Comparison of esketamine with an antidepressant versus aripiprazole with an antidepressant, in the refractory major depression disorder in elderly patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

20 Feb 2026 → ongoing

Decision date (initial)

2024-11-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ISCIII institute public funding EXP ICI23_00029

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of esketamine nasal spray at flexible doses compared to aripiprazole at 8 weeks, both in combination with a continued antidepressant, in elderly participants (>60 years), who suffer from refractory major depression disorder (RMDD) with one episode current moderate to severe depressive disorder.

Secondary objectives 11

1. To evaluate the efficacy of esketamine nasal spray at flexible doses compared to aripiprazole at the end of the observation period at week 32, both in combination with an ongoing antidepressant, in elderly participants (>60 years) with a current moderate to severe depressive episode
2. To evaluate the safety of esketamine nasal spray compared to aripiprazole, both in combination with an antidepressant in continuous therapy at week 8
3. To evaluate the safety of esketamine nasal spray compared to aripiprazole, both in combination with an antidepressant in continuous therapy at week 32 in those patients free of relapse at week 8
4. To compare the relapses of the disease in the experimental group and in the control group at week 24 and week 32 from the start of treatment
5. To compare the evolution of the perceived quality of life in both groups of treatment
6. To perform whole genome sequencing analysis in patients who suffer refractory major depression disorder (RMDD)
7. To perform transcriptome sequencing (RNA-seq) at baseline and after 8 weeks of treatment
8. To obtain exome and transcriptome findings with other omics to identify efficacy subgroups in the two treatment arms
9. To stratify participants based on response to aripiprazole and esketamine based on immune activation and inflammation profiles using multiple plasma markers
10. To analyze deep immune phenotyping
11. Classify participants according to their response to aripiprazole and esketamine based on the activity profiles of the most relevant pathways

Conditions and MedDRA coding

Refractory major depression disorder (RMDD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients between 60-74 years
2. To be receiving antidepressant treatment that includes an an SSRI (Selective Serotonin Reuptake Inhibitors) /SNRI (Serotonin–norepinephrine reuptake inhibitors) at the time of screening that is not responding (less than 25% improvement in symptoms) after receiving an adequate dose [SmPC; or local equivalent, if applicable] for at least 6 weeks and have been increased to the dose maximum allowed
3. Current antidepressant treatment must have been immediately preceded by failure to respond to at least 3, but not more than 5, different consecutive treatments (all within the same moderately severe depressive episode) with antidepressant drugs (AD) taken at an appropriate dose for at least least 6 weeks (3 antidepressant failures including the current one)
4. To have been treated with at least 3 different classes of antidepressants between treatments taken at appropriate doses for at least 6 weeks without response in the current moderate to severe depressive episode (including current treatment with an antidepressant)
5. To be taking a single oral antidepressant on day 1 before randomization
6. Participants who, at the time of screening, are taking a combination of antidepressants and/or rescue treatment (other than aripiprazole) for the current moderate to severe depressive episode may participate in the study.

Exclusion criteria 6

1. Treatment with drugs contraindicated with the use of esketamine and aripiprazole.
2. Patients in whom a high risk of suicide is detected at the screening visit, according to the criteria established by Columbia University according to the C-SSRS evaluation
3. Patients who are participating in another clinical trial with active treatment
4. Patients who do not have the capacity to consent to participation in the trial or who do not have a representative to confirm their participation
5. Hypersensitivity to any of the active ingredients of any of the branches of treatment, or to any of the excipients of its pharmaceutical form
6. Patients in whom increased blood pressure or blood pressure intracranial fluid poses a serious risk

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical response at week 8 after initiation of treatment, measured in terms of: - Remission of depressive symptoms; total score ≤10 on the MADRS scale. - Adequate clinical response, if they show a reduction of ≥50% in the total score of the MADRS scale with respect to the initial score and a score ≤4 on the CGI severity scale.

Secondary endpoints 11

1. Clinical response at week 32 after initiation of treatment, measured in terms of: - Remission of depressive symptoms; total score ≤10 on the MADRS scale. - Adequate clinical response, if they show a reduction of ≥50% in the total score of the MADRS scale with respect to the initial score and a score ≤4 on the CGI severity scale.
2. Determination of the safety profile of esketamine nasal spray and aripiprazole at week 8, as assessed by the established safety committee
3. Determination of the safety profile of esketamine nasal spray and aripiprazole at week 32 in those patients who were relapse-free at week 8, as assessed by the established safety committee
4. Proportion of patients free of relapse at week 24 and week 32 in the group of patients with clinical remission at week 8.
5. Score on the EuroQol-5D (EQ-5D) scale for health-related quality of life in adults
6. Whole genome sequencing of trial participants using variant filtering and prioritization routinely performed in the HUVR laboratory.
7. Obtaining the transcriptome of trial participants at week 8 and week 32 of treatment using a large-scale sequencer
8. Integration of participants’ exome and transcriptome findings with other omics.
9. To determine the immune activation and inflammation profiles in both treatment groups
10. Deep immunophenotyping by flow cytometry of peripheral blood cells in both treatment groups
11. Determine the activity profiles of relevant pathways in both treatment arms

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Sponsor organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Address

Avenida De Manuel Siurot Sn

City

Sevilla

Postcode

41013

Country

Spain

Scientific contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Clinical Trial Unit IBIS/University Hospital Virgen del Rocío

Public contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Clinical Trial Unit IBIS/University Hospital Virgen del Rocío

Locations

1 EU/EEA country · 11 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

Documents 12 files

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

Application history

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