Valbenazine for Schizophrenia

No longer recruiting at 80 trial locations

Overseen By Neurocrine Medical Information Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Neurocrine Biosciences

Must be taking: Antipsychotics

Must not be taking: VMAT2 inhibitors

Disqualifiers: Pregnancy, Depression, Substance use, others

Stay on Your Current Meds You can continue your current medications while participating

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: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether valbenazine can reduce symptoms in people with schizophrenia who aren't improving enough with their current antipsychotic medications. Participants will receive either valbenazine, which affects brain chemicals, or a placebo. Those with a confirmed schizophrenia diagnosis for at least a year and on a stable antipsychotic treatment might be suitable candidates. The trial aims to determine if adding valbenazine can improve symptoms like delusions and hallucinations. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for this trial?

The trial does not specify that you need to stop taking your current medications. In fact, you must be on a stable regimen of antipsychotic medication to participate.

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

Research has shown that valbenazine is generally safe for use. In earlier studies, adults who took valbenazine for up to 48 weeks mostly found it safe, though some experienced side effects. Serious side effects occurred in about 12.6% of participants, and 13.6% stopped taking it due to these effects. These findings suggest that many can use valbenazine without major issues. The FDA has already approved valbenazine for another condition, which adds confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Valbenazine is unique because it targets the vesicular monoamine transporter 2 (VMAT2), which is different from typical antipsychotics that primarily focus on dopamine receptors. This novel mechanism may offer a fresh approach to managing symptoms of schizophrenia, potentially reducing side effects common with existing treatments like extrapyramidal symptoms. Researchers are excited about Valbenazine because it could provide a more targeted and potentially more tolerable option for individuals with schizophrenia.

What evidence suggests that valbenazine might be an effective treatment for schizophrenia?

Research has shown that valbenazine, which participants in this trial may receive, may help improve symptoms in people with tardive dyskinesia (TD), a movement disorder often found in those with schizophrenia. In earlier studies, patients taking valbenazine experienced noticeable improvements over time, with some even seeing their symptoms disappear. Specifically, one study found that 58.6% of patients taking a 40mg dose and 59.5% taking an 80mg dose had their symptoms go away. These results suggest that valbenazine could help manage symptoms of schizophrenia when standard treatments aren't enough. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Development Lead

Principal Investigator

Neurocrine Biosciences

Are You a Good Fit for This Trial?

This trial is for individuals aged 13 or older with a medically confirmed diagnosis of schizophrenia for at least one year. They must be on stable antipsychotic medication and not responding adequately to treatment. Participants need an adult informant and agree to use contraception. Excluded are those pregnant, breastfeeding, resistant to treatments, recently suicidal, or with severe substance disorders.

Inclusion Criteria

The participant must have an adult informant (for example, a family member, relative, partner, social worker, caseworker, residential facility staff, or nurse).

My antipsychotic medication dose has not changed recently.

My symptoms are stable and I am not hospitalized.

Exclusion Criteria

You have been diagnosed with schizophrenia that does not respond well to treatment.

Pregnant or breastfeeding or plans to become pregnant during the study. This criterion must be reconfirmed prior to the first dose of study treatment on Day 1.

You have had thoughts of hurting yourself or have attempted suicide in the past 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive valbenazine or placebo once daily as adjunctive treatment for schizophrenia

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Valbenazine

Trial Overview The Journey Study tests Valbenazine as an additional treatment against a placebo in people with schizophrenia who aren't fully helped by their current antipsychotics. The goal is to see if Valbenazine can better alleviate symptoms when used alongside standard medications.

How Is the Trial Designed?

Group I: Vesicular monoamine transporter 2 (VMAT2) inhibitor Experimental Treatment 1 Intervention

Valbenazine once daily

Group II: Placebo Placebo Group 1 Intervention

Placebo once daily.

Who Is Running the Clinical Trial?

Neurocrine Biosciences

Lead 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

The review highlights seven antipsychotic drugs in premarketing development, noting that Asenapine may improve negative and cognitive symptoms of schizophrenia, while Bifeprunox shows potential safety advantages despite a less convincing efficacy profile.

Olanzapine pamoate depot injection has comparable efficacy to oral olanzapine but raises significant safety concerns due to risks of inadvertent intravascular injection, leading to severe side effects like excessive sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. Bishara, D., Taylor, D.[2018]

In a review of 23 short-term placebo-controlled trials involving 7553 patients with schizophrenia, the risk of death was found to be significantly higher in the placebo group compared to those receiving active treatment, with a crude odds ratio of 7.92, indicating a potential safety concern with placebo use.

Despite the higher mortality risk associated with placebo, the study emphasizes the necessity of short-term placebo-controlled trials to ensure that new antipsychotic drugs are effective and safe before they are licensed for use, suggesting that without such trials, ineffective drugs could be approved and cause harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risk of death among adult participants in trials of antipsychotic drugs in schizophrenia. Isaac, M., Koch, A.[2010]

In a study of 450 patients with schizophrenia receiving placebo injections, a 10%-15% reduction in the PANSS total score after the first week was found to be a strong predictor of long-term response at week 9, indicating that early improvements can help identify potential placebo responders.

Patients with better judgment and insight at baseline (lower PANSS G12 scores) were also more likely to show a placebo response, suggesting that certain demographic and clinical characteristics may influence the effectiveness of placebo treatments in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Placebo Improvement Is a Marker for Subsequent Placebo Response in Long-Acting Injectable Antipsychotic Trials for Schizophrenia: Combined Analysis of 4 RCTs. Kumagai, F., Suzuki, T., Fleischhacker, WW., et al.[2019]

In a pooled analysis of two 6-week trials involving 422 patients with schizophrenia, early response to antipsychotic treatment (low-dose olanzapine or haloperidol) significantly distinguished active drug from placebo, with a greater mean reduction in psychiatric symptoms observed at 2 weeks.

The study suggests that shortening the duration of placebo-controlled trials from 6 weeks to 2-4 weeks is feasible for identifying efficacy in acutely ill patients, as early treatment response was predictive of overall treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials. Kinon, BJ., Chen, L., Stauffer, VL., et al.[2021]

In a 6-month study involving 5134 patients with paranoid schizophrenia, risperidone long-acting injectable (RLAI) demonstrated significant improvements in both clinical severity and patient functioning, indicating its efficacy in routine clinical practice.

The treatment was generally well-tolerated, with 20% of patients experiencing treatment-emergent adverse events, the most common being akathisia and weight gain, but overall, the study confirmed RLAI's good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders. Parellada, E., Kouniakis, F., Siurkute, A., et al.[2019]

In a double-blind study involving 16 patients with schizophrenia and negative symptoms, deprenyl (15 mg/day) did not provide a significant therapeutic benefit compared to placebo over 8 weeks.

Both groups experienced a slight improvement, but this was likely due to a placebo effect, as the benefits disappeared after stopping the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deprenyl augmentation for treating negative symptoms of schizophrenia: a double-blind, controlled study. Jungerman, T., Rabinowitz, D., Klein, E.[2019]

In a meta-regression of 167 trials involving 28,102 participants, factors such as larger sample sizes and younger mean participant age were found to significantly influence the degree of placebo response in antipsychotic drug trials for schizophrenia.

The study revealed that while several design and patient-related factors affect placebo response, only sample size and participant age were significant in multivariable analysis, indicating that understanding these factors is crucial for interpreting drug efficacy in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

60 years of placebo-controlled antipsychotic drug trials in acute schizophrenia: Meta-regression of predictors of placebo response. Leucht, S., Chaimani, A., Leucht, C., et al.[2019]

Antipsychotic drugs significantly reduce relapse rates in patients with schizophrenia, with a 1-year relapse rate of 27% for those on medication compared to 64% for those on placebo, indicating a strong efficacy (risk ratio 0.40).

While antipsychotic treatment improves relapse prevention and may enhance quality of life, it is associated with side effects such as weight gain (10% vs 6%) and movement disorders (16% vs 9%), highlighting the need to balance benefits against potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Leucht, S., Tardy, M., Komossa, K., et al.[2022]

In a study of 672 patients with schizophrenia, early improvement in symptoms (measured by a 10% reduction in PANSS score at week 1) was strongly predictive of a subsequent placebo response by week 6.

Lower baseline scores for disorganized thoughts also correlated with a higher likelihood of responding to placebo, suggesting that these factors can help identify potential placebo responders early in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo effects in adult and adolescent patients with schizophrenia: combined analysis of nine RCTs. Kubo, K., Fleischhacker, WW., Suzuki, T., et al.[2020]

In a meta-regression analysis of 18 double-blind, randomized, placebo-controlled trials involving 998 patients with stable schizophrenia, drugs were found to be more effective than placebo in reducing negative symptoms, although the effect size was small (Cohen's d: 0.208).

The study revealed a significant placebo response (Cohen's d: 2.909), indicating that factors like the number of trial arms, study sites, and industry sponsorship can influence the placebo effect, suggesting a need for improved trial designs to accurately assess treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Placebo Response in Pharmacological Clinical Trials of Negative Symptoms in Schizophrenia: A Meta-regression Analysis. Fraguas, D., Díaz-Caneja, CM., Pina-Camacho, L., et al.[2022]

In a study of 292 severely ill schizophrenia patients, both paliperidone palmitate (PP) and oral risperidone showed significant improvement in symptoms as measured by the PANSS scale by day 4, with PP demonstrating a greater reduction in symptoms at this early time point.

Paliperidone palmitate was associated with a higher percentage of patients achieving a 30% reduction in PANSS scores compared to oral risperidone at days 15 and 22, indicating its potential for more effective symptom management in the longer term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paliperidone palmitate versus risperidone long-acting injection in markedly-to-severely ill schizophrenia subjects: onset of efficacy with recommended initiation regimens. Fu, DJ., Bossie, CA., Kern Sliwa, J., et al.[2015]

Second-generation antipsychotic long-acting injections (SGA-LAIs) generally have safety profiles similar to their oral counterparts, but they also present new safety concerns, such as the risk of postinjection syndrome and worsening psychosis, particularly with olanzapine-LAI.

The review highlighted serious risks associated with risperidone-LAI and paliperidone palmitate, including worsening psychotic symptoms and a concerning link to increased suicide rates, emphasizing the need for further research to clarify these safety signals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects associated with second-generation antipsychotic long-acting injection treatment: a comprehensive systematic review. Gentile, S.[2018]

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. clinicaltrialsarena.com clinicaltrialsarena.com/news/neurocrine-biosciences-debuts-new-data-for-effectiveness-of-ingrezza/

Neurocrine Biosciences debuts new data for effectiveness ... Of those who completed the trial, 58.6% of patients on 40mg reached remission while the 80mg group saw 59.5% doing the same. Results from the ...

3. 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.

4. prnewswire.com prnewswire.com/news-releases/neurocrine-biosciences-presents-48-week-remission-data-on-treatment-of-tardive-dyskinesia-with-ingrezza-valbenazine-capsules-302406507.html

Neurocrine Biosciences Presents 48-Week Remission ... Participants experienced TD improvements during long-term treatment as demonstrated by mean change from baseline to Week 48 in AIMS total score ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05110157

NCT05110157 | Journey Study: Evaluate the Efficacy, ... The primary objective for this study is to evaluate the effect of adjunctive valbenazine versus placebo on symptoms of schizophrenia in participants who have ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/209241Orig1s016.pdf

CENTER FOR DRUG EVALUATION AND RESEARCH The safety of INGREZZA was evaluated in 3 placebo-controlled studies, each 6 weeks in duration (fixed dose, dose escalation, dose reduction), ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28839341/

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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02405091

NCT02405091 | Safety and Tolerability Study of NBI-98854 ... Phase 3, open-label, study to evaluate the safety and tolerability of NBI-98854 administered once daily (qd) for a total of 48 weeks of treatment.

9. neurology.org neurology.org/doi/10.1212/WNL.88.16_supplement.P2.017

Safety and Tolerability of Valbenazine (NBI-98854) in ... Serious TEAEs were reported in 12.6% of subjects; TEAEs led to dose reduction in 6.1% of subjects and discontinuation in 13.6% of subjects.

10. 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 ( ...