This study is testing a new medicine called **CLE-100 (oral esketamine)** to see if it helps people with **Major Depressive Disorder (MDD)** who don't respond well to regular antidepressants. MDD is a condition where people feel very sad or hopeless for a long time. The study is in **Phase 2**, meaning it's still being tested to check if it's safe and works well. Participants will take CLE-100, or a fake pill (placebo), once a day for four weeks along with their regular medicine. If they feel better after this, they can continue taking CLE-100 for six more months.

• You need to visit the study site regularly for check-ups.
• The study lasts 4 weeks, with a possible 6-month extension if it helps.
• Participants will not know if they receive CLE-100 or a placebo.

To join, you must be 18-65 years old, currently taking an antidepressant, and not have responded to at least two different ones. You can't join if you've tried more than five different antidepressants without success or have very high risks of suicide, among other conditions.