α-synuclein: This siRNA therapy is designed to work by lowering the levels of α-synuclein in the brain, which may help protect nerve cells and slow the progression of the disease.

How is siRNA therapy different from other treatments?

This siRNA therapy is a new approach designed to address the underlying cause of Parkinson’s, offering a different approach from current treatments.

Current treatments: Current treatments focus on managing symptoms. While they can help some people with their symptoms, these medicines often lose effectiveness as the disease progresses and may cause side effects. They don’t target the root cause of Parkinson’s. 

How siRNA therapy works: siRNA therapy focuses on lowering α-synuclein levels, a protein linked to disease progression. Scientists hope it will provide long-term benefits beyond symptom management.


About the clinical trial

Key questions and considerations


What are the key facts about this clinical trial?

This clinical trial is testing an siRNA therapy for people with Parkinson’s. The siRNA therapy will be given through an injection into the lower spine.

The trial is placebo-controlled, meaning some participants will receive the siRNA therapy, while others will receive a placebo. Participants will be randomly assigned to the treatment, with a 3 in 4 chance of receiving the siRNA therapy, and a 1 in 4 chance of receiving the placebo.

The trial will assess how the siRNA therapy affects the body, how the body processes it, and the best dose level.

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What are the potential risks and benefits?

This clinical trial is testing a new siRNA therapy for Parkinson’s. At this stage, this siRNA therapy has no known health benefits.

By participating in the clinical trial, the data collected from you may help researchers and doctors learn more about siRNA therapy and its potential to benefit patients with Parkinson’s or similar conditions in the future.

Learn More

What will happen during the PROSPECT clinical trial?

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Screening

Up to 6 weeks before the clinical trial starts

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Clinical trial treatment

First dose

Day 1

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Follow-up after first dose

From Week 1 until the second dose

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Clinical trial treatment

Second dose

Between Weeks 12 and 24

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Follow-up after second dose

Until 24 weeks after the second dose

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Optional follow-up

Up to 24 weeks after the 24-week follow-up

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Find your nearest clinical trial center

To find your nearest center for our siRNA therapy clinical trial for sporadic Parkinson’s, please visit ClinicalTrials.gov.
There, you can see detailed information about where the clinical trial is taking place.

Find a trial center

What are the key facts about this clinical trial?

This clinical trial is testing an siRNA therapy for people with Parkinson’s. The siRNA (small interfering RNA) therapy will be given through an injection into the lower spine.

The trial is placebo-controlled, meaning some participants will receive the siRNA therapy, while others will receive a placebo. Participants will be randomly assigned to the treatment, with a 3 in 4 chance of receiving the siRNA therapy, and a 1 in 4 chance of receiving the placebo.

The trial will assess how the siRNA therapy affects the body, how the body processes it, and the best dose level.

  • First-in-human therapy: This is the first time the siRNA therapy is being tested in people. The clinical trial has two parts:
    • In the first part, each dose will be tested in approximately 48 healthy volunteers, who do not have Parkinson’s.
    • Once initial assessments of the safety and effectiveness of the siRNA therapy have been completed, it will then be tested in approximately 60 participants with Parkinson’s. Details of this part of the clinical trial are explained below.
  • Trial locations: The clinical trial will take place at sites across the US, UK, Germany, the Netherlands, and Japan.
  • How treatment is decided: Participants will be chosen by chance (randomly assigned) to receive either the siRNA therapy or a placebo:
    • Participants have a 3 in 4 chance of receiving the siRNA therapy.
    • Participants have a 1 in 4 chance of receiving the placebo, which is administered like the siRNA therapy but does not contain any medicine.
  • How treatment is given: The siRNA therapy or placebo will be administered through an intrathecal injection. This involves placing a needle in the lower back to deliver the therapy directly into the cerebrospinal fluid (the fluid that surrounds the spinal cord and brain).
  • Number of doses participants will receive: Participants will receive a total of two injections of either the siRNA therapy or placebo. The second injection will be given sometime between 12 and 24 weeks after the first injection.
  • Dose levels:
    • The trial is testing up to five different dose levels of the siRNA therapy.
    • Participants will receive one of the dose levels of the siRNA therapy.
    • The trial will test different dose levels in stages.
    • This helps researchers determine the safest and most effective dose.
    • The dose a participant receives will depend on when they join the clinical trial.
  • Voluntary participation: Participation in the clinical trial is voluntary, and you may leave at any time.

What are the potential risks and benefits?

This clinical trial is testing a new siRNA therapy for Parkinson’s. At this stage, this siRNA therapy has no known health benefits.

By participating in the clinical trial, the data collected from you may help researchers and doctors learn more about siRNA therapy and its potential to benefit patients with Parkinson’s or similar conditions in the future.

Benefits

  • If effective, the siRNA therapy may help slow the progression of Parkinson’s.
  • Participating in this clinical trial will contribute valuable data that could advance understanding and help improve future treatment options for people with Parkinson’s.

Risks

  • This is the first time this siRNA therapy is being tested in humans. There is no prior information about its effects on people, and safety data so far are based on animal studies and similar therapies.
  • All clinical trials involve some level of risk, and individual risks may vary.
  • Researchers take every measure to ensure safety, but each clinical trial carries its own unique risks.

To learn more about the risks and benefits of participating, please email Jim Howley, Global Lead, Patient Advocacy and Engagement at Prevail.Patients@lilly.com or talk to your healthcare team.

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Screening

Up to 6 weeks before the clinical trial starts

What will happen

At your nearest clinical trial center we will:

Duration

  • Screening will take about 6 weeks. All screening visits will take place at the clinical trial site, and you won’t need to stay overnight.
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Clinical trial treatment: first dose

Day 1

What will happen

  • You will be admitted to the clinical trial center for 3–4 nights.
  • You’ll receive the first dose of the siRNA therapy or placebo through an injection into the space around your spinal cord (intrathecal injection).
  • This involves placing a needle in the lower back to deliver the therapy directly into the CSF (the fluid that surrounds the spinal cord and brain).
  • A small sample of spinal fluid will be collected before the injection.

After the procedure

  • You’ll stay at the clinical trial center under close monitoring for 2–3 days, depending on your recovery.
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Follow-up after first dose

From Week 1 until the second dose

What will happen

After the first dose, you’ll have follow-up visits starting at Week 1 and continuing at regular intervals until the second dose, which will be given between Weeks 12 and 24.

  • We’ll check your overall health with physical and neurological exams.
  • Blood and urine samples will be taken.
  • Vital signs and heart monitoring (ECG) will be done.
  • Samples of CSF from the spine will be collected by a lumbar puncture at some visits.
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Clinical trial treatment: second dose

Between Weeks 12 and 24

What will happen

  • The second dose will be scheduled between Weeks 12 and 24.
  • You will be admitted to the clinical trial center for 3–4 nights.
  • The procedure will be similar to the first dose, with another intrathecal injection and spinal fluid collection.

After the procedure

  • You’ll stay at the clinical trial center under close monitoring for 2–3 days, depending on your recovery.
Graphic of a calendar

Follow-up after second dose

Until 24 weeks after the second dose

What will happen

  • Regular visits approximately every 4–6 weeks until 24 weeks after the second dose.
  • We’ll continue monitoring you and collect additional blood, urine, and CSF samples.
Graphic of a stethoscope

Optional follow-up

Up to 24 weeks after the 24-week follow-up

  • You may be invited to continue with an additional 24 weeks of monitoring after the 24-week follow-up.
  • If you choose to participate, a separate informed consent form for this period will be provided for you to review.

Definitions

β-glucocerebrosidase (GCase)

An enzyme in the body. It helps break down fatty substances. These substances are recycled inside lysosomes, which are the recycling centers of cells. If GCase doesn’t work properly or is missing, fat builds up in lysosomes. This buildup happens in places like the spleen, liver, and bone marrow. It can cause health problems, such as Gaucher disease.

Cerebrospinal fluid (CSF)

A clear fluid that surrounds and cushions the brain and spinal cord, protecting them and helping transport nutrients and waste.

Cisterna magna

An area at the base of the skull where the brain and the spinal cord meet. This space is filled with cerebrospinal fluid and can be used by doctors to deliver treatments directly to the brain and spinal cord.

Clinical trials

Research studies that test new treatments or procedures in people to make sure they are safe and work well.

Dopamine transporter single-photon emission computed tomography (DaT-SPECT)

A scan that is used to diagnose neurodegenerative Parkinson’s disease from other types of Parkinson’s disease. For example, Parkinson’s disease caused by medicines or reduced blood supply to the brain.

Electrocardiogram (ECG)

A test that checks the heart’s rhythm and electrical activity using small sensors attached to the skin.

Enzyme replacement therapy (ERT)

A treatment that gives the body enzymes it’s missing or that aren’t working properly. For Gaucher disease, ERT provides a replacement for the GCase enzyme through an infusion. This helps reduce the buildup of fat in the body and manage symptoms.

Frontotemporal dementia (FTD)

A type of dementia that gets worse over time. It damages the brain’s frontal and temporal lobes. These areas control personality, behavior, language, and movement, which means FTD can lead to significant changes in how a person acts, communicates, and moves.

FTD with GRN genetic variants

FTD is a type of dementia that damages the brain’s frontal and temporal lobes, causing changes in personality, behavior, language, and movement.

About 5–10% of FTD cases are linked to genetic variants in the GRN gene. The GRN gene provides instructions for making progranulin, a protein needed to keep brain cells healthy. Genetic variants in GRN lead to lower levels of progranulin, causing brain cell damage and faster disease progression. People with these genetic variants often experience more severe and rapidly worsening symptoms.

GBA1 genetic variant

The GBA1 gene gives cells the instructions to make the GCase enzyme. This enzyme helps break down fatty substances inside lysosomes, which are the cell’s recycling centers. A GBA1 genetic variant is a change in this gene. This change can stop the GCase enzyme from working properly. When this happens, fatty substances build up in the body. This buildup can cause Gaucher disease or increase the risk of Parkinson’s disease.

Gaucher disease (GD)

A rare condition passed down through families, caused by changes (genetic variants) in the GBA1 gene. These changes affect a specific enzyme called GCase, which is needed to break down certain fatty substances. When GCase doesn’t work properly, these substances build up in lysosomes, the recycling centers of cells. Over time, this buildup can affect organs like the spleen, liver, and bone marrow, causing symptoms such as fatigue, bone pain, and organ swelling.

Gene therapy

A type of treatment that uses genetic material, such as DNA or RNA, to fix or replace faulty genes in the body. This treats or prevents certain diseases by enabling the genes to work as they should.

Genetic variant

A genetic variant is a change in a gene that can affect how it works. Changes in genes are mostly harmless. But, in some cases, they can make the body work differently and increase the risk of certain diseases. Genetic variants were previously called ‘mutations’.

Immunosuppressants

Medicines that lower the activity of the immune system. In gene therapy, they are used to reduce the chances of the immune system reacting to the inactivated virus that delivers the gene therapy to cells.

Informed Consent Form (ICF)

A document that provides important details about a clinical trial. It explains the potential risks and what is required before, during, and after the clinical trial. It also outlines the rights of participants. Participants sign the form to show they understand the clinical trial and agree to take part.

Infusion

A way of delivering fluids, including medicine, directly into the bloodstream using a needle or small tube.

Intravenous / intravenously (IV)

A method of giving medicine or fluids directly into a vein.

Lumbar puncture

A medical procedure where a small sample of cerebrospinal fluid is taken from the lower back using a needle. It’s sometimes called a spinal tap.

Lysosomes

Small parts of cells that act as recycling centers. They break down and recycle waste materials, including fatty substances, to keep the cells healthy. When lysosomes don’t work properly, these substances can build up and cause health problems, such as in Gaucher disease.

Magnetic resonance imaging (MRI)

A medical scan that uses powerful magnets and radio waves to create detailed images of the inside of the body, like the brain or spine.

Parkinson’s disease (PD)

A brain condition that affects movement. It happens when certain brain cells that produce a chemical called dopamine stop working properly. Without enough dopamine, the brain cannot send proper signals to the body. This can cause symptoms like tremors, stiffness, slow movements, and trouble with balance.

Parkinson’s disease with GBA1 genetic variants

Parkinson’s disease is a brain condition that affects movement, caused by the loss of brain cells that produce dopamine. Without enough dopamine, symptoms like tremors, stiffness, and slow movements can occur.

Some cases of Parkinson’s are linked to genetic variants in a gene called GBA1, the most common genetic risk factor for the condition. These genetic variants increase the risk of developing Parkinson’s and can lead to earlier and faster-progressing symptoms.

Peripheral vein

A vein found in areas like the arms, hands, legs, or feet. These veins are closer to the surface of the body and are commonly used for giving medications or drawing blood.

Placebo-controlled

In a clinical trial where there are two groups of participants, one group receives the active treatment or intervention, while the other group receives an inactive treatment or intervention (the placebo). The placebo is administered in the same way as the active treatment but does not contain any medicine.

Small interfering RNA (siRNA)

A type of therapy that uses small pieces of RNA, a natural molecule in cells, to block specific genes from making harmful proteins. siRNA works by ‘silencing’ genes that may cause or worsen certain diseases. This therapy is different from traditional gene therapy, as it focuses on turning off harmful gene activity rather than replacing or fixing genes.

Substrate reduction therapy (SRT)

An oral treatment (tablet) used for Gaucher disease. It works by partially stopping the body from making fatty substances. These substances are usually broken down by an enzyme called GCase. When GCase doesn’t work properly, these substances build up in lysosomes, the recycling centers of cells. SRT helps reduce this buildup and manage symptoms caused by Gaucher disease, such as organ swelling, fatigue, and bone pain.

Type 1 Gaucher disease

Type 1 Gaucher disease is the most common form of Gaucher disease, a rare inherited condition caused by genetic variants in the GBA1 gene. These genetic variants affect an enzyme called GCase, leading to a buildup of fatty substances in lysosomes, the recycling centers of cells.

Type 1 Gaucher disease usually begins during adolescence but can start at any age. Symptoms include bone pain, fractures, enlarged organs, bruising, and fatigue. Unlike other types, Type 1 does not typically affect the brain or spinal cord.

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