Overview
This multicenter, randomized, open-label extension study will evaluate the maintenance of remission, relapse prevention, long-term clinical outcomes, and safety of CreNeuroS™ in participants with Major Depressive Disorder (MDD) who achieve protocol-defined remission (HAM-D-17 score ≤7) following completion of the 8-week acute treatment phase of parent study VRL-CT-26-006.
Eligible participants who remain clinically stable and provide written informed consent for the extension study will undergo a transition/taper period of approximately 2 weeks, which may be extended to 4 weeks if clinically warranted. No extension study intervention will be administered during this period.
Following the transition/taper period, eligible participants will be randomized in a 1:1:1 ratio to one of three maintenance groups: (1) observation without CreNeuroS™ supplementation; (2) CreNeuroS™ CNS Fish Oil Plus Softgels, one capsule orally once daily; or (3) CreNeuroS™ CNS Fish Oil Plus Softgels, two capsules orally once daily. Participants will be followed for 52 weeks after extension baseline to assess maintenance of remission, relapse, clinical outcomes, and safety.
Description
The parent study had randomized 80 subjects. Based on the anticipated remission rate following the 8-week acute treatment phase, it is expected that approximately 50 to 70 subjects will be eligible for participation in the extension phase. The actual number of subjects enrolled will depend on the observed remission rate, subject willingness to continue participation, and investigator assessment of eligibility.
The extension phase is intended to generate long-term evidence on the maintenance of remission, prevention of relapse, and long-term safety of CreNeuroS™ CNS Fish Oil Plus Softgels.
Eligibility
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Subject requires continuation, reinstatement or initiation of antidepressant therapy due to clinical deterioration.
- 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.
- 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.
- Major protocol deviation during the parent study that, in the Investigator's opinion, may affect subject safety or the reliability of the extension assessments.
- Requirement for prohibited concomitant medications or therapies that may interfere with the study 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.
- 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.
