Tominersen for Huntington's Disease

Not currently recruiting at 118 trial locations

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

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Gene therapy, Hydrocephalus, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests tominersen, a potential treatment for Huntington's Disease (HD), to determine its safety and effectiveness. Researchers aim to compare tominersen to a placebo in individuals showing early signs of HD. Participants must have a diagnosis of either prodromal (early symptoms) or early manifest HD and should not have used similar treatments before. This trial might suit those living with HD who meet these criteria. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to early-stage findings.

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking anti-platelet or anticoagulant medications (blood thinners) like aspirin (unless 81 mg/day or less), clopidogrel, and warfarin at least 14 days before starting the study. Other medications are not specifically mentioned, so it's best to discuss with the study team.

Is there any evidence suggesting that tominersen is likely to be safe for humans?

Research shows that tominersen has been tested in people with early Huntington's disease. Previous patients generally tolerated the drug well. One study found that the main goals of safety and tolerability were achieved, even though specific details weren't provided, indicating that people didn't have major problems with the drug.

Another study associated tominersen with a decrease in a harmful protein, a positive sign for its potential benefits. While these findings are encouraging, research is still ongoing. Always consult your doctor to understand what this means for your situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Huntington's Disease?

Tominersen is unique because it targets the root cause of Huntington's disease by reducing the production of the huntingtin protein, which is responsible for the disease's progression. Unlike current treatments that primarily manage symptoms, Tominersen works at the genetic level, potentially slowing or halting the disease itself. Researchers are excited about this treatment because it offers a more direct approach to tackling the underlying biology of Huntington's, which could lead to more effective and long-lasting results.

What evidence suggests that tominersen might be an effective treatment for Huntington's Disease?

Research shows that tominersen, which participants in this trial may receive, might help treat Huntington's Disease by lowering levels of the harmful protein mutant huntingtin (mHTT). Studies have found that reducing mHTT in the fluid around the brain and spine can improve patients' health. In earlier research, participants experienced dose-dependent reductions in mHTT, suggesting that the treatment could alter the disease's course, not just ease symptoms. Additionally, evidence indicates that as mHTT levels drop, patients' conditions improve. These findings suggest that tominersen could be promising in managing Huntington's Disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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.

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

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

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 hydrocephalus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tominersen or placebo for 16 months to evaluate safety, biomarkers, and efficacy

16 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tominersen

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.

How Is the Trial Designed?

Group I: Tominersen 60 milligrams (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

Published Research Related to This Trial

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]

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 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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03761849

NCT03761849 | A Study to Evaluate the Efficacy and ... In this outcome measure, participants with 1.2 or higher point score decrease from the Baseline Composite Unified Huntington's Disease Rating Scale- cUHDRS ...

2. neurology.org neurology.org/doi/10.1212/WNL.90.15_supplement.CT.002

Effects of IONIS-HTTRx in Patients with Early Huntington's ... Significant, dose-dependent reductions in CSF mutant HTT (mHTT) were observed. Conclusions: ASO technology has the potential to provide disease-modifying ...

3. ir.ionis.com ir.ionis.com/news-releases/news-release-details/new-data-ionis-htt-rx-phase-12-study-demonstrates-correlation

New Data from IONIS-HTT Rx Phase 1/2 Study ... The study demonstrated correlations between reductions in mutant huntingtin (mHTT), the disease-causing protein, and improvements in clinical measures of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11091610/

Huntington's Disease Clinical Trials Corner: March 2024 The Clinical Trials Update is a regular feature devoted to highlighting ongoing and recently completed clinical trials in Huntington's disease (HD).

5. en.hdbuzz.net en.hdbuzz.net/427/

Roche provides an update on tominersen Tominersen is an experimental drug developed by Roche that is designed to treat Huntington's disease ... data from the GENERATION HD2 trial ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29620999/

Dose-Dependent Lowering of Mutant Huntingtin Using ... The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the ...