SchizophreniaPhase 1NCT03669250
CVN058 Effect on Mismatch Negativity in Schizophrenics
A Phase 1 study testing CVN058 in people with Schizophrenia, run by Cerevance Alpha, Inc. at 3 sites in United States.
Trial summary
This is a phase 1, double-blind, placebo-controlled, 3 period cross-over study to evaluate CVN058 target engagement by measuring auditory evoked potential mismatch negativity (MMN) downstream to 5-hydroxytryptamine receptor 3 (5-HT3) as a pharmacodynamic (PD) marker. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- CVN058
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 3 sitesUnited States
- Study dates
- 9 Nov 2018to 6 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects 18 to 50 years of age, inclusive, at the time of informed consent.
- The subject weighs at least 50 kg and has a body mass index (BMI) between 18 and 40 kg/m2 inclusive at Screening.
- Subject meets schizophrenia criteria as defined by the Diagnostic \& Statistical Manual of mental Disorders, 5th Edition (DSM-V).
- Subjects are on a stable dose of antipsychotic medication(s) for at least 2 months prior to - Screening as documented by medical history and assessed by site staff.
- Subject has a Positive and Negative Syndrome Scale (PANSS) total score of <95.
Who cannot join
- Subject currently receiving treatment with any excluded medication or dietary supplement.
- Subjects who have a history of gastrointestinal disease that would influence the absorption of study drug or have a history of any surgical intervention known to impact absorption (e.g., bariatric surgery or bowel resection).
- Subjects having clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis) outside the reference range for the testing laboratory, unless the results are deemed to be not clinically significant (NCS) by the investigator at Screening.
- Subjects with moderate to severe substance use disorder, unstable mood or anxiety disorder.
- Subject has a current diagnosis of a significant psychiatric illness other than schizophrenia per DSM-V and is in an acute phase/episode.
- Subject has clinically meaningful hearing loss.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
New York State Psychiatric Institute
New York, New York, 10032
Nathan Kline Institute
New York, New York, 10962
About this study
Official title: A Placebo-Controlled Study to Evaluate the Effect of a Single Dose of CVN058 on Mismatch Negativity in Subjects With Stable Schizophrenia
This is a phase 1, double-blind, placebo-controlled, 3 period cross-over study to evaluate CVN058 target engagement by measuring auditory evoked potential mismatch negativity (MMN) downstream to 5-hydroxytryptamine receptor 3 (5-HT3) as a pharmacodynamic (PD) marker.
Read the detailed description
Male and female subjects with schizophrenia, age 18 to 50 years old, inclusive, will be randomized to 1 of 6 treatment sequences (Table 2.a) to receive 1 of 3 dose regimens in each period: a single oral administration of CVN058 (15 mg or 150 mg) or matching placebo. The sequence will determine the order in which a subject will take each of the 3 regimens. Discontinued subjects may be replaced at the discretion of the sponsor so that approximately 20 completed subjects are available for analysis.
The study includes three 1-day treatment periods, with a minimum of 7-day washout, maximum 10 day washout (2 total washouts, after Periods 1 and 2) between periods, and a 7-10 day follow-up call post dosing of the last period. Subjects may be inpatients or outpatients at the discretion of the Investigator.
- Conditions
- Schizophrenia
- Being tested
- CVN058, Placebo comparator
- Keywords
- MMN, EEG, P50, gamma power, P300, auditory gating
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CVN058Drug
Also called TAK058
CVN058 will be given at two doses, a low does and a high dose
Placebo comparatorOther
inactive placebo
| Study group | Role | What they receive |
|---|---|---|
| CVN058, low dose | Active comparator | CVN058 prepared in concentrations of 10mg/mL, and are compounded by the clinical site. Subjects will receive one dose of CVN058 at 15mg or 75mg substitution of 15mg. Receives: Drug: CVN058 |
| CVN058, high dose | Active comparator | CVN058 prepared in concentrations of 10mg/mL, and are compounded by the clinical site. Subjects will receive one dose of CVN058 at 150mg. Receives: Drug: CVN058 |
| Placebo | Placebo comparator | Matching placebo. Receives: Other: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Amplitude of Duration of Auditory Mismatch Negativity (MMN) by Dose Level
MMN is a pre-attentive auditory component elicited by deviant stimuli in an auditory oddball task. Participants were repeatedly exposed to auditory tones and a small proportion of those tones (the "deviant" stimuli) differ from the others (the "standard" stimuli) in their frequency or duration. Typically, the tones are presented, and the evoked potentials are recorded while participants are engaged on a different task, such as reading. Normally, the occurrence of a deviant stimulus increases the amplitude of the negative component in the evoked potential occurring at around 200 msec. MMN is the difference in amplitude between deviant and standard stimuli responses and considered to represent an aspect of pre-attentive novelty detection.
Measured: 1.5 hours post-dose on Day 1
Secondary outcomes (1)
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. TEAEs are defined as any event with onset during or after the first dose of study treatment (active or placebo)
Measured: Screening through 30 days post-dose, up to 58 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2018
- Study start9 Nov 2018
- Primary completion6 Mar 2020
- Study completion6 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Male and female subjects with schizophrenia, age 18 to 50 years old, inclusive, will be randomized to 1 of 6 treatment sequences to receive 1 of 3 dose regimens in each period; a single oral administration of CVN058, or a matching placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerevance Alpha, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Susan Kapurch, Study chair, Cerevance, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03669250
- Sponsor's protocol ID
- CVN058-103
- Status last verified
- Jul 2024
- First submitted
- 4 Sep 2018
- Last updated
- 4 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled Study to Evaluate the Effect of a Single Dose of CVN058 on Mismatch Negativity in Subjects With Stable Schizophrenia
- ClinicalTrials.gov ID
- NCT03669250
- Acronym / sponsor ID
- CVN058-103
- Conditions
- Schizophrenia
- Keywords
- MMN, EEG, P50, gamma power, P300, auditory gating
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Cerevance Alpha, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Nov 2018 (actual)
- Primary completion
- 6 Mar 2020 (actual)
- Study completion
- 6 Mar 2020 (actual)
- First posted
- 13 Sep 2018 (actual)
- Results
- Posted 4 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1, double-blind, placebo-controlled, 3 period cross-over study to evaluate CVN058 target engagement by measuring auditory evoked potential mismatch negativity (MMN) downstream to 5-hydroxytryptamine receptor 3 (5-HT3) as a pharmacodynamic (PD) marker.
Detailed description
Male and female subjects with schizophrenia, age 18 to 50 years old, inclusive, will be randomized to 1 of 6 treatment sequences (Table 2.a) to receive 1 of 3 dose regimens in each period: a single oral administration of CVN058 (15 mg or 150 mg) or matching placebo. The sequence will determine the order in which a subject will take each of the 3 regimens. Discontinued subjects may be replaced at the discretion of the sponsor so that approximately 20 completed subjects are available for analysis.
The study includes three 1-day treatment periods, with a minimum of 7-day washout, maximum 10 day washout (2 total washouts, after Periods 1 and 2) between periods, and a 7-10 day follow-up call post dosing of the last period. Subjects may be inpatients or outpatients at the discretion of the Investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Male and female subjects with schizophrenia, age 18 to 50 years old, inclusive, will be randomized to 1 of 6 treatment sequences to receive 1 of 3 dose regimens in each period; a single oral administration of CVN058, or a matching placebo.
| Arm | Type | Receives |
|---|---|---|
| CVN058, low dose | Active comparator | Drug: CVN058CVN058 prepared in concentrations of 10mg/mL, and are compounded by the clinical site. Subjects will receive one dose of CVN058 at 15mg or 75mg substitution of 15mg. |
| CVN058, high dose | Active comparator | Drug: CVN058CVN058 prepared in concentrations of 10mg/mL, and are compounded by the clinical site. Subjects will receive one dose of CVN058 at 150mg. |
| Placebo | Placebo comparator | Other: Placebo comparatorMatching placebo. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Subjects 18 to 50 years of age, inclusive, at the time of informed consent.
- The subject weighs at least 50 kg and has a body mass index (BMI) between 18 and 40 kg/m2 inclusive at Screening.
- Subject meets schizophrenia criteria as defined by the Diagnostic \& Statistical Manual of mental Disorders, 5th Edition (DSM-V).
- Subjects are on a stable dose of antipsychotic medication(s) for at least 2 months prior to - Screening as documented by medical history and assessed by site staff.
- Subject has a Positive and Negative Syndrome Scale (PANSS) total score of <95.
Key exclusion criteria (6 listed)
- Subject currently receiving treatment with any excluded medication or dietary supplement.
- Subjects who have a history of gastrointestinal disease that would influence the absorption of study drug or have a history of any surgical intervention known to impact absorption (e.g., bariatric surgery or bowel resection).
- Subjects having clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis) outside the reference range for the testing laboratory, unless the results are deemed to be not clinically significant (NCS) by the investigator at Screening.
- Subjects with moderate to severe substance use disorder, unstable mood or anxiety disorder.
- Subject has a current diagnosis of a significant psychiatric illness other than schizophrenia per DSM-V and is in an acute phase/episode.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CVN058Also: TAK058CVN058 will be given at two doses, a low does and a high dose | Drug | CVN058, high dose, CVN058, low dose |
| Placebo comparatorinactive placebo | Other | Placebo |
Primary outcome
Mean Amplitude of Duration of Auditory Mismatch Negativity (MMN) by Dose Level
Time frame: 1.5 hours post-dose on Day 1
MMN is a pre-attentive auditory component elicited by deviant stimuli in an auditory oddball task. Participants were repeatedly exposed to auditory tones and a small proportion of those tones (the "deviant" stimuli) differ from the others (the "standard" stimuli) in their frequency or duration. Typically, the tones are presented, and the evoked potentials are recorded while participants are engaged on a different task, such as reading. Normally, the occurrence of a deviant stimulus increases the amplitude of the negative component in the evoked potential occurring at around 200 msec. MMN is the difference in amplitude between deviant and standard stimuli responses and considered to represent an aspect of pre-attentive novelty detection.
1 secondary outcome
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Screening through 30 days post-dose, up to 58 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Kapurch study chair
Cerevance, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CVN058 in people with Schizophrenia, run by Cerevance Alpha, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Amplitude of Duration of Auditory Mismatch Negativity (MMN) by Dose Level (time frame: 1.5 hours post-dose on Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2024.