Early Course Schizophrenia Spectrum DisorderPhase 2NCT04457310

A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia

A Phase 2 study testing CVL-562 (PF-06412562) 1 mg, CVL-562 (PF-06412562) 4 mg and CVL-562 (PF-06412562) 15 mg in people with Early Course Schizophrenia Spectrum Disorder, run by Yale University at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 45 years
Conditions the study is for: Early Course Schizophrenia Spectrum Disorder
What is being tested?: CVL-562 (PF-06412562) 1 mg, CVL-562 (PF-06412562) 4 mg and CVL-562 (PF-06412562) 15 mg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 112 participants
Where: 4 sitesUnited States
Study dates: 2 Mar 2021to 22 Mar 2024
Phase: Phase 2
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 45 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Between the ages of 18 (including 18 years of age) and 45 (up to 45 years and 11 months) at the time of baseline study visit.
Able to provide informed consent (as established by consent interview), and voluntary, signed informed consent prior to the performance of any study-specific procedures
Willing and able to perform study-relevant clinical assessments and Magnetic Resonance Imaging (MRI) as assessed by research staff.
Meet Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder on the basis of the Structured Clinical Interview for DSM-5 (SCID-5).
Be within 10 years of the onset of psychosis based on clinical assessment at the time of Visit 1.
Treatment seeking and willing to accept the constraints on treatment entailed by the study.

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Able to demonstrate a basic ability to follow spatial working memory task instructions and perform necessary related motor functions.
Demonstrate a premorbid IQ of ≥80 based on the Penn Reading Assessment (PRA). The PRA correlates with other measures of IQ including the Wide Range Achievement Test (WRAT), but is computerized, based in the laboratory of co-investigators Ruben C. Gur and Raquel E. Gur, and brief to administer, allowing us to lessen the assessment burden on an already lengthy first visit.
Be fluent in English as assessed by research staff.
Clinically stable treatment for at least two months prior to Visit 1 (no hospitalizations, or current suicidal/homicidal active ideation, intent, or plan).
On a stable psychotropic medication regimen (can include no psychotropic medications) for at least 3 weeks prior to Visit 1, and willing to maintain an unchanged regimen during the study. If on depot antipsychotics, participants must have stable dosing for at least two consecutive injections (including the most recent one) as the most recent injections. If on Invega Trinza, there must be no plans to change dosing during the course of the study.
For women of child bearing potential, no intention to become pregnant during the study period, and agreement to use a reliable method of birth control (e.g. Intra-Uterine Device (IUD), hormonal contraception, abstinence, condoms) during the study period. Women will be asked to continue their method of contraception for 1 month after receiving their final dose of medication. Any individual who becomes pregnant during the study will be immediately removed, and discussion of the risks and benefits of ongoing pharmacotherapy will proceed on purely clinical grounds.

Who cannot join

Any unstable medical, psychiatric, or neurological condition (including active or otherwise remarkable suicidal or homicidal ideation) that may necessitate urgent treatment. Active medical conditions that are minor or well controlled are not exclusionary if they do not affect risk to the patient, metabolism of study drug, or the study results (e.g. well-controlled type II diabetes or hypertension) as per the judgment of the investigator.
Be currently treated with any of the following: olanzapine, clozapine, ziprasidone or asenapine, in order to avoid prominent D1 receptor effects.
Any major neurological disease, brain injury, epilepsy, or history of severe head trauma, including concussion with loss of consciousness greater than or equal to > 15 minutes, or of psychosurgery.
History of significant cardiac disease (ex: ischemia, arrhythmia).
Any clinically significant abnormality on baseline medical screening tests (electrocardiogram (EKG), complete blood count with differential (CBC), complete metabolic profile (CMP).
Hepatitis B or C (by report or testing) in the presence of abnormal liver function tests

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Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (by report or by testing) due cognitive effects of HIV and AIDS.
Baseline EKG showing prolonged QTc interval (>450 for males, >470 for females, Framingham correction(3)), with repeat measurement showing the same abnormality.
Current mood episode meeting criteria for a major depressive episode or a manic or hypomanic episode.
History of electroconvulsive therapy (ECT) or treatment with neurostimulation in the past 6 months, or with plans to begin either such treatment during the study.
History of ADHD pre-morbid to the onset of psychosis or other psychiatric illnesses that may be accompanied by cognitive impairments.
Meeting SCID-5 moderate or severe substance use disorder for any substance other than nicotine within the 3 months prior to the initial assessment.
Positive urine toxicology testing for any substance other than marijuana or those prescribed for medical reasons at Visits 1-6.
Pregnancy or intention to become pregnant during the study.
Lactating/breast-feeding or intending to do so during the study
Any non-MRI compatible metal in the body or other contraindication to MR imaging. A copper IUD is allowable if permitted by local MRI practices.
Severe claustrophobia, back pain, morbid obesity, or other condition that may make an extended MR session difficult or lead to excessive movement during the imaging session.
Color blindness, strabismus or other uncorrectable visual problems. Those wearing glasses would be asked to use MRI-safe glasses.
Daily use of the following medication within 10 days prior to the initial visit or during the study: Long-acting nighttime or daytime gamma aminobutyric acid-A (GABA-A) receptor facilitators; anticonvulsant medications used at high doses or for seizure control, or psychostimulants or medical cannabis. Participants can be re-assessed for eligibility once they have been free of daily use of these medications for >10 days. Participants may take non-GABAergic sleep medications, short-acting GABA receptor facilitators (benzodiazepine, non-benzodiazepine) prior to and during the study.
Any change in type or dose of psychotropic medications within 3 weeks prior to initial visit or during study to avoid transient effects of medication regimen change. Medication type and dose will be carefully recorded and used as a covariate in analyses. Participants can be re-assessed for eligibility once they have been on a stable dose of medication for >3 weeks.
CVL-562 is metabolized by P450 CYP3A4. In order to avoid pharmacokinetic interactions, medications or substances that induce (barbiturate, carbamazepine, etc.) or are moderate-strong inhibitors (ketoconazole, etc.; grapefruit juice) are excluded if used within 10 days prior to or during study. Participants can be re-assessed for eligibility once they have been free of these medications/substances for >10 days.
Active attempts to discontinue smoking, vaping or other nicotine products within the 3 weeks prior to study or during the study. Participants can be re-assessed once quit attempt is stable.
Diastolic blood pressure >95 or <50 mmHg or systolic blood pressure > 170 or <80 mmHg with repeat measurement showing the same abnormality.
History of allergy or other contraindication to the proposed pharmacotherapy.
Other medication treatment with which proposed pharmacotherapy is contraindicated, in the opinion of study psychiatrists or of a subject's prescribing psychiatrist.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Yale University
New Haven, Connecticut, 06511
Columbia University
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Stony Brook University
Stony Brook, New York, 11794

Other trials in United States

About this study

This study will test whether CVL-562 (PF-06412562), a dopamine 1 partial agonist novel compound, affects working memory neural circuits in patients with early episode schizophrenia. The overall aim is to establish neuroimaging biomarkers of the Dopamine Receptor 1/Dopamine Receptor 5 Family (D1R/D5R) target engagement to accelerate development of D1R/D5R agonists in humans to treat cognitive impairments that underlie functional disability in schizophrenia, a key unaddressed clinical and public health concern.

Read the detailed description

This study proposes to examine the effects of CVL-562 (PF-06412562), a dopamine-1 receptor partial agonist, on the neural signal of brain regions involved in cognition in patients with schizophrenia and related psychotic disorders. The primary objective of this study is to understand the neural circuit targets of this compound as it relates to improving cognition in schizophrenia, using a spatial working memory task (sWM). The secondary objective will quantify dose-related drug effects on sWM precision based on behavioral data collected during scanning and examine effects on functional connectivity.

All patients will be psychiatrically stable with early course (psychotic symptom onset within the past 10 years) schizophrenia spectrum disorder (e.g. schizophrenia, schizoaffective disorder, or schizophreniform disorder) and will have working memory deficits (defined as below average performance on the letter n-back task of the PennCNB battery). As part of the study, they will receive oral administration of specified doses of CVL-562 (PF-06412562), in a random order with repeated functional magnetic resonance imaging and cognitive testing during those visits. The most common side effects of this compound are nausea and headache. This is a multi-site study that requires the efforts of 4 study sites in total (Columbia, State University of New York Stony Brook, UPenn, and Yale).

At time of results entry, secondary outcome results unavailable due to ongoing restrictions per the NIH

Conditions: Early Course Schizophrenia Spectrum Disorder
Being tested: CVL-562 (PF-06412562) 1 mg, CVL-562 (PF-06412562) 4 mg, CVL-562 (PF-06412562) 15 mg, CVL-562 (PF-06412562) 25 mg, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CVL-562 (PF-06412562) 1 mgDrug
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
CVL-562 (PF-06412562) 4 mgDrug
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
CVL-562 (PF-06412562) 15 mgDrug
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
CVL-562 (PF-06412562) 25 mgDrug
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
PlaceboOther
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).

Study groups in NCT04457310
Study group	Role	What they receive
CVL-562 (PF-06412562) 1 mg	Experimental	Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Receives: Drug: CVL-562 (PF-06412562) 1 mg
CVL-562 (PF-06412562) 4 mg	Experimental	Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Receives: Drug: CVL-562 (PF-06412562) 4 mg
CVL-562 (PF-06412562) 15 mg	Experimental	Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Receives: Drug: CVL-562 (PF-06412562) 15 mg
CVL-562 (PF-06412562) 25 mg	Experimental	Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Receives: Drug: CVL-562 (PF-06412562) 25 mg
Placebo	Placebo comparator	Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.
Measured: Up to two hours for each fMRI session
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.
Measured: Up to two hours for each fMRI session
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.
Measured: Up to two hours for each fMRI session
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.
Measured: Up to two hours for each fMRI session

Secondary outcomes (6)

Performance During Spatial Working Memory (sWM) Task
During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. Performance will be assessed with the average accuracy measured during this task for each task condition and each CVL-562 (PF-06412562) dose. Accuracy refers to the angular distance between a cued location and a participant's memory of the location. The range of accuracy is between 0-180 degrees. 0 degrees would indicate the best possible performance, and 180 degrees the worst performance. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Measured: Up to two hours for each fMRI session.
Association Between Neural Activity and Task Performance
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during fMRI, where subjects will participate in a spatial working memory (sWM) task. The sWM includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. The performance of sWM at each trial of each condition will be used as the predictor variable, and the BOLD signal at the corresponding trial and condition will be used as the outcome variable. A trial refers to a single probing and measurement of sWM, and is repeatedly presented to get a number of sWM measurements. The performance of sWM from each trial will be regressed with the BOLD signal from that trial, and we will report the resulting beta weights at each condition and dose. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Measured: Up to two hours for each fMRI session.
Functional Connectivity Across Brain Regions With the Fronto-parietal Network During sWM Task
Functional connectivity will be assessed during each fMRI session. Functional connectivity refers to the correlation between the time series of different brain regions collected during fMRI. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, the functional connectivity of the fronto-parietal network will be measured with the rest of the brain. The range of functional connectivity is between -4.95 and 4.95. -4.95 would indicate highly negative functional connectivity and 4.95 would indicate highly positive functional connectivity. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Measured: Up to two hours for each fMRI session.
Resting State Global Brain Functional Connectivity
BOLD signal will be collected during the resting state aspect of the fMRI session, using a data-driven global brain connectivity (GBC) metric. GBC examines connectivity from a given voxel (or area) to all other voxels (or areas) simultaneously by computing average connectivity strength. The range of GBC is between -4.95 and 4.95. -4.95 would indicate highly negative broad functional connectivity in synchrony with the rest of the brain and 4.95 would indicate highly positive broad functional connectivity in synchrony with the rest of the brain. GBC will be obtained at each PF-06412562 dose.
Measured: Up to two hours for each fMRI session.
Proportion of Participants With Change in Blood Oxygen Level Dependent (BOLD) Signal During Spatial Working Memory (sWM) Task.
The dose-response in BOLD signal will be examined for each individual participant to see how many participants exhibit a change in BOLD signal overall. For each individual, binary outcome will be calculated based on a Dose by Condition by Time within subject analysis of BOLD signal. We will report the proportion of participants that exhibits a dose response.
Measured: Up to two hours for each fMRI session.
Spatial Similarity of Resting State Global Brain Functional Connectivity With Transcriptomic Maps.
Transcriptomics maps will be derived from the Allen Human Brain Atlas (AHBA), which provides gene expression data mapped to the cortical surface. The spatial similarity of resting state global brain functional connectivity (GBC) and gene expression patterns for the D1/D5 receptors will be assessed for each CVL-562 (PF-06412562) dose. The spatial similarity refers to correlation between GBC maps and the cortical gene expression maps. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Measured: Up to two hours for each fMRI session.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Mar 202122 Mar 2024

First posted7 Jul 2020
Study start2 Mar 2021
Primary completion22 Mar 2024
Study completion22 Mar 2024

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 Early Course Schizophrenia Spectrum DisorderStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
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 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 112 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04457310
Sponsor's protocol ID: 2000027506
Other IDs: 1U01MH121766-01
Status last verified: Sep 2025
First submitted: 29 Jun 2020
Last updated: 15 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: De-identified data will be made publicly available through the NIMH Data Archive (NDAR) with data uploaded every 6 months.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Enhancing Prefrontal Oscillations and Working Memory in Early-course Schizophrenia
Schizophrenia
Recruiting
Restoring Spindle and Thalamocortical Efficiency in Early-Course Schizophrenia Patients Using Auditory Stimulation
Schizophrenia
RecruitingObservational study
Biomarkers/Biotypes, Course of Early Psychosis and Specialty Services
Schizophrenia Spectrum and Other Psychotic Disorders, Schizophrenia
Recruiting
Dimensional and Developmental Profiles of Psychosis in Children and Adolescents
Schizophrenia, Psychotic Disorders

All Early Course Schizophrenia Spectrum Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia
ClinicalTrials.gov ID: NCT04457310
Acronym / sponsor ID: 2000027506
Conditions: Early Course Schizophrenia Spectrum Disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 112 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: Columbia University, University of Pennsylvania, State University of New York Stony Brook, Cerevel Therapeutics, LLC, National Institute of Mental Health (NIMH)
Study start: 2 Mar 2021 (actual)
Primary completion: 22 Mar 2024 (actual)
Study completion: 22 Mar 2024 (actual)
First posted: 7 Jul 2020 (actual)
Results: Posted 15 Oct 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

At time of results entry, secondary outcome results unavailable due to ongoing restrictions per the NIH

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
CVL-562 (PF-06412562) 1 mg	Experimental	Drug: CVL-562 (PF-06412562) 1 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.
CVL-562 (PF-06412562) 4 mg	Experimental	Drug: CVL-562 (PF-06412562) 4 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.
CVL-562 (PF-06412562) 15 mg	Experimental	Drug: CVL-562 (PF-06412562) 15 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.
CVL-562 (PF-06412562) 25 mg	Experimental	Drug: CVL-562 (PF-06412562) 25 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.
Placebo	Placebo comparator	Other: PlaceboEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (12 listed)

Between the ages of 18 (including 18 years of age) and 45 (up to 45 years and 11 months) at the time of baseline study visit.
Able to provide informed consent (as established by consent interview), and voluntary, signed informed consent prior to the performance of any study-specific procedures
Willing and able to perform study-relevant clinical assessments and Magnetic Resonance Imaging (MRI) as assessed by research staff.
Meet Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder on the basis of the Structured Clinical Interview for DSM-5 (SCID-5).
Be within 10 years of the onset of psychosis based on clinical assessment at the time of Visit 1.

Key exclusion criteria (25 listed)

Any unstable medical, psychiatric, or neurological condition (including active or otherwise remarkable suicidal or homicidal ideation) that may necessitate urgent treatment. Active medical conditions that are minor or well controlled are not exclusionary if they do not affect risk to the patient, metabolism of study drug, or the study results (e.g. well-controlled type II diabetes or hypertension) as per the judgment of the investigator.
Be currently treated with any of the following: olanzapine, clozapine, ziprasidone or asenapine, in order to avoid prominent D1 receptor effects.
Any major neurological disease, brain injury, epilepsy, or history of severe head trauma, including concussion with loss of consciousness greater than or equal to > 15 minutes, or of psychosurgery.
History of significant cardiac disease (ex: ischemia, arrhythmia).
Any clinically significant abnormality on baseline medical screening tests (electrocardiogram (EKG), complete blood count with differential (CBC), complete metabolic profile (CMP).

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
CVL-562 (PF-06412562) 1 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).	Drug	CVL-562 (PF-06412562) 1 mg
CVL-562 (PF-06412562) 4 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).	Drug	CVL-562 (PF-06412562) 4 mg
CVL-562 (PF-06412562) 15 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).	Drug	CVL-562 (PF-06412562) 15 mg
CVL-562 (PF-06412562) 25 mgEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).	Drug	CVL-562 (PF-06412562) 25 mg
PlaceboEach subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).	Other	Placebo

Primary outcome

Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Time frame: Up to two hours for each fMRI session
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Time frame: Up to two hours for each fMRI session
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Time frame: Up to two hours for each fMRI session
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Time frame: Up to two hours for each fMRI session
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose.

6 secondary outcomes

Performance During Spatial Working Memory (sWM) Task
Time frame: Up to two hours for each fMRI session.
Association Between Neural Activity and Task Performance
Time frame: Up to two hours for each fMRI session.
Functional Connectivity Across Brain Regions With the Fronto-parietal Network During sWM Task
Time frame: Up to two hours for each fMRI session.
Resting State Global Brain Functional Connectivity
Time frame: Up to two hours for each fMRI session.
Proportion of Participants With Change in Blood Oxygen Level Dependent (BOLD) Signal During Spatial Working Memory (sWM) Task.
Time frame: Up to two hours for each fMRI session.
Spatial Similarity of Resting State Global Brain Functional Connectivity With Transcriptomic Maps.
Time frame: Up to two hours for each fMRI session.

Results and safety

Results posted to the registry on 15 Oct 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Study Participants	112	71

Primary outcome: Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2

Time frame: Up to two hours for each fMRI session. Mean (Standard Deviation). Unit: percentage signal change

Measure	CVL-562 (PF-06412562) 1 mg n = 50	CVL-562 (PF-06412562) 4 mg n = 50	CVL-562 (PF-06412562) 15 mg n = 50	CVL-562 (PF-06412562) 25 mg n = 50	Placebo n = 50
Second 0.8	-0.076 (0.165)	-0.090 (0.177)	-0.072 (0.180)	-0.136 (0.169)	-0.064 (0.161)
Second 1.6	-0.090 (0.217)	-0.097 (0.225)	-0.083 (0.223)	-0.167 (0.207)	-0.067 (0.212)
Second 2.4	-0.045 (0.235)	-0.042 (0.231)	-0.039 (0.235)	-0.135 (0.213)	-0.043 (0.232)
Second 3.2	0.024 (0.238)	0.028 (0.239)	0.031 (0.245)	-0.066 (0.228)	0.020 (0.223)
Second 4.0	0.092 (0.240)	0.094 (0.256)	0.104 (0.246)	-0.012 (0.235)	0.072 (0.237)
Second 4.8	0.119 (0.261)	0.137 (0.259)	0.143 (0.257)	0.027 (0.251)	0.110 (0.248)
Second 5.6	0.105 (0.271)	0.144 (0.263)	0.153 (0.265)	0.033 (0.246)	0.113 (0.246)
Second 6.4	0.078 (0.280)	0.118 (0.256)	0.127 (0.260)	0.006 (0.243)	0.100 (0.257)

Primary outcome: Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1

Time frame: Up to two hours for each fMRI session. Mean (Standard Deviation). Unit: percentage signal change

Measure	CVL-562 (PF-06412562) 1 mg n = 50	CVL-562 (PF-06412562) 4 mg n = 50	CVL-562 (PF-06412562) 15 mg n = 50	CVL-562 (PF-06412562) 25 mg n = 50	Placebo n = 50
Second 0.8	-0.070 (0.155)	-0.040 (0.148)	-0.060 (0.164)	-0.065 (0.151)	-0.081 (0.152)
Second 1.6	-0.086 (0.200)	-0.036 (0.197)	-0.076 (0.218)	-0.079 (0.184)	-0.093 (0.187)
Second 2.4	-0.042 (0.200)	0.013 (0.214)	-0.039 (0.216)	-0.045 (0.197)	-0.053 (0.198)
Second 3.2	0.025 (0.228)	0.074 (0.225)	0.025 (0.220)	0.010 (0.193)	0.012 (0.204)
Second 4.0	0.071 (0.243)	0.131 (0.223)	0.081 (0.245)	0.060 (0.207)	0.068 (0.216)
Second 4.8	0.089 (0.243)	0.151 (0.223)	0.109 (0.266)	0.091 (0.224)	0.098 (0.224)
Second 5.6	0.087 (0.251)	0.145 (0.219)	0.096 (0.287)	0.089 (0.228)	0.090 (0.228)
Second 6.4	0.054 (0.255)	0.126 (0.212)	0.067 (0.280)	0.067 (0.236)	0.059 (0.237)

Primary outcome: Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3

Time frame: Up to two hours for each fMRI session. Mean (Standard Deviation). Unit: percentage signal change

Measure	CVL-562 (PF-06412562) 1 mg n = 50	CVL-562 (PF-06412562) 4 mg n = 50	CVL-562 (PF-06412562) 15 mg n = 50	CVL-562 (PF-06412562) 25 mg n = 50	Placebo n = 50
Second 0.8	-0.108 (0.134)	-0.100 (0.112)	-0.122 (0.130)	-0.072 (0.119)	-0.122 (0.095)
Second 1.6	-0.108 (0.150)	-0.116 (0.118)	-0.129 (0.137)	-0.077 (0.127)	-0.128 (0.105)
Second 2.4	-0.063 (0.153)	-0.072 (0.122)	-0.073 (0.137)	-0.043 (0.127)	-0.078 (0.099)
Second 3.2	0.017 (0.147)	-0.004 (0.122)	-0.003 (0.131)	0.025 (0.121)	0.004 (0.111)
Second 4.0	0.074 (0.151)	0.044 (0.134)	0.053 (0.127)	0.069 (0.114)	0.054 (0.116)
Second 4.8	0.108 (0.145)	0.067 (0.134)	0.087 (0.129)	0.102 (0.105)	0.074 (0.116)
Second 5.6	0.100 (0.162)	0.072 (0.120)	0.095 (0.128)	0.095 (0.110)	0.070 (0.115)
Second 6.4	0.086 (0.167)	0.051 (0.122)	0.079 (0.126)	0.058 (0.109)	0.046 (0.110)

Primary outcome: Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4

Time frame: Up to two hours for each fMRI session. Mean (Standard Deviation). Unit: percentage signal change

Measure	CVL-562 (PF-06412562) 1 mg n = 50	CVL-562 (PF-06412562) 4 mg n = 50	CVL-562 (PF-06412562) 15 mg n = 50	CVL-562 (PF-06412562) 25 mg n = 50	Placebo n = 50
Second 0.8	-0.124 (0.119)	-0.120 (0.134)	-0.133 (0.118)	-0.137 (0.109)	-0.110 (0.124)
Second 1.6	-0.120 (0.133)	-0.123 (0.144)	-0.138 (0.132)	-0.146 (0.113)	-0.109 (0.137)
Second 2.4	-0.079 (0.139)	-0.090 (0.134)	-0.090 (0.137)	-0.109 (0.113)	-0.066 (0.140)
Second 3.2	-0.021 (0.139)	-0.023 (0.137)	-0.022 (0.124)	-0.040 (0.111)	-0.013 (0.133)
Second 4.0	0.043 (0.142)	0.034 (0.138)	0.044 (0.124)	0.011 (0.119)	0.046 (0.131)
Second 4.8	0.078 (0.143)	0.060 (0.136)	0.079 (0.118)	0.039 (0.138)	0.079 (0.134)
Second 5.6	0.085 (0.144)	0.050 (0.135)	0.093 (0.118)	0.049 (0.146)	0.062 (0.118)
Second 6.4	0.068 (0.141)	0.028 (0.140)	0.078 (0.131)	0.039 (0.139)	0.044 (0.109)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 21 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CVL-562 (PF-06412562) 1mg	0 of 84 (0%)	20 of 84 (23.8%)	0 of 84
CVL-562 (PF-06412562) 4mg	0 of 84 (0%)	21 of 84 (25%)	0 of 84
CVL-562 (PF-06412562) 15mg	1 of 84 (1.2%)	29 of 84 (34.5%)	0 of 84
CVL-562 (PF-06412562) 25mg	0 of 84 (0%)	35 of 84 (41.7%)	0 of 84
Placebo	0 of 84 (0%)	24 of 84 (28.6%)	0 of 84
Adverse Event Prior to Starting Intervention	1 of 84 (1.2%)	0 of 84 (0%)	0 of 84

Limitations and caveats (from the sponsor): Secondary outcome data is unavailable at this time due to the ongoing restrictions at the Columbia/New York State Psychiatric Institute (NYSPI) site, preventing data access and sharing described in the approved GCE.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. De-identified data will be made publicly available through the NIMH Data Archive (NDAR) with data uploaded every 6 months.

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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.

John Krystal, MD principal investigator

Yale University

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 12 inclusion and 25 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 15 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 15 Oct 2025). 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?

Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 (time frame: Up to two hours for each fMRI session). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04457310.

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 15 Oct 2025.