Study to Evaluate the Efficacy, Safety, and Tolerability of Valbenazine as Adjunctive Treatment in Subjects with Schizophrenia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Neurocrine Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04]

Trial duration

30 Sep 2022 → 18 Feb 2025

Decision date (initial)

2024-03-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Neurocrine Biosciences, Inc.

External identifiers

EU CT number

2023-508433-14-00

EudraCT number

2021-003714-39

ClinicalTrials.gov

NCT05110157

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacokinetic

To evaluate the effect of adjunctive valbenazine versus placebo on symptoms of schizophrenia in subjects who have inadequate response to
antipsychotic treatment.

Secondary objectives 2

1. Evaluate the effect of adjunctive valbenazine versus placebo on illness severity and subject functioning in subjects who have inadequate response to antipsychotic treatment
2. Evaluate the safety and tolerability of valbenazine as adjunctive treatment in subjects who have inadequate response to antipsychotic treatment

Conditions and MedDRA coding

Schizophrenia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Completed written informed consent in accordance with the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and according to local laws and regulations.
2. At the time of signing the informed consent subject must be ≥18 years of age.
3. Medically confirmed diagnosis of schizophrenia as defined by the DSM-5 and confirmed by the MINI for Psychotic Disorders Version 7.0.2.
4. The initial diagnosis of schizophrenia must be ≥1 year before the screening visit.
5. The subject is receiving background antipsychotic therapy (other than clozapine) at a total daily dose between 3 mg and 8 mg of risperidone equivalents
6. Plasma levels for at least 1 of the subject's antipsychotic medications must be detectable by an available assay.
7. The subject is treated with a stable regimen antipsychotic medication.
8. Must meet all of the following criteria at screening visit (Visit 1) and Day 1 (Visit 2): • Positive and Negative Syndrome Scale (PANSS) total score ≥70 • PANSS score of ≥4 on at least 1 of the following: - P1 (delusions) - P3 (hallucinations) - P6 (suspiciousness) - G9 (unusual thought content) • Clinical Global Impression of Severity (CGI S) score ≥ 4 • Stable background antipsychotic medication dose between the screening visit and Day 1 • Stable PANSS total score between the screening visit and Day 1
9. The subject is outpatient with stable symptomatology
10. The subject's diagnosis, background antipsychotic therapy, and severity of symptoms must be confirmed by the Sponsor or designee prior to the first dose of study treatment on Day 1.
11. The subject must have an adult informant (eg, a family member, relative, partner, social worker, caseworker, residential facility staff, or nurse).
12. A body mass index (BMI) of 18.0 to 40.5 kg/m2 (inclusive) at the screening visit.
13. Female subjects of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at Day 1.
14. Female subjects of childbearing potential must agree to use contraception consistently from the screening visit until 30 days after the last dose of study drug or final study visit, whichever is longer.
15. Male subjects must agree to use contraception consistently from screening visit until 30 days after last dose of study treatment.
16. Willing to comply with all study procedures and restrictions; and in the opinion of the investigator, the subject is capable of understanding and complying with all study procedures and restrictions. This criterion must be reconfirmed before the first dose of study treatment on Day 1.

Exclusion criteria 23

1. Pregnant or breastfeeding or plans to become pregnant during the study. This criterion must be reconfirmed before the first dose of study treatment on Day 1.
2. Known hypersensitivity to any component of the formulation of valbenazine.
3. Have comorbid Parkinsonism or exhibit more than a minimal level of extrapyramidal sings/symptoms
4. Have a Barnes Akathisia Rating Scale (BARS) global clinical assessment score ≥2 at the screening visit (Visit 1). This criterion must be reconfirmed before the first dose of study treatment on Day 1.
5. Has history of treatment resistant schizophrenia.
6. Diagnosis of schizoaffective disorder; bipolar disorder; or a lifetime diagnosis of obsessive-compulsive disorder.
7. Recent (within the last 6 months before the screening visit) occurrence of panic disorder, depressive episode, or other comorbid psychiatric conditions currently requiring clinical attention.
8. Evidence of depression as measured by a Calgary Depression Scale for Schizophrenia (CDSS) score ≥11 at the screening visit or Day 1.
9. Initiation or changes in nonpharmacological psychosocial therapeutic treatment (eg, day hospital treatment, cognitive-behavioral therapy) within 3 weeks before the screening visit or expected to change throughout the length of the study.
10. Subjects with any suicidal behavior or suicidal ideation (Type 4 or 5) within 6 months before the screening visit or on Day 1.
11. Diagnosis of moderate or severe substance use disorder within the 6 months before the screening visit.
12. Positive alcohol test (value ≥0.020%) or urine drug screen for disallowed substances, including amphetamines; barbiturates; cocaine; marijuana; methadone; methamphetamine; 3,4methylenedioxymethamphetamine (MDMA); phencyclidine; or nonprescribed benzodiazepines or opiates.
13. Have a clinically significant unstable medical condition within 60 days before the screening visit in the judgement of the investigator or any laboratory value outside the normal range that is considered by the investigator to be clinically significant at the screening visit.
14. Have any known history of long QT syndrome or cardiac arrhythmia.
15. Have a triplicate average electrocardiogram (ECG) QT interval corrected for heart rate using Fridericia's formula (QTcF) of >450 msec (male subjects) or >470 msec (female subjects) or the presence of any clinically significant cardiac abnormality during the Screening Period.
16. Have a moderate or severe hepatic impairment or chronic elevation of any of the following laboratory tests: Serum creatinine, AST, ALT, GGT, Serum total bilirubin.
17. Laboratory abnormalities of Hemoglobin, White blood cell count, Platelet count or Absolute neutrophil count at the screening visit.
18. Have a hematologic malignancy or solid tumor diagnosed within 3 years before the screening visit or not in remission, with the exception of localized skin cancer or carcinoma in situ of the cervix that has been excised.
19. Have any known history of neuroleptic malignant syndrome.
20. Are currently taking any of the prohibited medications (as described in Section 7.1 of the protocol). Subjects who have received these medications in the past, must have been off them for at least 30 days before the screening visit.
21. Has previously been enrolled and received study treatment in this study (Study NBI-98854-ATS3019) or any other valbenazine clinical trial; has used any active investigational drug in the context of a clinical study within 30 days or 5 half-lives before the screening visit, whichever is longer; has participated in 3 or more clinical studies within 12 months prior before the screening visit; or is currently participating in another clinical study; or has participated in a clinical study for a psychiatric condition that is exclusionary in this protocol.
22. Prior (within 6 months of the screening visit) or concomitant use of any VMAT2 inhibitors.
23. Any reason that makes the subject unsuitable for participation in this study (eg, subject is homeless, known to have difficulty complying with treatment or medical procedures, known to provide inaccurate medical information, or attempt participation in clinical studies inappropriately).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in PANSS total score from baseline to Week 10.

Secondary endpoints 2

1. Change in CGI-S score from baseline to Week 10
2. Change in Personal and Social Performance Scale (PSP) score from baseline to Week 10

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Neurocrine Biosciences Inc.

Sponsor organisation

Neurocrine Biosciences Inc.

Address

12790 El Camino Real

City

San Diego

Postcode

92130-2008

Country

United States

Scientific contact point

Organisation

Neurocrine Biosciences Inc.

Contact name

Neurocrine Medical Information Call Center

Public contact point

Organisation

Neurocrine Biosciences Inc.

Contact name

Neurocrine Medical Information Call Center

Third parties 10

Locations

6 EU/EEA countries · 52 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 84 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications