A Randomized, 52-Week Extension Study to Evaluate the Maintenance of Remission, Relapse Prevention, and Long-Term Safety of CreNeuroS™ in Patients With Major Depressive Disorder Who Achieved Remission Following an 8-Week Parent Study

Prior treatment

• Subject requires continuation, reinstatement or initiation of antidepressant therapy due to clinical deterioration.
• Requirement for prohibited concomitant medications or therapies that may interfere with the study assessments.

Other illness

• Any new or worsening medical or psychiatric condition that, in the Investigator's opinion, makes the subject unsuitable for participation.
• Emergence of clinically significant suicidal ideation, suicidal behaviour or other safety concern requiring therapeutic intervention or a higher level of psychiatric care.
• Any other condition or circumstance that, in the Investigator's judgment, makes the subject unsuitable for participation or places the subject at unacceptable risk.
  • Relapse is defined as meeting ALL of the following criteria simultaneously: (1) HAM-D-17 score ≥18; (2) and an increase of ≥50% from the baseline score; (3) and hospitalization or adjustment of antidepressant treatment (e.g., change in medication) due to worsening depressive symptoms, as determined by the Investigator.

Other

• HAM-D-17 score \>7 at Week 8 of the parent study.
• Clinically significant worsening of depressive symptoms during the Escitalopram taper/transition period that, in the Investigator's opinion, makes participation inappropriate.
• Subject meets the protocol-defined criteria for relapse during the transition/taper period or before extension enrollment.
• Clinically significant Escitalopram discontinuation/withdrawal symptoms requiring continued antidepressant treatment or otherwise precluding participation in the extension.
• Any ongoing clinically significant adverse event or serious adverse event that may compromise subject safety or interfere with assessment of the extension outcomes.
• Major protocol deviation during the parent study that, in the Investigator's opinion, may affect subject safety or the reliability of the extension assessments.
• Pregnancy, planned pregnancy during the extension period, or breastfeeding, as applicable.
• Significant non-compliance with study procedures, treatment or visits during the parent study that raises concern regarding the subject's ability to comply with the extension.
• Subject withdraws consent or is unwilling to continue participation.
• Subject is unlikely to be available for the required 52-week follow-up or unable to comply with the study procedures.

• Subject has completed the 8-week treatment phase of the parent study and achieved remission, defined as HAM-D-17 ≤7 at Week 8.
• Subject is clinically stable at the time of entering the transition/taper period, with no clinically significant worsening of depressive symptoms requiring immediate therapeutic intervention.
• Investigator considers tapering and discontinuation of Escitalopram clinically appropriate and safe for the subject.
• Subject completes the protocol-defined Escitalopram taper/transition period without experiencing relapse or clinically significant worsening of depressive symptoms requiring therapeutic intervention.
• Following completion of the transition period, subject remains clinically suitable for participation based on Investigator assessment, including depressive symptoms and overall clinical status, and has not experienced relapse during the transition/taper period.
• Subject does not require continuation, reinstatement or initiation of antidepressant therapy at the time of extension enrollment, except protocol-permitted rescue treatment where applicable.
• Subject has no clinically significant adverse event, serious adverse event, or new medical/psychiatric condition that would preclude participation.
• Subject is willing and able to comply with the 52-week maintenance visits, assessments, treatment requirements and other study procedures.
• Subject provides written informed consent for participation in the Extension/Maintenance Phase before undertaking any extension-specific study procedure.
• Subject is considered medically and psychiatrically suitable for participation in the 52-week extension by the Investigator.