Dopamine Receptor Agonist for Schizophrenia

No longer recruiting at 3 trial locations

Overseen By John Krystal, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Olanzapine, Clozapine, Ziprasidone, Asenapine

Disqualifiers: Unstable conditions, Neurological disease, Cardiac disease, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, CVL-562 (a dopamine receptor agonist), to determine if it can improve memory and cognitive function in people with early-stage schizophrenia. Researchers aim to address cognitive issues that complicate daily life for those with the condition. Participants will receive varying doses of the medication or a placebo to better understand its effects. This trial may suit individuals diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder who are within 10 years of their first psychotic episode. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable psychotropic medication regimen for at least 3 weeks before starting and during the study. However, you cannot be on certain medications like olanzapine, clozapine, ziprasidone, or asenapine, and must avoid certain other medications or substances 10 days before and during the study.

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

Research has shown that CVL-562 (also known as PF-06412562) is generally safe and well-tolerated in people with schizophrenia. In earlier studies, participants reported no major side effects from this treatment. The drug targets dopamine receptors, which play a role in brain functions related to schizophrenia. Although these results are encouraging, this study remains in an early stage, and further research is necessary to confirm its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for schizophrenia?

Researchers are excited about CVL-562 for schizophrenia because it targets dopamine receptors differently than current standard treatments like antipsychotics, which often come with significant side effects. Unlike traditional medications that block dopamine receptors, CVL-562 is a dopamine receptor agonist, meaning it activates these receptors in a more controlled way. This unique mechanism could offer effective symptom management while potentially reducing the risk of side effects like weight gain and motor issues commonly associated with current therapies.

What evidence suggests that CVL-562 could be an effective treatment for schizophrenia?

Studies have shown that CVL-562 (PF-06412562) targets specific parts of the brain called dopamine D1 receptors. These receptors are linked to memory and thinking skills, which can be affected in people with schizophrenia. Research suggests that activating D1 receptors can improve thinking skills in animal studies simulating schizophrenia. However, studies in humans have not yet clearly demonstrated its effectiveness in treating schizophrenia. While this treatment shows promise, more research is needed to confirm its benefits for people with schizophrenia. Participants in this trial will receive different doses of CVL-562 (PF-06412562) or a placebo to evaluate its effectiveness and safety. ^{1 3 6 7 8}

Who Is on the Research Team?

John Krystal, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-45 with early episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. They must be fluent in English, not pregnant or planning to become so during the study, and on stable psychiatric medication for at least two months. Participants should have no significant medical conditions that could interfere with the study.

Inclusion Criteria

Demonstrate a premorbid IQ of ≥80 based on the Penn Reading Assessment (PRA)

I can follow simple instructions and move as needed for a memory task.

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)

Exclusion Criteria

I am allergic or react badly to certain medications.

I have a history of serious heart problems.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CVL-562 (PF-06412562) at different doses or placebo over 5 test visits, with repeated fMRI and cognitive testing

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CVL-562 (PF-06412562) 15 mg
• CVL-562 (PF-06412562) 1 mg
• CVL-562 (PF-06412562) 25 mg
• CVL-562 (PF-06412562) 4 mg
• Placebo

Trial Overview

The trial is testing CVL-562 (PF-06412562), a dopamine receptor partial agonist at different doses (1 mg, 4 mg, 15 mg, and 25 mg) against a placebo. It aims to see if this drug can improve working memory by engaging certain brain receptors using neuroimaging as a measure of effectiveness.

How Is the Trial Designed?

Group I: CVL-562 (PF-06412562) 4 mg Experimental Treatment 1 Intervention

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.

Group II: CVL-562 (PF-06412562) 25 mg Experimental Treatment 1 Intervention

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.

Group III: CVL-562 (PF-06412562) 15 mg Experimental Treatment 1 Intervention

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.

Group IV: CVL-562 (PF-06412562) 1 mg Experimental Treatment 1 Intervention

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.

Group V: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

State University of New York Stony Brook

Collaborator

Trials

1

Recruited

110+

Cerevel Therapeutics, LLC

Industry Sponsor

Trials

37

Recruited

5,500+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31264510/

A Novel Approach to Evaluate the Pharmacodynamics of ...

Conclusions: Adjunctive treatment with PF-06412562 was safe and well tolerated in patients with schizophrenia. PF-06412562 failed to show ...

2.

withpower.com

withpower.com/trial/phase-2-schizophrenia-2-2021-f3881

Dopamine Receptor Agonist for Schizophrenia

CVL-562 (PF-06412562) is unique because it acts as a dopamine receptor agonist, specifically targeting D2 receptors, which are often elevated in schizophrenia.

3.

medrxiv.org

medrxiv.org/content/10.1101/2025.04.18.25326082v1.full-text

Rationale and Study Design of a Brain-Based Clinical Trial

... CVL-562 (13). Unfortunately, the initial Phase IB study of CVL-562 in schizophrenia was negative and did not provide a clear guidance for ...

4.

academic.oup.com

academic.oup.com/ijnp/article/23/5/287/5735643

A Neurofunctional Domains Approach to Evaluate D1/D5 ...

We note that multiple studies in nonhuman primates have demonstrated single-dose pro-cognitive effects of D1R agonists in schizophrenia-related models with very ...

5.

clinicaltrials.gov

clinicaltrials.gov/show/NCT02418819

A Study To Examine Safety, Pharmacokinetics, And ...

Evidence of stable schizophrenia symptomatology for at least 3 months (no hospitalizations for schizophrenia, no increase in level of psychiatric care due to ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02418819

A Study To Examine Safety, Pharmacokinetics, And ...

A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia. ClinicalTrials.gov ID NCT02418819. Sponsor ...

7.

cdek.pharmacy.purdue.edu

cdek.pharmacy.purdue.edu/trial/NCT04457310/

Trial | NCT04457310

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 ...

8.

ctv.veeva.com

ctv.veeva.com/study/a-translational-and-neurocomputational-evaluation-of-a-dopamine-receptor-1-partial-agonist-for-schiz

A Translational and Neurocomputational Evaluation of a ...

This study will test whether CVL-562 (PF-06412562), a dopamine 1 ... schizophrenia, a key unaddressed clinical and public health concern.