ALN-HTT02 for Huntington's Disease

Recruiting at 11 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

Trial Summary

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.

What data supports the effectiveness of the treatment ALN-HTT02 for Huntington's Disease?

Research shows that reducing the levels of the huntingtin protein, which ALN-HTT02 aims to do, has been beneficial in animal models of Huntington's Disease, improving motor and cognitive symptoms. Similar treatments that lower huntingtin protein levels have shown promise in early human trials, suggesting potential benefits for ALN-HTT02. ^{1 2 3 4 5}

Is ALN-HTT02 safe for humans?

In a study of a similar treatment, RG6042, which also reduces huntingtin protein levels, it was found to be generally safe and well tolerated in humans over a 4-month period. Additionally, reducing huntingtin protein in animal studies was generally safe and well tolerated. ^{1 5 6 7 8}

How is the drug ALN-HTT02 different from other treatments for Huntington's Disease?

ALN-HTT02 is unique because it targets the underlying cause of Huntington's Disease by reducing the levels of the mutant huntingtin protein, which is responsible for the disease's progression. This approach is different from other treatments that mainly address symptoms rather than the root cause. ^{1 4 5 9 10}

What is the purpose of this trial?

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

Research Team

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Eligibility Criteria

Inclusion Criteria

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

Timeline

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

Treatment Details

Interventions

• ALN-HTT02

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

The importance of integrating basic and clinical research toward the development of new therapies for Huntington disease. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Emerging therapies in Huntington's disease. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: analysis of 24 month observational data. [2022]

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

Clinical Outcomes and Selection Criteria for Prodromal Huntington's Disease Trials. [2021]

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

Huntingtin-Lowering Therapies for Huntington Disease: A Review of the Evidence of Potential Benefits and Risks. [2021]

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

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

7. 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]

8. France pubmed.ncbi.nlm.nih.gov

In vivo proof-of-concept of removal of the huntingtin caspase cleavage motif-encoding exon 12 approach in the YAC128 mouse model of Huntington's disease. [2017]

9. England 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. [2016]

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

Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington's disease. [2022]