CVN058 Effect on Mismatch Negativity in Schizophrenics

NCT03669250 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CVN058-103
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Schizophrenia

Keywords

MMN; EEG; P50; gamma power; P300; auditory gating

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  Screening through 30 days post-dose, up to 58 days

Study Arms (3)

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.

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.

Drug: CVN058

Placebo

PLACEBO COMPARATOR

Matching placebo.

Other: Placebo comparator

Interventions

CVN058 DRUG

CVN058 will be given at two doses, a low does and a high dose

Also known as: TAK058

CVN058, high dose; CVN058, low dose

Placebo comparator OTHER

inactive placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cerevance Alpha, Inc.: lead

Study Sites (3)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Nathan Kline Institute

New York, New York, 10962, United States

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Michelle Charles, Executive Director Regulatory Affairs
• Organization: Cerevance

michelle.charles@cerevance.com

(408) 220-5722

Study Officials

• Susan Kapurch

  Cerevance, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind, placebo controlled.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 13, 2018
• Study Start: November 9, 2018
• Primary Completion: March 6, 2020
• Study Completion: March 6, 2020
• Last Updated: October 4, 2024
• Results First Posted: October 4, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)