Efficacy and Safety of REL-1017 for Major Depressive Disorder

Prior treatment

• Any long-term use (ie, >120 days in a 6-month period) of prescribed opioids or controlled substances within 6 months, prior to Screening – as verified by appropriate medical records.
• More than 3 doses of opioids use within 30 days prior to Baseline
• Pro Re Nata (PRN) use of any anxiolytic, antipsychotic, anticonvulsant/antiepileptic, mood stabilizer, or stimulant medications or supplements within 30 days prior to Screening. Note: Participants should be medically stable; when discontinuation of a prohibited medication is indicated, the prohibited medication should be appropriately tapered to avoid withdrawal symptoms. Benzodiazepines, atypical antipsychotic drugs, anticonvulsants/antiepileptic drugs, mood stabilizers, stimulants, and supplements, including St. John’s Wort, [Hypericum Perforatum), taken regularly and daily at a stable dose for at least six weeks prior to Screening, for the treatment of MDD or its symptoms, are permitted.

Other illness

• Any medical, psychiatric condition, or social context that, in the opinion of the investigator, is likely to unfavourably alter the risk-benefit of participant, to interfere with protocol compliance, or to confound safety or efficacy assessments

Lab values

• History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the Investigator would jeopardize the safety of the participant or the validity of the study results.
• Poorly controlled diabetes as defined by a glycosylated hemoglobin (HbA1c) >8.5% (69 mmol/mol), despite standard care. (Note: re-screening of patients who has failed the screening process due to not meeting this exclusion criterion is allowed after diabetes treatment adjustment and level of glycosylated hemoglobin (HbA1c) back to <8.5%)

Other

• Triplicate 12-lead ECG with average QTcF ≥450 msec, and/or a QRS interval ≥120 msec at Screening

• Written informed consent.
• As ascertained by an independent adjudicator, the data transcribed in the eCRF from the ATRQ, SCID-5-CV, PHQ9, MADRS, C-SSRS, HAM-A are complete, consistent and compatible with the primary diagnosis of moderate to severe MDD with inadequate response to an adequate trial of antidepressants as defined in the criterion above. • A cut-off of ≥ 26 on MADRS is defined for study entry. The remaining scales will be checked by the independent adjudicator only for ensuring consistency of diagnosis for inclusion of patients, i.e. diagnosis of MDD as defined by the DSM-5.
• Baseline (Day 1) MADRS10 score not exceeding >30% and <20% compared to the Screening MADRS
• Male or female participant, aged 18 to 65 years, inclusive.
• Body mass index (BMI) between 18.5 and 30.0 kg/m2, at Screening
• Participant understands the study requirements, is willing and able to commit to meet all study requirements, adhere to both approved ADT and study drug regimen, and complete all assessments and all scheduled visits, per Investigator judgment
• Women of childbearing potential (WOCBP) and men whose sexual partners are WOCBP must use at least 1 highly effective method of contraception from Screening and for at least 2 months after the last study drug administration
• Diagnosed with MDD as defined by the Diagnostic and Statistical Manual, Fifth Edition (DSM-5), and confirmed by the SCID-5 CV.
• Diagnosed with a current MDE lasting from 8 weeks to 24 months as defined by the DSM-5 and confirmed by the SCID-5 CV, as well as confirmation of MADRS10 and PHQ9 scores of moderate to severe MDD and contextual appropriateness to be a participant in this study by the Investigator.
• Diagnosed with a current MDE lasting from 8 weeks to 24 months as defined by the DSM-5 and confirmed by the SCID-5 MDD, as well as confirmation of MADRS10 score, ATRQ, and contextual appropriateness to be a participant in this study by the Investigator
• Treated for at least 6 weeks prior to Screening, stabilized for at least 6 weeks prior to Baseline, and experiencing approximately 10% to 50% improvement, as assessed by the clinician, and documented on the ATRQ, from an approved dosing regimen of ADT (eg, SSRI, SNRI, bupropion [a NDRI and nicotinic receptor antagonist] or atypical antipsychotic adjunctive antidepressant, alone or in combination) during the current MDE, and committed to remaining on the same stable dosing regimen for the Screening period and for the entire study, at or above the minimally adequate dose listed in the ATRQ. Subjects with clinician assessed antidepressant tolerance/tachyphylaxis are eligible even if the current ADT response is <10%.