| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Major Depressive Disorder | |
| E.1.1.1 | Medical condition in easily understood language | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10081270 | | E.1.2 | Term | Major depressive disorder | | E.1.2 | System Organ Class | 100000004873 | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | The primary objective is to assess the safety and tolerability of seltorexant as adjunctive therapy to an antidepressant in adolescents with Major Depressive Disorder (MDD) in the short-term compared with placebo | |
| E.2.2 | Secondary objectives of the trial | The main secondary objectives are
• To assess the efficacy of seltorexant on symptoms of MDD compared with placebo as adjunctive therapy to an antidepressant
• To assess the efficacy of seltorexant on symptoms of sleep compared with placebo as adjunctive therapy to an antidepressant
• To investigate the pharmacokinetics (PK) of seltorexant as adjunctive therapy to an antidepressant in adolescents with MDD
For the full list, please refer to the protocol. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Each potential participant must satisfy all of the following criteria to be enrolled in the study:
Age
1. Male or female, aged 12 to <18 years at screening.
Type of Participant and Disease Characteristic
2. Must meet DSM-5 diagnosis of MDD without psychotic features.
3. Has inadequate response to at least 1, but no more than 2 antidepressant treatments during the current major depressive episode including their current antidepressant (SSRI).
4. Has had at least 6 sessions of psychotherapy in this episode prior to randomization.
5. Must have Children's Depression Rating Scale-Revised (CDRS-R) total score ≥48 at the beginning of screening with no more than a 25% improvement during screening.
6. Must be otherwise healthy on the basis of physical examination, medical history, vital signs, 12-lead ECG, and clinical laboratory tests performed at screening.
Weight
7. Participants weighing between 5th and 95th percentile for age and sex with baseline weight is ≥30 kg.
For the full list of inclusion criteria, please refer to the protocol. | |
| E.4 | Principal exclusion criteria | Any potential participant who meets any of the following criteria will be excluded from participating in the study:
Medical Conditions
● Has current active DSM-5 diagnosis of obsessive-compulsive disorder, post-traumatic stress disorder, anorexia nervosa or bulimia nervosa. A prior history of one or more of these disorders is allowed as long as the disorder(s) have been in remission for at least 6 months. Stable Attention deficit/hyperactive disorder (ADHD/ADD) is allowed. Comorbid anxiety disorders are allowed.
● Has history or current diagnosis of psychotic disorder, bipolar disorder, conduct disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, somatoform disorders, or fibromyalgia.
● Has a significant primary sleep disorder confirmed by PSG assessment at screening for participants in subgroup, but participants with insomnia or hypersomnia disorders are allowed.
● At significant risk of committing suicide based on history or according to the investigator's experience, or based on active suicidal ideation, intent or plan, item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past 3 months or a history of suicidal behavior within the last 6 months.
● Has a history of moderate to severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening or positive test result(s) for alcohol and/or drugs of abuse.
● Has known allergies, hypersensitivity, or intolerance to seltorexant or its excipients.
For the full list of exclusion criteria, please refer to the protocol.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | 1. TEAEs, adverse events of special interest (AESI), Pediatric Adverse Event Rating Scale (PAERS)
2. Clinical laboratory values and electrocardiogram (ECG)
3. Vital signs and physical examination including weight
4. Suicidality assessment using the Columbia Suicide Severity Rating Scale (C SSRS)
5. Withdrawal symptoms assessment using the Physician Withdrawal Checklist (PWC-20) on stopping study intervention
6. Menstrual cycle tracking
| |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | 1. Continuous throughout the study
2 and 6. Screening, baseline and week 6
3 and 4. Screening, baseline, weeks 1, 2, 4, 6 and at follow up
5. Baseline, week 6 and at follow up
| |
| E.5.2 | Secondary end point(s) | 1. Change from baseline to Week 6/EOT in the CDRS total score
2. Change from baseline to Week 6 in the MADRS total score
3. Change from baseline over time in the Clinical Global Impression-Severity (CGI S) score
4. Change from baseline to Week 6/EOT on subjective sleep assessment (PROMIS-Pediatric-SD (Short Form 8a))
5. Change from baseline to Week 6/EOT on objective sleep assessment actigraphy
6. Sparse PK sampling in all participants. Optimal PK sampling in a subgroup of participants
For the full list, please refer to the protocol.
| |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | 1. Screening, baseline, weeks 1, 2, 4, 6 and at follow up
2 . Baseline, weeks 2 and, 4 and 6
3 and 4. Baseline, weeks 1, 2, 4, 6 and at follow up
5. Continuous throughout the study
6. Week 6 | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | | Tolerability and Biomarker evaluation | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description | | Safety, Tolerability, and Pharmacokinetics of Seltorexant in the adolescent MDD population | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | Will this trial be conducted at a single site globally? | No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned | | Italy | | Spain | | United Kingdom | | United States | |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 24 |
