CVL-354 for Healthy Subjects

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Cerevel Therapeutics, LLC

Must not be taking: Prescription medications

Disqualifiers: Cardiovascular, Pulmonary, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CVL-354 in healthy participants to observe how different doses affect the body. The trial consists of two parts: one tests single doses, and the other tests multiple doses over time. Participants will receive either the treatment or a placebo, a look-alike substance with no active ingredients, to compare results. The trial seeks healthy volunteers aged 18 to 55 with no serious health issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires participants to avoid certain medications, including prescription and over-the-counter drugs, herbal medications, vitamins, and supplements. You may need to stop taking your current medications if they are considered prohibited for the trial.

Is there any evidence suggesting that CVL-354 is likely to be safe for humans?

Research has shown that CVL-354 blocks certain brain receptors linked to mood and behavior. In animal studies, this drug reduced signs of opioid withdrawal, suggesting a calming effect without major harm.

The current trial is in its early phase, focusing on testing the drug's safety in humans. This phase typically involves small groups to observe how the body reacts to the drug. While specific data on human response to CVL-354 is not yet available, its testing in humans indicates it passed initial safety checks in earlier animal studies.

If the FDA had already approved CVL-354 for another condition, it might provide more confidence in its safety. However, that is not the case here, so the main safety evidence comes from animal studies and this early trial phase. Consulting a healthcare professional before joining any trial is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CVL-354 because it offers a novel approach to treating conditions that involve the brain's receptors. Unlike the standard options that generally target common neurotransmitter pathways, CVL-354 specifically locks onto the kappa opioid receptors, which might lead to fewer side effects and better effectiveness in managing mood and anxiety disorders. This targeted action is particularly promising for those who haven’t found relief with existing treatments, and it may provide a faster onset of benefits.

What evidence suggests that this trial's treatments could be effective?

Research shows that CVL-354 is a promising new treatment under study for its effects on certain brain receptors that help control mood and stress. In this trial, participants will receive different dosages of CVL-354 or a placebo to evaluate its effects. Animal studies have shown that CVL-354 can reduce physical signs of withdrawal from opioids, suggesting it could help manage symptoms related to opioid use. Although limited data from human studies exist, early results support its expected effects in the brain, offering hope for its effectiveness in treating related conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Matthew Leoni, MD, MBA

Principal Investigator

Cerevel Therapeutics, LLC

Are You a Good Fit for This Trial?

Inclusion Criteria

A man who is participating in the trial and who has a pregnant or partner who is able to have children must agree to use contraception during the trial and for 14 days after the last dose of study drug.

Capable of giving signed informed consent

The person's body mass index is between 18.5 and 30.0 kg/m2, and their total body weight is over 50 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive single ascending doses of CVL-354 in a 4-way crossover design with washout periods

Up to 72 days

Treatment Part B

Participants receive multiple ascending doses of CVL-354 or placebo once daily for 14 days

Up to 31 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 72 days

What Are the Treatments Tested in This Trial?

Interventions

• CVL-354
• Placebo

How Is the Trial Designed?

Group I: Part B: Cohort 5: CVL-354 85 mg Experimental Treatment 2 Interventions

Participants received oral dose of CVL-354 85 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 5.

Group II: Part B: Cohort 4: CVL-354 80 mg Experimental Treatment 2 Interventions

Participants received oral dose of CVL-354 80 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 4.

Group III: Part B: Cohort 3: CVL-354 50 mg Experimental Treatment 2 Interventions

Participants received oral dose of CVL-354 50 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 3.

Group IV: Part B: Cohort 2: CVL-354 25 mg Experimental Treatment 2 Interventions

Participants received oral dose of CVL-354 25 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 2.

Group V: Part B: Cohort 1: CVL-354 10 mg Experimental Treatment 2 Interventions

Participants received oral dose of CVL-354 10 mg or Placebo, once daily (QD) from Day 1 up to Day 14 in Cohort 1.

Group VI: Part A: Cohort 3: Sequence 2: Fasted/Fed Sequence Experimental Treatment 1 Intervention

Participants first received a single oral dose of CVL-354 50 mg, under fasted state on Day 1 of Period 1 followed by a single oral dose of CVL-354 50 mg under fed state on Day 1 of Period 2, with a washout period of 2 days between both periods

Group VII: Part A: Cohort 3: Sequence 1: Fed/Fasted Sequence Experimental Treatment 1 Intervention

Participants first received a single oral dose of CVL-354 50 mg, under fed state on Day 1 of Period 1 followed by a single oral dose of CVL-354 50 mg under fasted state on Day 1 of Period 2, with a washout period of 2 days between both periods.

Group VIII: Part A: Cohort 2: Sequence 4 Experimental Treatment 2 Interventions

Participants were randomized to sequence 4 to receive CVL-354 45 mg on Day 1 of Period 1 followed by CVL-354 90 mg on Day 1 of Period 2, followed by CVL-354 150 mg on Day 1 of Period 3 \& placebo on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Group IX: Part A: Cohort 2: Sequence 3 Experimental Treatment 2 Interventions

Participants were randomized to sequence 3 to receive CVL-354 45 mg on Day 1 of Period 1 followed by CVL-354 on 90 mg Day 1 of Period 2, followed by placebo on Day 1 of Period 3 \& followed by CVL-354 200 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Group X: Part A: Cohort 2: Sequence 2 Experimental Treatment 2 Interventions

Participants were randomized to sequence 2 to receive CVL-354 45 mg on Day 1 of Period 1 followed by placebo on Day 1 of Period 2, followed by CVL-354 150 mg on Day 1 of Period 3 \& followed by CVL-354 200 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Group XI: Part A: Cohort 2: Sequence 1 Experimental Treatment 2 Interventions

Participants were randomized to sequence 1 to receive placebo on Day 1 of Period 1 followed by CVL-354 90 mg on Day 1 of Period 2, followed by CVL-354 150 mg on Day 1 of Period 3 \& followed by CVL-354 200 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Group XII: Part A: Cohort 1: Sequence 4 Experimental Treatment 2 Interventions

Participants were randomized to sequence 4 to receive CVL-354 0.5 mg on Day 1 of Period 1 followed by CVL-354 1.5 mg on Day 1 of Period 2, followed by CVL-354 5 mg on Day 1 of Period 3 \& followed by placebo on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Group XIII: Part A: Cohort 1: Sequence 3 Experimental Treatment 2 Interventions

Participants were randomized to sequence 3 to receive CVL-354 0.5 mg on Day 1 of Period 1 followed by CVL-354 1.5 mg on Day 1 of Period 2, followed by placebo on Day 1 of Period 3 \& followed by CVL-354 15 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Group XIV: Part A: Cohort 1: Sequence 2 Experimental Treatment 2 Interventions

Participants were randomized to sequence 2 to receive CVL-354 0.5 mg on Day 1 of Period 1 followed by placebo on Day 1 of Period 2, followed by CVL-354 5 mg on Day 1 of Period 3 \& followed by CVL-354 15 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Group XV: Part A: Cohort 1: Sequence 1 Experimental Treatment 2 Interventions

Participants were randomized to sequence 1 to receive placebo on Day 1 of Period 1 followed by CVL-354 1.5 milligrams (mg) on Day 1 of Period 2, followed by CVL-354 5 mg on Day 1 of Period 3 \& followed by CVL-354 15 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.

Who Is Running the Clinical Trial?

Cerevel Therapeutics, LLC

Lead Sponsor

Trials

37

Recruited

5,500+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1.

reporter.nih.gov

reporter.nih.gov/project-details/10823715

CVL-354, a kappa opioid receptor antagonist for treatment ...

A short-acting, selective KOR antagonist. This compound, CVL-354, attenuated the physical signs of withdrawal in an acute opioid withdrawal model in rodents.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05138653

A Single and Multiple Ascending Dose Trial of CVL-354 in ...

Study Overview​​ This is a 2-part, double-blind, randomized, placebo-controlled, first-in-human trial evaluating a single ascending dose (4-way crossover, Part A ...

3.

abbvieclinicaltrials.com

abbvieclinicaltrials.com/study/?id=CVL-354-1002

CVL-354-1002

The primary purpose of this study is to assess the target occupancy at kappa and mu opioid receptors in the brain after single oral doses of CVL-354 in healthy ...

4.

synapse.patsnap.com

synapse.patsnap.com/drug/fc314c1614d64e1283e1ae43502c5057

CVL 354 - Drug Targets, Indications, Patents

A Phase 2, Multicenter, 6-Week, Double Blind, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Icalcaprant in Subjects With Bipolar Depression.

5.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/53/NCT05138653/Prot_000.pdf

A Phase 1, Double-blind (Investigator and Participant), First ...

The aim of this 2-part, first-in-human trial is to investigate the safety, tolerability, and pharmacokinetics (PK) of CVL-354, following single ...

6.

adisinsight.springer.com

adisinsight.springer.com/drugs/800057691

Icalcaprant - Cerevel Therapeutics - AdisInsight - Springer

Icalcaprant (formerly known as CVL 354) is a kappa opiate receptor antagonist (KORA), being developed by Cerevel Therapeutics (a subsidiary of AbbVie), ...

7.

clinicalresearch.com

clinicalresearch.com/en/find-trials/Study/NCT05547542

NCT05547542

The primary purpose of this study is to assess the target occupancy at kappa and mu opioid receptors in the brain after single oral doses of CVL-354 in healthy ...