What is the mechanism of action of this treatment?

The most common treatments for Huntington's Disease (HD) include VMAT2 inhibitors like tetrabenazine, deutetrabenazine, and valbenazine, which reduce chorea by depleting monoamines such as dopamine. This is significant for HD patients as it helps manage motor symptoms that impair daily functioning. Additionally, antisense oligonucleotides (ASOs) like tominersen target the mutant huntingtin (mHTT) protein by binding to its mRNA, thereby reducing its production. This mechanism is particularly important as it aims to lower the levels of the toxic protein directly involved in HD progression, offering a potential disease-modifying approach.

What side effects are associated with this type of intervention?

Common treatments for Huntington's Disease include VMAT2 inhibitors like tetrabenazine and deutetrabenazine, which are used to manage chorea. Tetrabenazine can cause sedation, akathisia, parkinsonism, and depressed mood, but these symptoms often resolve with dose adjustments. Deutetrabenazine has a longer duration of action and an improved side effect profile compared to tetrabenazine. Antisense oligonucleotides, such as Tominersen, are being studied for their potential to target mutant huntingtin protein. While specific side effects of Tominersen are still under investigation, antisense oligonucleotides in general can cause injection site reactions, flu-like symptoms, and elevated liver enzymes. Patients should discuss these potential side effects with their healthcare provider to make an informed decision.

What prior FDA approvals exist?

As of now, there are no FDA-approved antisense oligonucleotide therapies specifically targeting the mutant huntingtin protein for Huntington's Disease. The current FDA-approved treatments for Huntington's Disease primarily focus on managing symptoms rather than modifying the disease course. These include tetrabenazine and deutetrabenazine for chorea (involuntary movements) associated with Huntington's Disease. Other medications may be used off-label to manage psychiatric symptoms and other complications, but they do not target the underlying genetic cause of the disease.

What other types of research exist?

Promising novel alternatives to Tominersen for Huntington's Disease patients include: 1) Gene therapy approaches, such as those involving adeno-associated virus (AAV) vectors to deliver therapeutic genes directly to the brain. 2) RNA interference (RNAi) therapies like Patisiran, which target and degrade mutant huntingtin mRNA. 3) CRISPR/Cas9-based gene editing techniques aimed at correcting the genetic mutation responsible for HD. 4) Small molecule inhibitors that modulate the activity of the huntingtin protein or its interactions. These alternatives are in various stages of research and clinical trials, showing potential for future treatment options.

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Tominersen for Huntington's Disease

Phase 2

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Total body weight > 40 kg and a body mass index within the range of 18-32 kg/m2

Huntington's disease (HD) gene expansion mutation carrier status with a CAP score of 400-500 inclusive

Must not have

Anti-platelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the study, including, but not limited to, aspirin (unless </= 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and heparin

Current or previous use of an ASO (including small interfering RNA) or any HTT lowering therapy (including tominersen)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to 16 months

Summary

This trial is testing a drug called tominersen to see if it is safe and effective for people in the early stages of Huntington's Disease. The drug aims to reduce a harmful protein that causes the disease, potentially slowing its progression. Tominersen targets and reduces the mutant huntingtin protein, which is implicated in Huntington's Disease.

Who is the study for?

This trial is for adults over 40 kg with a BMI of 18-32 who have Huntington's disease and a specific genetic mutation score. It's open to those in the early stages or just before symptoms start, but not to anyone who has used gene therapy, brain surgery, certain medications recently, or women who are pregnant or planning pregnancy.

What is being tested?

The study tests Tominersen (at two different doses: 60 mg and 100 mg) against a placebo to check its safety and effectiveness in slowing down Huntington's Disease progression. Participants will be randomly assigned to receive either the drug or placebo.

What are the potential side effects?

While the side effects aren't specified here, similar drugs can cause reactions at injection sites, flu-like symptoms, potential liver issues, nervous system problems like dizziness or seizures, and could affect blood clotting.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I weigh more than 40 kg and my BMI is between 18-32.

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I carry the Huntington's disease gene with a CAP score between 400-500.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken any blood thinners, except possibly low-dose aspirin, in the last 14 days.

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I have used gene-silencing drugs for my condition.

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I have had gene therapy, cell transplantation, or brain surgery.

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I have hydrocephalus.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to 16 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to 16 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to 16 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from baseline in Total Functional Capacity (TFC) Scores (U.S. sites) at 16 months

Change from baseline in composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. sites) at 16 months

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Tominersen 60 mgExperimental Treatment1 Intervention

Group II: Tominersen 100 mgExperimental Treatment1 Intervention

Group III: PlaceboPlacebo Group1 Intervention

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Huntington's Disease (HD) include VMAT2 inhibitors like tetrabenazine, deutetrabenazine, and valbenazine, which reduce chorea by depleting monoamines such as dopamine. This is significant for HD patients as it helps manage motor symptoms that impair daily functioning. Additionally, antisense oligonucleotides (ASOs) like tominersen target the mutant huntingtin (mHTT) protein by binding to its mRNA, thereby reducing its production. This mechanism is particularly important as it aims to lower the levels of the toxic protein directly involved in HD progression, offering a potential disease-modifying approach.