Major depressive disorder (MDD) Mental and Behavioural Disorders
Conditions
Interventions
There are two treatment arms in this double-blinded study. Participants will take either tildacerfont (the study drug) or placebo. At least 88 participants will take part in this study. Half of the pa
Sponsors
MAC Clinical Research
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Able to comprehend and willing to sign an ICF and to comply with all aspects of the trial 2. Male or female 3. Aged between 18 to 65 years (inclusive) at the date of informed consent 4. Body mass index (BMI) of 18 to 35 kg/m2, inclusive 5. CRHR1CDx-positive 6. Outpatients 7. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) diagnostic criteria for MDD (moderate or severe, single or recurrent episode, with or without psychotic features [International Classification of Diseases (ICD)-10-CM codes F32.1, F32.2, F32.3, F33.1, F33.2, F33.3]), confirmed by the Mini-International Neuropsychiatric Interview (MINI). Participants with the following co morbid conditions can be included (secondary diagnosis), as long as the primary diagnosis is MDD: 7.1. Anxiety disorders, e.g. generalised anxiety disorder (GAD) or panic disorder 7.2. Post-traumatic stress disorder (PTSD) 7.3. Obsessive-compulsive disorder (OCD), if the current episode is not impairing/disabling or interfering with the participant’s adherence to trial medication intake and the trial protocol 7.4. Eating disorders, if the condition does not impact the efficacy of the trial medication or raise safety concerns in the Investigator’s opinion 7.5. Attention deficit hyperactivity disorder (ADHD), if the participant is able to maintain adequate levels of concentration to consent to the trial and undergo the trial assessments, and does not require pharmacological intervention 8. MADRS score =25 at screening and baseline 9. Duration of current episode no longer than 12 months prior to screening 10. Symptoms of depression present for at least 2 weeks prior to screening 11. Willingness to stop prohibited psychotropic medication at least 7 days or 5 half-lives, whichever is longer, before baseline (Visit 2). When needed as sleeping or anti-anxiety medication, selected benzodiazepines and non-benzodiazepines are permitted as specified in Appendix 3 12. Male participants must use a condom during the trial from screening until 90 days after their final dose of trial medication, if their partner is a female of childbearing potential. In addition, their partner of childbearing potential must use an additional method of highly effective contraception (see Section 6.3.1 for highly effective methods of contraception) from screening until 90 days following final dosing Note: Throughout this Protocol, the use of male/female refers to the biological gender assigned at birth. Note: If the male participant or partner is vasectomised (and the absence of sperm has been confirmed) then this will be accepted as a form of highly effective contraception, in addition to the male also wearing a condom 13. Female participants: 13.1. Of childbearing potential must agree to use a highly effective method of contraception (see Section 6.3.1 for highly effective methods of contraception) in combination with their male partner’s use of a condom from screening until 30 days after their final dose of trial medication. Participants must have a negative pregnancy test at Visit 1 and Visit 2. 13.2. Of nonchildbearing potential (i.e., postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy). A postmenopausal state is defined as spontaneous amenorrhoea for at least 12 months without an alternative cause, and a serum FSH level within the menopausal range (=40 mIU/mL), unless the participant is taking hormone repla
Exclusion criteria
Exclusion criteria: 1. A CRHR1CDx-negative result 2. Currently ongoing psychiatric and neurological concomitant condition 3. Significant risk of suicide 4. Unable to complete or tolerate wash-out from current antidepressant medication (if applicable). Participants who are able to wash out but require a longer wash-out period that is not considered appropriate will be excluded 5. Wash-out of existing antidepressant medication (if applicable) is considered unsuitable for the participant (e.g., participant is receiving benefit from their existing antidepressant treatment in the opinion of the Investigator, or the risks of discontinuation outweigh the benefit of participating in the trial) 6. Known or suspected lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative CNS disorder, epilepsy or any other disease/procedure/accident/intervention 7. Known or suspected cardiovascular/cerebrovascular disease 8. Untreated hypertension and a systolic blood pressure >160 mmHg (at rest) and/or diastolic blood pressure >100 mmHg (at rest) at screening 9. Clinically relevant abnormal ECG findings at screening, including a QTcF =470 msec in females or =450 msec in males 10. Clinically relevant abnormal laboratory results, vital signs or physical findings at screening 11. A history of, or symptoms and signs suggestive of, impaired hepatic function or cirrhosis, including an ALT or AST value >2 × the ULN, and/or total bilirubin >1.5 × the ULN, and/or total bile acids >5 × the ULN, and/or a ratio of ALT: alkaline phosphatase (ALP) normalised to ULN for each ([ALT/ULNALT]/ [ALP/ULNALP] >5, at screening. 12. Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (anti-HCV) or human immunodeficiency virus 1 and 2 (anti-HIV 1/2) at screening 13. Cushing’s Syndrome 14. Addison’s Disease 15. Renal insufficiency 16. Uncontrolled diabetes (glycated haemoglobin [HbA1c] >8.0% at screening) or diabetes treatment ongoing for less than 3 months prior to screening 17. Known but untreated conditions causing hyperthyroidism or hypothyroidism, with the following 18. Hypopituitarism or bilateral adrenalectomy 19. Participants with any significant disease or disorder 20. A history of moderate to severe alcohol use and/or substance use disorder 21. A positive result on the urine drug screen for substances of abuse (Table 3) at screening 22. Intake of benzodiazepines during the trial is prohibited (see Appendix 3 for exceptions and restrictions) 23. A history of electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation or any experimental CNS treatment during the current episode or within 6 months prior to screening 24. Donation or loss of whole blood =500 mL within 2 weeks prior to first dosing. Blood donation during the 8 weeks of IMP intake is prohibited 25. Participants who have received an IMP or used an invasive investigational medical device in a clinical trial, within 6 months prior to screening. Use of any investigational drugs (with the exception of tildacerfont) is prohibited during the trial 26. Participation in 2 or more clinical interventional trials within 1 year prior to screening 27. Current enrolment in a clinical interventional trial 28. Female participants of childbearing potential who are pregnant, breastfeeding or planning to conceive during the course of the trial and follow-up 29. Male participant who will not abstain from sperm donation from screening until at le
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Depression measured using the Hamilton Depression Rating Scale (HAMD-17) total score at baseline, and days 7, 14, 28, and 42 | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary endpoint: Functional Impairment is measured using the Sheehan Disability Scale (SDS) from baseline to Day 56 Further secondary endpoints will be assessed at baseline and each post-baseline visit, except where stated: 1. The severity of depressive symptoms is measured using the HAMD-17 total score 2. The severity of depression symptoms is measured using the 6-item HAMD (HAMD-6) total score 3. The severity of depression symptoms is measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) 4. The severity of depression symptoms is measured using the 6-item MADRS (MADRS-6) total score 5. Response rate is measured using the HAMD-17 total score, response is defined as an at least 50% reduction in the total score of HAMD-17 compared with baseline 6. Remission rate is measured using HAMD-17 total score, remission is defined as total HAMD-17 score =7 7. Response rate is measured using total MADRS score, response is defined as at least a 50% reduction in the total score of MADRS compared with baseline 8. Remission rate is measured using the total MADRS score, remission is defined as the total MADRS score =10 9. Severity of depression is measured using the Patient Health Questionnaire-9 (PHQ-9) 10. Severity of symptoms measured using the Clinical Global Impression Scale – Severity (CGI-S) 11. Functional Impairment is measured using the Sheehan Disability Scale (SDS) 12. Health-related quality of life measured using the 5-level EQ-5D (EQ-5D-5L) 13. The number of reported adverse events (AEs) and serious adverse events (SAEs) measured using data collected from case report forms, and the number of reported clinical safety abnormalities measured using clinical laboratory evaluations and ECG 14. Plasma concentrations of tildacerfont measured using Plasma PK blood tests on days 7, 28 and 56 | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactRoss;Neel Mears;Bhatt
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Outcome results
None listed