ALN-HTT02 for Huntington's Disease

Recruiting at 18 trial locations

Overseen By Alnylam Clinical Trial Information Line

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Alnylam Pharmaceuticals

Disqualifiers: Neurologic disease, Immune compromise, Liver enzymes, eGFR, others

Compensation: Varies

Number of Visits: Unknown

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALN-HTT02 for individuals with stage 2 or early stage 3 Huntington's disease, a condition affecting the brain and movement. The main goal is to determine the safety of ALN-HTT02 and how the body processes it. Participants will receive either a placebo (a harmless pill with no active drug) or ALN-HTT02. This trial suits those diagnosed with Huntington's disease at these specific stages. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ALN-HTT02 is likely to be safe for humans?

Research shows that ALN-HTT02 is being tested for safety and tolerability in people with Huntington's disease. Scientists aim to determine if individuals can handle the treatment and identify any side effects. In this early research stage, the primary goal is to detect negative reactions after a single dose. Although limited information is available, early studies prioritize safety. Participants are closely monitored for any issues. Those considering joining this trial can expect the team to carefully observe how their body responds to the treatment. ^{1 2 3 4 5}

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

Researchers are excited about ALN-HTT02 for Huntington's Disease because it works differently from current treatments, which mainly focus on managing symptoms. ALN-HTT02 is designed to target and reduce the production of the huntingtin protein, which is directly involved in the disease's progression. This approach offers a potential new way to tackle the root cause of Huntington's, rather than just alleviating its symptoms. Additionally, ALN-HTT02 is administered as a single dose, which could simplify treatment compared to existing therapies that often require ongoing administration.

What evidence suggests that ALN-HTT02 might be an effective treatment for Huntington's Disease?

Research has shown that ALN-HTT02 targets and reduces a protein called variant huntingtin, linked to Huntington's disease. Lowering this protein has shown promise in improving symptoms in both human studies and mouse experiments. Some studies reported a significant slowing of the disease, with up to a 75% reduction in its progression in certain cases. In this trial, participants will receive a single dose of ALN-HTT02, while others will receive a placebo during the double-blind part of the study. Although ALN-HTT02 is still under investigation and not yet approved, these findings suggest it could potentially help manage Huntington's disease. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with stage 2 or early stage 3 Huntington's Disease, as classified by the HD-ISS. It aims to include those who are experiencing specific stages of this neurological condition.

Inclusion Criteria

My condition is in stage 2 or early stage 3 of Huntington's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive a single dose of either ALN-HTT02 or placebo

Single dose administration

Open-label Treatment

Participants have the option to receive a single dose of ALN-HTT02

Single dose administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• ALN-HTT02

Trial Overview The study is testing ALN-HTT02, a potential new treatment for Huntington's Disease. Participants will receive either this drug or a placebo in order to compare effects on safety and how the body processes it.

How Is the Trial Designed?

Group I: ALN-HTT02 Experimental Treatment 1 Intervention

Participants will be administered a single dose of ALN-HTT02 during the Double-blind Part of the study. Participants who received ALN-HTT02 in the Double-blind part of the study will not receive an additional dose during the Open-label part of the study

Group II: Placebo + ALN-HTT02 Placebo Group 2 Interventions

Participants will be administered a single dose of placebo during the Double-blind Part of the study. Participants will have the option to receive a single dose of ALN-HTT02 during the Open-Label Part of the study.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Published Research Related to This Trial

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]

A recent phase 1/2a study involving 46 adults with early Huntington disease showed that the antisense oligonucleotide RG6042, which partially reduces huntingtin protein levels, was generally safe and well tolerated over four monthly doses.

Evidence from both human case studies and mouse models suggests that reducing variant huntingtin protein can improve symptoms and may not pose significant risks, indicating a positive risk-benefit profile for therapies targeting huntingtin levels in Huntington disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Huntingtin-Lowering Therapies for Huntington Disease: A Review of the Evidence of Potential Benefits and Risks. Leavitt, BR., Kordasiewicz, HB., Schobel, SA.[2021]

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]

High-capacity adenoviral (HC-Ad) vectors successfully delivered both truncated and full-length mutant huntingtin (htt) proteins in vitro and in vivo, leading to the formation of htt inclusions, which are markers of Huntington's disease pathology.

The study found that truncated mutant htt formed inclusions primarily in the cell nuclei, while full-length mutant htt inclusions localized to the cytoplasm, highlighting differences in their behavior and potential implications for understanding Huntington's disease mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inducing huntingtin inclusion formation in primary neuronal cell culture and in vivo by high-capacity adenoviral vectors expressing truncated and full-length huntingtin with polyglutamine expansion. Huang, B., Schiefer, J., Sass, C., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12231940/

Huntington's disease clinical trials update: March 2025 - PMC In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing phase I clinical trial of ALN-HTT02 from Alynlam Pharmaceuticals.

2. capella.alnylam.com capella.alnylam.com/wp-content/uploads/2024/11/Innovators-Forum_110724_Kevin-Sloan-HSG2024_uploaded.pdf

ALN-HTT02, a Novel C16-siRNA Conjugate for HTT-lowering ... ALN-HTT02 is an investigational drug being studied for the treatment of Huntington's disease. ALN-HTT02 is not approved by any health authority, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06585449

NCT06585449 | A Study to Evaluate ALN-HTT02 in Adult ... The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of a single dose of ALN-HTT02.

4. trial.medpath.com trial.medpath.com/news/092128eacfdb8d91/gene-therapy-achieves-first-successful-treatment-of-huntington-s-disease-slowing-progression-by-75

gene therapy - Huntington's disease - MedPath Three years after treatment, those receiving the high dose demonstrated an average 75% slowing of disease progression based on comprehensive ...

5. withpower.com withpower.com/trial/aln-htt02-for-huntingtons-disease-95385

ALN-HTT02 for Huntington's Disease Evidence from both human case studies and mouse models suggests that reducing variant huntingtin protein can improve symptoms and may not pose significant risks ...

6. clinicaltrials.alnylam.com clinicaltrials.alnylam.com/trials/6585449

ALN-HTT02-001 - Alnylam Clinical Trials The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of a single dose of ALN-HTT02.