SAGE-718 for Huntington's Disease

No longer recruiting at 22 trial locations

Overseen By Tatiana Oreshina

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sage Therapeutics

Must not be taking: Gene therapy, Antisense oligonucleotides

Disqualifiers: Alzheimer's, Parkinson's, Gastric surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of SAGE-718, a new medication for people with Huntington's Disease (HD). Participants will receive SAGE-718 in softgel form to assess their tolerance over time. The trial seeks individuals with a genetic confirmation of HD who can travel to study centers and abstain from alcohol and drugs during the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for HD.

Will I have to stop taking my current medications?

The trial requires that you do not take any prohibited medications within 30 days before starting and during the study. However, it does not specify which medications are prohibited, so you should discuss your current medications with the study team.

Is there any evidence suggesting that SAGE-718 is likely to be safe for humans?

Research has shown that SAGE-718 was generally well-tolerated in past studies. Earlier research found no new safety issues, and any side effects were mild to moderate. Mild side effects were not serious and did not cause major problems for participants. This suggests the treatment might be safe for humans, but further studies are needed to confirm this. ^{1 2 3 4 5}

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

Researchers are excited about SAGE-718 for Huntington's Disease because it offers a unique approach compared to existing treatments like tetrabenazine and deutetrabenazine, which primarily focus on managing movement problems. SAGE-718 works differently by targeting cognitive symptoms, which are a significant and challenging aspect of Huntington's Disease. This treatment aims to improve thinking and memory, potentially enhancing quality of life for patients in a way current options do not fully address. By focusing on these cognitive aspects, SAGE-718 could fill an important gap in the treatment landscape for Huntington's Disease.

What evidence suggests that SAGE-718 might be an effective treatment for Huntington's Disease?

Research is investigating SAGE-718 for its potential to address thinking and memory problems in people with Huntington's Disease. Participants in this trial will receive SAGE-718 to test its effectiveness. Although earlier studies did not achieve their main goals, one analysis showed that some patients improved their cognitive scores by 2.3 points. SAGE-718 enhances a specific brain receptor, which might support better brain function. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I am between 25 and 65 years old.

I can travel to the study center and continue to do so for the study duration.

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

Exclusion Criteria

Participants with confirmation of enrolment in the placebo arm of these investigational trials would not be excluded

I have had surgery that affects my stomach or intestines.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SAGE-718 from Day 1 up to Month 48

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• SAGE-718

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort 3 (De Novo) Experimental Treatment 1 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 Treatment 1 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 Treatment 1 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.

Who Is Running the Clinical Trial?

Sage Therapeutics

Lead Sponsor

Trials

51

Recruited

11,000+

Founded

2010

Headquarters

Cambridge, USA

Known For

Brain Health Medicines

Top Products

ZURZUVAE (zuranolone), SAGE-324

Published Research Related to This Trial

Tiapride has been shown to effectively improve chorea symptoms in Huntington's Disease patients, with many experts preferring it as the first-line treatment, especially for those with behavioral symptoms.

The withdrawal of tiapride from the Dutch market has caused significant disruption for patients, with 50% needing to import the medication, highlighting its importance and lack of suitable alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Many Faces of Huntington's Chorea Treatment: The Impact of Sudden Withdrawal of Tiapride after 40 Years of Use and a Systematic Review. Feleus, S., van Schaijk, M., Roos, RAC., et al.[2022]

Citations

1. investor.sagerx.com investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-announces-topline-results-phase-2-dimension

The Phase 2 DIMENSION Study did ... ... (SAGE-718) in the Treatment of Cognitive Impairment Associated with Huntington's Disease. The Phase 2 DIMENSION Study did not meet its primary endpoint.

2. neurologylive.com neurologylive.com/view/huntington-agent-sage-718-discontinued-following-disappointing-phase-2-dimension-trial-results

Huntington Agent SAGE-718 to be Discontinued Following ... The analysis, which included 26 patients (mean age, 67 years; 69.2% women), demonstrated a statistically significant 2.3-point improvement in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05107128

A Study to Evaluate the Effect of SAGE-718 on Cognitive ... The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance and functioning in participants with HD. Official Title.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38988035/

Dalzanemdor (SAGE-718), a novel, investigational N ... Dalzanemdor (SAGE-718) is a novel, investigational NMDAR PAM being evaluated for the potential treatment of cognitive impairment in these disorders.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05358821

NCT05358821 | 28-Day Study of SAGE-718 on ... The primary purpose of this study is to assess the magnitude of the baseline difference between participants with early Huntington's Disease (HD) and healthy ...

6. isrctn.com isrctn.com/ISRCTN47421449

A study to assess the long-term safety of SAGE-718 in ... A phase III, multicenter, open-label safety study to evaluate the long-term safety and tolerability of SAGE-718 in participants with Huntington's disease.