A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants with Major Depressive Disorder (MDD) with Moderate-to-Severe Anhedonia and Inadequate Response to Current Antidepressant Therapy and an Open- labeled Long-term Extension Treatment with Aticaprant

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen Cilag International

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

14 Nov 2024 → 24 Apr 2025

Decision date (initial)

2024-10-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Pharmacodynamic, Efficacy

To evaluate the efficacy of aticaprant 10 mg compared with placebo as adjunctive therapy to an antidepressant in improving depressive symptoms in adult participants with MDD with moderate-to-severe anhedonia who have had an inadequate response to current antidepressant therapy with an SSRI or SNRI

Conditions and MedDRA coding

Major Depressive Disorder (MDD) with Moderate-to-severe Anhedonia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adults aged 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 64 years, inclusive.
2. Meet DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features, based upon clinical assessment and confirmed by the SCID-CT
3. Moderate to severe depressive episode: MADRS ≥25 at Screening and Baseline Stable symptom severity - no clinically significant improvement (ie, >25%) between 2 the site-rater assessments
4. Have symptoms of anhedonia based on clinical assessment and confirmed by presence of anhedonia (positive response to MDE module symptom Item 2) on the SCID-CT at screening and have a SHAPS total score.
5. Have had an inadequate response to at least 1 and up to 5 (inclusive) oral antidepressant treatments, administered at an adequate dose (at or above the minimum therapeutic dose per MGH ATRQ) and duration (at least 6 weeks) in the current episode of depression, including current SSRI/SNRI treatment
6. Be medically stable based on clinical assessment , vital signs and ECG and laboratory assessments

Exclusion criteria 4

1. Has had no response (treatment failure) to 2 or more consecutive antidepressant treatments administered at an adequate dose (at or above the minimum therapeutic dose) and duration (at least 6 weeks) in the current episode of depression including the current SSRI/SNRI (ie, the one to be continued in the treatment phases) assessed using the MGH-ATRQ.
2. Has one or more of the following diagnoses: A current or prior (lifetime) DSM-5 diagnosis of: a psychotic disorder or MDD with psychotic features; bipolar or related disorders; intellectual disability; autism spectrum disorder; personality disorders (borderline, antisocial, histrionic, narcissistic); somatoform disorders A primary DSM-5 diagnosis (which has been the primary focus of psychiatric treatment within the past 2 years) of: panic disorder; generalized anxiety disorder; social anxiety disorder; specific phobia (allowed as secondary diagnosis); A current (in the past year) DSM-5 diagnosis of:obsessive-compulsive disorder (OCD),post-traumatic stress disorder (PTSD),anorexia nervosa, bulimia nervosa (allowed if stable for 1 year)
3. Has current suicidal risk, per investigator’s clinical judgment or based on the C-SSRS.
4. Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen Cilag International

Sponsor organisation

Janssen Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Third parties 6

Locations

8 EU/EEA countries · 56 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 102 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications