What side effects are associated with this type of intervention?

Common treatments for Huntington's Disease include medications like tetrabenazine and antipsychotics, which can cause side effects such as drowsiness, restlessness, and depression. For NMDA receptor modulation, memantine is a relevant example. Known side effects of memantine include dizziness, headache, confusion, and in some cases, hallucinations and worsened neuropsychiatric symptoms. These side effects highlight the need for careful monitoring when using NMDA receptor modulators in HD treatment.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically targeting NMDA receptor modulation for Huntington's Disease. The primary FDA-approved drugs for Huntington's Disease include tetrabenazine and deutetrabenazine, which are used to manage chorea associated with the condition. These drugs work by depleting monoamines such as dopamine, serotonin, and norepinephrine. Other treatments focus on symptomatic relief and supportive care rather than targeting the underlying disease mechanisms.

What other types of research exist?

Promising alternatives to SAGE-718 for Huntington's Disease patients include rivastigmine, which has shown slight improvement in motor and cognitive impairment in HD patients. Additionally, memantine, an NMDA receptor antagonist, has been studied for various neurodegenerative diseases and may offer potential benefits for HD patients.

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SAGE-718 for Huntington's Disease

Phase 3

Recruiting

Research Sponsored by Sage Therapeutics

Eligibility Criteria Checklist

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

Must have

Be at least 25 years old, but not older than 65 years of age at Screening

Genetically confirmed disease with cytosine-adenine-guanine (CAG) expansion ≥40

Must not have

Have previous exposure to gene therapy, or have participated in any other HD investigational drug, biologic, or device trial within 180 days or a non-HD drug, biologic or device trial within 30 days or 5 half-lives (whichever is longer). Additionally, participants who have received treatment with antisense oligonucleotides or a messenger ribonucleic acid (mRNA) splicing modifier will be excluded

Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any related procedures that interfere with gastrointestinal transit

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 49 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new softgel capsule called SAGE-718 to see if it is safe for people with Huntington's Disease.

Who is the study for?

This trial is for adults aged 25-65 with genetically confirmed Huntington's Disease, a CAG expansion ≥40, and specific cognitive or functional scores. Participants must avoid drugs of abuse, alcohol before visits, and be able to travel to the study center. They should not have juvenile HD features or other neurodegenerative conditions.

What is being tested?

The trial is testing SAGE-718 softgel capsules' safety and tolerability in those with Huntington's Disease. It aims to see how well participants handle the treatment over time.

What are the potential side effects?

Specific side effects are not listed but will focus on any adverse reactions related to SAGE-718 capsules which include its components like soy lecithin.

Eligibility Criteria

Inclusion Criteria

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

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I am between 25 and 65 years old.

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My genetic test shows a CAG expansion of 40 or more.

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I do not have juvenile Huntington's disease.

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My CAP score is 90 or higher.

Exclusion Criteria

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

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I have not been in any drug or device trials recently, nor have I had gene therapy.

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I have had surgery that affects my stomach or intestines.

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I am allergic to soy lecithin or other components in SAGE-718.

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I have a neurodegenerative condition like Alzheimer's, but not Huntington's Disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 49 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 49 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 49 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 Columbia Suicide Severity Rating Scale (C-SSRS) Responses

Number of Participants Who Withdrew Due to Adverse Events (AEs)

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Severity of TEAEs

+1 more

Side effects data

From 2022 Phase 2 trial • 18 Patients • NCT04476017

Large intestine polyp

Asthenia

Urinary tract infection

Skin laceration

Activated partial thromboplastin time prolonged

International normalized ratio increased

Leukocyturia

Eye contusions

Fall

100%

80%

60%

40%

20%

Study treatment Arm

Part A: SAGE-718 3 mg

Part B: SAGE-718 3 mg

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Cohort 3 (De Novo)Experimental Treatment1 Intervention

Participants who were not previously included in any SAGE-718 clinical study. Participants will receive Sage-718 from Day 1 up to Month 48.

Group II: Cohort 2 (Gap Rollover)Experimental Treatment1 Intervention

Participants from studies 718-CIH-201 (NCT05107128) and 718-CIH-202 (NCT05358821) who will sign the informed consent for study 718-CIH-301 after a gap of \>7 days after the last day of the corresponding parent study. Participants will receive Sage-718 from Day 1 up to Month 48.

Group III: Cohort 1 (Direct Rollover)Experimental Treatment1 Intervention

Participants from studies 718-CIH-201 (NCT05107128) and 718-CIH-202 (NCT05358821) who will sign the informed consent for study 718-CIH-301 ≤7 days after the last day of the corresponding parent study. Participants will receive Sage-718 from Day 1 up to Month 48.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

SAGE-718

2020

Completed Phase 2

~650

0 / 8Eligibility 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) often target the modulation of neurotransmitter systems to manage symptoms. SAGE-718, for instance, focuses on NMDA receptor modulation, which is crucial because NMDA receptors play a significant role in synaptic plasticity and cognitive function. By modulating these receptors, SAGE-718 aims to improve cognitive deficits associated with HD. Other treatments may include dopamine-depleting agents like tetrabenazine to manage chorea (involuntary movements) and antipsychotics to address psychiatric symptoms. Understanding these mechanisms is vital for HD patients as it helps tailor treatments to manage specific symptoms effectively, potentially improving their quality of life.

Genetic rodent models of brain disorders: Perspectives on experimental approaches and therapeutic strategies.New symptomatic therapies for Huntington disease.Ketamine Suppresses the Ventral Striatal Response to Reward Anticipation: A Cross-Species Translational Neuroimaging Study.