Tominersen for Huntington's Disease

Recruiting at 107 trial locations

Overseen By Reference Study ID Number: BN42489. https://forpatients.roche.com/

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Hoffmann-La Roche

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications?

The trial requires you to stop taking anti-platelet or anticoagulant medications 14 days before screening and during the study, unless it's aspirin at 81 mg/day or less. Other medications are not specified, so check with the study team.

What data supports the idea that the drug Tominersen for Huntington's Disease is an effective treatment?

The available research shows that Tominersen can lower the levels of a harmful protein in the fluid around the brain and spine in people with Huntington's Disease. This suggests it might help manage the disease. However, the research does not provide direct evidence of improvements in symptoms or compare it to other treatments. More studies are needed to confirm its effectiveness in treating Huntington's Disease. ^{1 2 3 4 5}

What safety data is available for tominersen in treating Huntington's Disease?

Safety data for tominersen, also known as IONIS-HTTRx, RG6042, RO7234292, ISIS-443139, and HTT ASO, has been gathered from multiple clinical studies. A population pharmacokinetic model was developed using data from 750 participants across five clinical studies, which included 6302 cerebrospinal fluid (CSF) and 5454 plasma samples. The studies identified significant covariates affecting tominersen pharmacokinetics, such as baseline total CSF protein, age, antidrug antibodies, body weight, and sex. This model helps guide dose selection for future trials, indicating a focus on understanding the drug's behavior in the body, which is crucial for assessing safety. Additionally, the GENERATION HD2 trial and other ongoing studies continue to evaluate tominersen's safety and efficacy. ^{1 2 3 6 7}

Is the drug tominersen a promising treatment for Huntington's Disease?

Yes, tominersen is a promising treatment for Huntington's Disease because it can lower the levels of the harmful protein that causes the disease. This drug works by targeting and reducing the mutant huntingtin protein in the brain, which is linked to the symptoms of Huntington's Disease. ^{1 2 3 6 8}

Eligibility Criteria

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.

Inclusion Criteria

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

You have early signs of Huntington's disease or are in the early stages of the disease.

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

Exclusion Criteria

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

I have used gene-silencing drugs for my condition.

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

Treatment Details

Interventions

• Placebo (Drug)
• Tominersen (Antisense Oligonucleotide)

Trial Overview 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.

Participant Groups

Group I: Tominersen 60 mg Experimental Treatment 1 Intervention

Group II: Tominersen 100 mg Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

Tominersen, an antisense oligonucleotide administered directly into the spinal fluid, effectively reduces mutant huntingtin protein levels in individuals with Huntington's disease, demonstrating a dose-dependent response.

A comprehensive pharmacokinetic model based on data from 750 participants across five studies was developed, identifying key factors like age and body weight that influence the drug's clearance, which will help optimize dosing in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a population pharmacokinetic model to characterize the pharmacokinetics of intrathecally administered tominersen in cerebrospinal fluid and plasma. Yamamoto, Y., Sanwald Ducray, P., Björnsson, M., et al.[2023]

A 36-year-old woman with the akinetic-rigid variant of Huntington's disease showed significant improvement in parkinsonism, bradykinesia, and dystonia after 5 days of intravenous amantadine treatment, as measured by the Unified Huntington's Disease Rating Scale.

This case suggests that amantadine, which increases dopamine levels in the brain, may be beneficial for patients with this specific variant of Huntington's disease, marking a novel application of the drug beyond its typical use in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amantadine in the akinetic-rigid variant of Huntington's disease. Magnet, MK., Bonelli, RM., Kapfhammer, HP.[2013]

The GENERATION HD2 trial is investigating the efficacy of tominersen, a potential treatment for Huntington's disease, highlighting ongoing efforts to find effective therapies for this condition.

The PROOF-HD trial has provided new insights into Huntington's disease, contributing to the understanding of treatment options and the landscape of current clinical trials in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Huntington's Disease Clinical Trials Corner: August 2023. Estevez-Fraga, C., Tabrizi, SJ., Wild, EJ.[2023]

CERE-120 (AAV2-NTN) therapy showed significant protective effects in a mouse model of Huntington's disease, improving motor function and reducing symptoms like clasping behavior.

The treatment also provided neuroprotection by preserving neurons in both the striatum and prefrontal cortex, suggesting that gene delivery of neurturin could be a promising approach for treating Huntington's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease. Ramaswamy, S., McBride, JL., Han, I., et al.[2019]

Transgenic and knock-in animal models of Huntington's disease (HD) are crucial for preclinical evaluation of treatment targets, leading to several promising approaches that have progressed to clinical trials.

Ongoing biomarker studies like TRACK-HD and PREDICT-HD are exploring new outcome measures, such as volumetric imaging and quantitative motor assessments, which may enhance the reliability and sensitivity of clinical trials for HD, potentially speeding up the development of effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches. Sampaio, C., Borowsky, B., Reilmann, R.[2022]

The phase 1-2a trial involving 46 adults with early Huntington's disease showed that the antisense oligonucleotide HTTRx was safe, with no serious adverse events reported and only mild adverse effects in 98% of patients.

HTTRx treatment led to significant dose-dependent reductions in mutant huntingtin levels in cerebrospinal fluid, achieving up to a 42% reduction at the highest dose, indicating its potential efficacy in targeting the underlying cause of Huntington's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Huntingtin Expression in Patients with Huntington's Disease. Tabrizi, SJ., Leavitt, BR., Landwehrmeyer, GB., et al.[2023]

The second edition of the Huntington’s Disease Clinical Trials Corner provides an overview of all currently registered and ongoing clinical trials, highlighting the importance of tracking advancements in treatment options for Huntington's Disease.

Key results from the IONIS-HTTRX trial and details on Wave Life Sciences' PRECISION-HD trials are summarized, indicating ongoing efforts to develop effective therapies for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Huntington’s Disease Clinical Trials Corner: February 2018 Rodrigues, FB., Wild, EJ.[2022]

In a study involving 227 participants with Huntington's disease, pridopidine at a dosage of 90 mg/day showed a potential improvement in motor function, although the primary analysis did not reach statistical significance (P = .08).

Pridopidine was generally well tolerated by participants, indicating it may be a safe option for further investigation in treating motor symptoms of Huntington's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington's disease. [2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Development of a population pharmacokinetic model to characterize the pharmacokinetics of intrathecally administered tominersen in cerebrospinal fluid and plasma. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Amantadine in the akinetic-rigid variant of Huntington's disease. [2013]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Huntington's Disease Clinical Trials Corner: August 2023. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Targeting Huntingtin Expression in Patients with Huntington's Disease. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Huntington’s Disease Clinical Trials Corner: February 2018 [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington's disease. [2022]