Aticaprant + Antidepressant for Depression

(VENTURA-5 Trial)

No longer recruiting at 119 trial locations

Overseen By Study Contact

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: SSRI, SNRI

Disqualifiers: Substance use disorder, Suicidal ideation, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a new drug, aticaprant, works when combined with common antidepressants like SSRIs or SNRIs. The goal is to determine if aticaprant can prevent the return of depression symptoms, particularly in individuals who have lost interest or pleasure in activities despite some improvement with current treatment. Participants should have major depressive disorder with a stable response to aticaprant and experience anhedonia (lack of interest or pleasure). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for depression.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it involves taking aticaprant in addition to your current antidepressant (SSRI or SNRI). It seems you will continue your existing antidepressant therapy while participating.

Is there any evidence suggesting that aticaprant is likely to be safe for humans?

Research shows that aticaprant is generally well-tolerated. Studies have found it has few side effects, with mild headaches and diarrhea being the most common. Specifically, 11.8% of people taking aticaprant reported headaches, compared to 7.1% of those on a placebo. Overall, the safety results are encouraging, particularly when aticaprant is used with antidepressants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Aticaprant is unique because it targets a specific brain receptor known as the kappa opioid receptor, which plays a role in mood regulation. Unlike traditional antidepressants that primarily increase serotonin or norepinephrine levels, aticaprant offers a different mechanism of action by potentially reducing stress-related symptoms of depression. Researchers are excited about its potential to provide relief for patients who may not respond well to current antidepressant medications, offering a new avenue for treatment that could complement existing therapies.

What evidence suggests that aticaprant might be an effective treatment for depression?

Research has shown that aticaprant, when combined with common antidepressants like SSRIs or SNRIs, can significantly reduce depression symptoms. Studies found that people with major depressive disorder who didn't fully improve with standard antidepressants experienced better outcomes when aticaprant was added to their treatment. This drug targets the kappa opioid receptor, which is believed to influence mood. Participants in earlier studies reported feeling less depressed and experiencing more pleasure. In this trial, participants will receive either aticaprant or a placebo alongside their antidepressant treatment. Overall, evidence suggests that aticaprant could be a valuable addition for those who don't respond well to traditional antidepressants. ^{1 3 4 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with Major Depressive Disorder who still feel a loss of interest and pleasure despite being on antidepressants. They should have had some improvement with aticaprant added to their treatment. People can't join if they have other mental health conditions, are pregnant or breastfeeding, or are at risk of suicide.

Inclusion Criteria

I have been diagnosed with depression without experiencing psychosis.

My health is stable as confirmed by recent medical exams.

My recent lab tests show that my health is stable.

Exclusion Criteria

History of moderate-to-severe substance use disorder within 6 months before screening

I have not followed my antidepressant treatment as prescribed.

My depression hasn't improved after trying 2 different antidepressants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

Participants receive open-label treatment with adjunctive aticaprant to achieve a stable response

16 weeks

Double-blind Treatment Maintenance

Participants are randomized to receive either aticaprant or placebo in addition to their antidepressant therapy to prevent relapse

Up to 2 years 2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aticaprant

Trial Overview The study tests whether adding Aticaprant to regular antidepressant therapy (SSRI or SNRI) prevents the return of depression symptoms better than a placebo in those who've seen initial improvements but still struggle with anhedonia.

How Is the Trial Designed?

Group I: Aticaprant Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

A large cohort study found that patients with gastric cancer who used antidepressants (ATDs) after surgery had improved overall survival (OS), with a clear dose-dependent relationship indicating that higher ATD use correlated with longer survival times.

The study analyzed data from patients diagnosed between 1999 and 2008, revealing that those taking higher cumulative doses of ATDs had significantly lower hazard ratios for mortality, suggesting that ATDs may have a beneficial effect on survival outcomes in gastric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressants use is associated with overall survival improvement of patients with gastric cancer after surgery and adjuvant chemotherapy in Taiwan: A large population-based cohort study. Shih, WT., Yang, PR., Chen, KJ., et al.[2023]

In a study of 12 patients with resectable advanced gastric cancer, the combination of S-1 and CDDP as neoadjuvant chemotherapy showed a high preoperative response rate of 75%, indicating its potential effectiveness.

The treatment was well-tolerated with no severe adverse reactions reported, but further evaluation in clinical trials is necessary to determine the long-term survival benefits of this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[S-1/CDDP combined neoadjuvant chemotherapy and surgical resection for advanced gastric cancer. Analysis of 12 patients with lymph node metastasis in Saitama Red Cross Hospital]. Nakamura, Y., Nakagawa, K., Fujita, M., et al.[2013]

In three cases of recurrent gastric cancer where S-1 chemotherapy was ineffective, the combination of irinotecan (CPT-11) and cisplatin (CDDP) led to complete responses (CR) in all patients, demonstrating its efficacy as a second-line treatment.

The treatment regimen of CPT-11 and CDDP was administered every two weeks, with significant tumor reductions observed after varying numbers of courses, indicating a potential alternative for patients who do not respond to S-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Three successful cases with CPT-11 + CDDP chemotherapy where S-1 failed to respond to recurrent gastric cancer]. Handa, R., Iijima, S., Doi, T., et al.[2018]

In a phase I/II pilot study involving 30 patients with refractory or recurrent non-small cell lung cancer (NSCLC), the combination of weekly paclitaxel and carboplatin demonstrated a promising response rate of 50% and a median survival time of 12 months.

The treatment was well-tolerated with mild toxicity, indicating that it could be a viable option for further investigation in phase III trials against other standard treatments like docetaxel or pemetrexed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of paclitaxel + carboplatin for refractory or recurrent non-small cell lung cancer. Gemma, A., Seike, M., Kosaihira, S., et al.[2015]

In a study of 321 patients with advanced stomach cancer, the intensive therapy group experienced more adverse reactions, including significant decreases in blood cell counts and higher rates of nausea and vomiting compared to the standard therapy group.

Despite the increased side effects in the intensive therapy group, there was no significant difference in 3-year survival or disease-free survival rates between the intensive and standard therapy groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Interim report of JFMTC study no. 20 on the effectiveness of high dose CDDP plus 5-FU regimen as an adjuvant therapy for far-advanced cancer of the stomach]. Toge, T., Fujita, M., Hirata, K., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38649428/

Efficacy and safety of aticaprant, a kappa receptor ... In this study of participants with MDD and inadequate response to SSRI/SNRI, adjunctive treatment with aticaprant significantly reduced depressive symptoms ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38969753/

Aticaprant, a kappa opioid receptor antagonist, and the ... Tolerability and safety were reassuring. These promising results of the co-administration of aticaprant to an SSRI/SNRI in depressed patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05455684

A Study of Aticaprant as Adjunctive Therapy in Adult ... The purpose of this study is to evaluate the efficacy of aticaprant compared with placebo as adjunctive therapy to an antidepressant in improving depressive ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724010863

Preclinical and clinical efficacy of kappa opioid receptor ... Aticaprant and navacaprant reduced depressive symptoms in persons with MDD. •. Treatment-emergent adverse events were mild in severity and ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/14728214.2024.2345645

Full article: Aticaprant: (a κ-opioid receptor antagonist) for ... The observed impact of Aticaprant on brain areas associated with pleasure and the reduction in clinical anhedonia, assessed by the Snaith-Hamilton Pleasure ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06514742

NCT06514742 | A Study of Aticaprant 10 mg as Adjunctive ... The purpose of this study is to evaluate how well aticaprant works as compared with placebo when given along with an antidepressant therapy in improving the ...