Valbenazine for Tardive Dyskinesia

Overseen By John M de Figueiredo,, MD, ScD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: CYP3A4 inducers, Dopamine agonists

Disqualifiers: Unstable psychiatric status, Cognitive impairment, Substance use disorder, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how Valbenazine, a medication, can help those suffering from tardive dyskinesia, a condition causing involuntary, repetitive movements due to long-term use of certain mental health medications. Researchers seek to determine if Valbenazine not only improves the physical symptoms but also reduces feelings of demoralization, anxiety, and depression. Individuals experiencing these involuntary movements from medication for at least a few weeks might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including strong CYP3A4 inducers, dopamine agonists, MAO inhibitors, stimulants, and VMAT2 inhibitors.

Is there any evidence suggesting that Valbenazine is likely to be safe for humans?

Research has shown that Valbenazine is generally safe for people with tardive dyskinesia. In one study, adults who took Valbenazine for up to 48 weeks tolerated it well. The most common side effects included sleepiness and fatigue. Another study found that older adults experienced significant symptom improvements within eight weeks, with no new safety concerns. Overall, previous research has demonstrated Valbenazine's good safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Valbenazine is unique because it specifically targets the underlying neurological causes of tardive dyskinesia by inhibiting the vesicular monoamine transporter 2 (VMAT2). This mechanism is different from traditional treatments like anticholinergics or benzodiazepines, which primarily focus on managing symptoms rather than addressing the root cause. Researchers are excited about Valbenazine because it offers a more precise approach, potentially leading to better management of involuntary movements with fewer side effects. Additionally, its targeted action could mean improved outcomes for patients who have not found relief with existing therapies.

What evidence suggests that Valbenazine might be an effective treatment for Tardive Dyskinesia?

Research has shown that Valbenazine effectively treats tardive dyskinesia (TD). Many patients experience symptom improvement, with one study finding that 59.2% of participants showed better results after 48 weeks. Other studies report significant improvements in the physical, social, and emotional well-being of people with TD. These findings suggest that Valbenazine can provide lasting and meaningful relief from TD symptoms. Overall, the evidence supports Valbenazine as a promising option for managing tardive dyskinesia. ^{5 6 7 8 9}

Who Is on the Research Team?

John De Figueiredo, MD

Principal Investigator

Clinical Professor of Psychiatry

Are You a Good Fit for This Trial?

This trial is for individuals aged 26-84 who have been diagnosed with tardive dyskinesia, a condition causing involuntary movements, as a result of taking neuroleptic medications. Both males and females are eligible if they meet the DSM-5 criteria for this condition.

Inclusion Criteria

I am between 26 and 84 years old.

My gender does not affect my eligibility.

I have involuntary movements due to medication for mental health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Valbenazine and are assessed with various scales to measure demoralization, anxiety, depression, and subjective incompetence every two weeks

6 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Valbenazine

Trial Overview The study is testing whether Valbenazine can help reduce feelings of demoralization in patients with tardive dyskinesia by treating their symptoms. It's a preliminary step to see if it's worth doing larger studies on this potential treatment.

How Is the Trial Designed?

Group I: Valbenazine Experimental Treatment 1 Intervention

All participants will be treated with Valbenazine for 6 weeks.

Valbenazine is already approved in United States for the following indications:

Approved in United States as Ingrezza for:

• Tardive dyskinesia
• Chorea associated with Huntington's disease

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Neurocrine Biosciences

Industry Sponsor

Trials

78

Recruited

6,600+

Kyle W. Gano

Neurocrine Biosciences

Chief Executive Officer since 2024

PhD in Pharmacology

Dr. Sanjay Keswani

Neurocrine Biosciences

Chief Medical Officer

MD

Published Research Related to This Trial

Valbenazine (VBZ) significantly improved tardive dyskinesia (TD) symptoms in subjects with schizophrenia or mood disorders over a treatment period of up to 48 weeks, with greater improvements observed at higher doses (80 mg) compared to placebo.

After stopping VBZ treatment, TD symptoms began to return toward baseline levels, indicating that while VBZ is effective for long-term management of TD, its effects diminish after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder. Kane, JM., Correll, CU., Liang, GS., et al.[2022]

Valbenazine, a VMAT2 inhibitor, is the first FDA-approved medication specifically for treating tardive dyskinesia (TD), showing effective results in a case study of a 49-year-old woman with severe TD symptoms.

In a phase III clinical trial, the once-daily dose of 80 mg of valbenazine was found to be both effective and safe for managing TD, even in a patient with a complex medical history and rapid onset of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Severe Tardive Dyskinesia with Valbenazine, Including a Patient's Perspective. Josiassen, RC., Filmyer, DM., Gillean, J., et al.[2019]

In a 6-week phase 3 trial involving 225 participants with moderate to severe tardive dyskinesia, valbenazine at 80 mg/day significantly reduced dyskinesia symptoms compared to placebo, with a mean change of -3.2 on the Abnormal Involuntary Movement Scale (AIMS).

Valbenazine was generally well tolerated, with a safety profile consistent with previous studies, and did not negatively impact psychiatric status, indicating its potential as a safe treatment option for tardive dyskinesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Hauser, RA., Factor, SA., Marder, SR., et al.[2022]

Valbenazine (Ingrezza) is the first medication approved by the FDA specifically for treating tardive dyskinesia, a condition characterized by involuntary movements often caused by long-term use of antipsychotic medications.

This approval marks a significant advancement in the management of tardive dyskinesia, providing patients with a targeted treatment option to help alleviate their symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine (Ingrezza): The First FDA-Approved Treatment for Tardive Dyskinesia. Uhlyar, S., Rey, JA.[2020]

Valbenazine is the first FDA-approved medication specifically for treating tardive dyskinesia (TD), showing significant improvement in symptoms at a dose of 80 mg/day with a clinically meaningful effect size of 0.90 in short-term trials.

Compared to tetrabenazine, valbenazine offers advantages such as once-a-day dosing and a better short-term side effect profile, although further long-term studies are needed to fully understand its benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine for Tardive Dyskinesia. Freudenreich, O., Remington, G.[2022]

Valbenazine (VBZ) significantly improved tardive dyskinesia (TD) symptoms in subjects with mood disorders over a 48-week treatment period, with greater improvements observed at higher doses compared to placebo, indicating its efficacy as a treatment option.

After stopping VBZ treatment, TD symptoms began to return toward baseline levels, suggesting that while VBZ is effective in managing TD, ongoing treatment may be necessary to maintain symptom control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder. Correll, CU., Josiassen, RC., Liang, GS., et al.[2022]

Valbenazine (Ingrezza™) is an approved treatment for tardive dyskinesia (TD) in adults, demonstrating its efficacy as a selective VMAT2 inhibitor for managing this condition.

The drug is also being explored for Tourette syndrome in phase 2 trials, indicating its potential for treating various central nervous system disorders beyond TD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine: First Global Approval. Kim, ES.[2018]

Valbenazine is a selective VMAT2 inhibitor that effectively modulates dopamine release, showing significant improvement in symptoms of tardive dyskinesia (TD) in clinical trials.

As there are currently no FDA-approved treatments for TD, valbenazine represents a promising new option, with a new drug application submitted for priority review in 2016.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine for the treatment of tardive dyskinesia. Barquero, N.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5546553/

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with ... Sustained TD improvements were found in subjects with SCHZ who received up to 48 weeks of VBZ, with TD reverting toward baseline when assessed 4 weeks after ...

2. neurocrine.gcs-web.com neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-presents-new-data-ingrezzar-valbenazine

Neurocrine Biosciences Presents New Data on INGREZZA ... Treatment with INGREZZA resulted in tardive dyskinesia (TD) symptom remission for the majority of patients at Week 48: 59.2% (61/103) of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05859698?term=VALBENAZINE&rank=5

NCT05859698 | Study of the Effectiveness of Valbenazine ... This study will evaluate the effectiveness of valbenazine on patient- and clinician-reported outcomes assessing health-related quality of life, functioning, and ...

4. neurologylive.com neurologylive.com/view/valbenazine-linked-to-better-physical-emotional-well-being-tardive-dyskinesia

Valbenazine Linked to Better Physical and Emotional Well ... Valbenazine significantly improved physical, social, and emotional outcomes in tardive dyskinesia patients, as shown in the KINECT-PRO phase 4 ...

5. ingrezzahcp.com ingrezzahcp.com/efficacy/tardive-dyskinesia

TD Efficacy | INGREZZA® (valbenazine) capsules Efficacy in adults with tardive dyskinesia · Rapid, robust results. · Sustained reductions. · Clinically meaningful improvements—early and over time · More than ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5546552/

Long-Term Safety and Tolerability of Valbenazine (NBI- ... Conclusion. Valbenazine appeared to be well tolerated in adults with TD who received up to 48 weeks of treatment. In addition to long-term efficacy results ( ...

7. neurocrine.gcs-web.com neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-reports-patient-reported-outcome-data

Significant and Clinically Meaningful Improvements in ... The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with tardive dyskinesia are sleepiness and tiredness. The most ...

8. ingrezzahcp.com ingrezzahcp.com/efficacy/patient-reported-outcomes

Patient-reported outcomes in tardive dyskinesia Learn about the KINECT-PRO study design and patient reported outcomes with TD Impact Scale. See Prescribing Info, including Boxed Warning.

9. prnewswire.com prnewswire.com/news-releases/neurocrine-biosciences-publishes-analysis-showing-long-term-efficacy-and-a-consistent-safety-profile-of-ingrezza-valbenazine-capsules-in-older-adults-with-tardive-dyskinesia-in-the-journal-of-clinical-psychiatry-302437764.html

Neurocrine Biosciences Publishes Analysis Showing Long ... These data show that participants 65 years and older achieved clinically meaningful improvements in tardive dyskinesia symptoms within eight weeks of INGREZZA ...