SAGE-324 for Essential Tremor

No longer recruiting at 5 trial locations

Overseen By Carrie Vaudreuil, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sage Therapeutics

Must be taking: Propranolol

Must not be taking: Tremorgenic drugs

Disqualifiers: Substance abuse, Brain procedures, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test how different doses of SAGE-324, a new potential drug, can reduce tremors in people with essential tremor (ET), a condition that causes uncontrollable shaking, usually in the hands. Participants will receive varying doses of SAGE-324, either alone or with propranolol, a common treatment for tremors, to determine the most effective dose. The study seeks individuals who have experienced arm tremors for at least three years and are willing to pause other tremor medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants the chance to contribute to important advancements in ET treatment.

Will I have to stop taking my current medications?

You will need to stop taking medications for essential tremor, except for propranolol, at least 14 days or 5 half-lives before starting the trial. You can resume these medications after Day 97 of the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SAGE-324 has been tested in people with essential tremor and has a safety profile consistent with previous studies. This indicates that the side effects were anticipated and aligned with earlier findings. However, the treatment has not yet been proven safe or effective. Although specific side effects were not listed, no major new safety issues have emerged so far. As this treatment remains under investigation, participating in a trial may involve experiencing some side effects. The goal is to monitor and manage these while exploring its potential benefits for treating tremors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for essential tremor?

Most treatments for essential tremor typically involve beta-blockers like propranolol or anti-seizure medications. However, SAGE-324 stands out because it works by modulating the GABA system in the brain, which is different from how current treatments operate. Researchers are excited about SAGE-324 because it offers a novel approach that could provide relief for patients who haven't responded well to traditional medications. Additionally, SAGE-324 is being tested both as a monotherapy and as an adjunct therapy, offering versatile treatment options that could be tailored to individual patient needs.

What evidence suggests that SAGE-324 could be an effective treatment for essential tremor?

Research has shown that SAGE-324 has not been very effective in treating essential tremors. In a recent study, increasing the dose of SAGE-324 did not consistently improve tremor reduction. Additionally, SAGE-324 did not significantly reduce tremors compared to a placebo, a substance with no active medication. These findings suggest that SAGE-324 might not be an effective treatment for essential tremors at this time. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with Essential Tremor (ET) that's lasted at least 3 years. Participants must be willing to stop their ET medications before starting the study, except propranolol if it's been taken steadily. They can't have other neurological issues or use certain treatments like the Cala Trio bracelet, and they shouldn't have a history of substance abuse or dependence.

Inclusion Criteria

My arm strength score is 6 or more.

I am willing to stop my essential thrombocythemia (ET) treatment before starting the trial medication.

I do not have other major nerve system symptoms like uncontrolled movements or balance issues.

Exclusion Criteria

I have been using the Cala Trio bracelet for my ET for at least two weeks.

I am currently taking propranolol for a condition that is not essential tremor.

I haven't taken any new tremor-causing drugs or experienced alcohol withdrawal in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SAGE-324 or placebo, with dose adjustments over 90 days

13 weeks

Regular visits for dose adjustments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SAGE-324

Trial Overview The trial tests SAGE-324 against a placebo to see how different doses affect arm tremors in people with ET. It looks at whether one dose works better than another when no other tremor medications are used.

How Is the Trial Designed?

Group I: SAGE-324 60 mg Experimental Treatment 1 Intervention

Participants will receive SAGE-324: 15 mg, 30 mg, 45 mg, and 60 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Group II: SAGE-324 30 mg Experimental Treatment 1 Intervention

Participants will receive SAGE-324, 30 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Group III: SAGE-324 15 mg Experimental Treatment 1 Intervention

Participants will receive SAGE-324, 15 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Group IV: SAGE-324 Matched Placebo Placebo Group 1 Intervention

Participants will receive SAGE-324 matched placebo, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324 matched placebo, oral tablets, once daily (QD), in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324 matched placebo, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 milligrams (mg) of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

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

Biogen

Industry Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Citations

1. investors.biogen.com investors.biogen.com/news-releases/news-release-details/sage-therapeutics-and-biogen-announce-topline-results-phase-2

Sage Therapeutics and Biogen Announce Topline Results ... SAGE-324 (BIIB124) did not demonstrate a statistically significant dose-response relationship on the primary endpoint in participants with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05173012

Study to Evaluate SAGE-324 in Participants With Essential ... The primary purpose of this study is to evaluate the dose-response relationship of different doses of SAGE-324 on upper extremity tremor in ...

3. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29731

A Randomized Phase 2 KINETIC Trial Evaluating SAGE‐324 ... A double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET).

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/sage-biogen-tremor-trial/

Sage-Biogen's SAGE-324 shows no benefit in essential ... Sage and Biogen disclosed results from a Phase II study where SAGE-324 showed no significant benefit in treating essential tremors.

5. investor.sagerx.com investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-and-biogen-announce-sage-324-phase-2-placebo

Investors & Media The study (n=67 full analysis set) achieved its primary endpoint of a statistically significant reduction from baseline compared to placebo.