Adjunctive Aticaprant and Antidepressant Therapy for Relapse Prevention in Major Depressive Disorder with Moderate-to-Severe Anhedonia: A Randomized, Double-Blind Study

The primary objective of this study is to evaluate the **efficacy** of aticaprant 10 mg administered once daily, in comparison to a placebo, as an adjunctive therapy to an antidepressant (SSRI/SNRI) in delaying the relapse of depressive symptoms in adult participants with **Major Depressive Disorder (MDD)** with moderate-to-severe **anhedonia** who have achieved a stable response. This is clinically relevant as it addresses the challenge of relapse prevention in MDD, a condition characterized by persistent depressive symptoms that significantly impair daily functioning and quality of life. The study aims to provide insights into the potential benefits of aticaprant in maintaining remission and preventing relapse, which is crucial for long-term management of MDD.

The clinical trial involves a total of **321 participants** diagnosed with **Major Depressive Disorder (MDD)** with moderate-to-severe anhedonia. The study population comprises adults aged 18 to 64 years, inclusive, and includes both male and female subjects. Participants were selected based on their medical stability, as determined by physical examinations, medical history, vital signs, and laboratory tests. The trial specifically targets individuals who meet the DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features, and who exhibit symptoms of anhedonia. The participants are required to be medically stable, with any laboratory abnormalities deemed not clinically significant by the investigator. The trial does not specify particular lifestyle considerations such as diet or physical activity. The study includes a vulnerable population, ensuring a comprehensive assessment of the efficacy of aticaprant as an adjunctive therapy to an antidepressant in delaying relapse of depressive symptoms.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy of **aticaprant** as an adjunctive therapy to an antidepressant in preventing relapse in adults with **Major Depressive Disorder (MDD)** with moderate-to-severe anhedonia. The trial will involve the administration of aticaprant 10 mg once daily compared to a matching placebo, both in conjunction with a standard antidepressant regimen. The study is expected to commence recruitment on November 30, 2024, and conclude by May 13, 2027, with a maximum treatment period of 43 days for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, medical stability, and diagnostic confirmation of MDD with anhedonia. Following successful screening, participants will be randomized into the double-blind treatment phase. During this phase, regular follow-up visits will be conducted to monitor the participants' response to treatment and any adverse events. The primary endpoint is the time from randomization to the first documentation of a relapse event. The study will conclude with an end-of-study visit to evaluate the overall outcomes and gather final data.

Participant involvement is expected to last up to 43 days, with conditions for early termination including significant adverse events, withdrawal of consent, or any other medical reasons deemed necessary by the investigator. The trial aims to provide robust data on the efficacy of aticaprant in delaying depressive relapse, contributing valuable insights into the management of MDD with anhedonia.

The clinical trial involves the administration of **JNJ-67953964**, an experimental medication containing the active substance **aticaprant**. This medication is formulated as a tablet and is intended for **oral use**. Participants will receive a dosage of 10 mg once daily. The maximum daily dose is 10 mg, with a total maximum dose of 430 mg over a treatment period of 43 days. The medication is developed by Janssen-Cilag International N.V. and is classified as an antidepressant and opioid antagonist. The primary objective of the trial is to evaluate the efficacy of aticaprant as an adjunctive therapy to an antidepressant (SSRI/SNRI) in delaying relapse of depressive symptoms in adults with Major Depressive Disorder (MDD) who have achieved a stable response.

In addition to the experimental medication, a **matching placebo tablet** is used as a comparator treatment in this double-blind, placebo-controlled study. The placebo is designed to mimic the appearance and administration route of the active medication, ensuring that neither the participants nor the investigators can distinguish between the active treatment and the placebo. The placebo is administered once daily, following the same schedule as the active medication, to maintain the study's blinding integrity.

The efficacy of the investigational product, **aticaprant**, will be assessed in a randomized, double-blind, multicenter, placebo-controlled clinical trial. The primary objective is to evaluate the efficacy of aticaprant 10 mg once daily, compared with placebo, as an adjunctive therapy to an antidepressant (SSRI/SNRI) in delaying the relapse of depressive symptoms in adult participants with Major Depressive Disorder (MDD) who have achieved a stable response. The primary endpoint for efficacy assessment is the time from randomization into the double-blind treatment maintenance phase to the first documentation of a relapse event. This endpoint will be measured and documented throughout the trial to determine the effectiveness of the treatment in preventing relapse.