Major Depressive Disorder (MDD)
Conditions
Brief summary
This trial includes a short-term study and a long-term study. The short-term study is a multicenter, randomized, double-blind, placebo-controlled parallel-group study with a 6-week duration. The long-term study is a multicenter, open-label, single-arm study with a maximum duration of 27 weeks.
Detailed description
This trial consists of two parts: a short-term study and a long-term study. The short-term study adopts a multicenter, randomized, double-blind, placebo-controlled parallel-group design, including a 14-day screening period；a 3-week double-blind treatment period, and a 3-week off-drug follow-up period. The long-term study uses a multicenter, open-label, single-arm design. Subjects who complete all study procedures of the short-term study and achieve a ≥50% reduction in the 17-item Hamilton Depression Rating Scale (HAM-D17) score at the end of the short-term study will be eligible to enter the long-term study. All enrolled subjects will receive repeated treatment with KH607 Tablets. The dosing regimen is 20 mg KH607 Tablets administered orally once every night before bedtime. A treatment course consists of 21 consecutive days of dosing, with an interval of no less than 6 weeks between two courses. Subjects may receive a maximum of 3 treatment cycles, and the maximum duration of the long-term study is 27 weeks.
Interventions
DRUGKH607 tablets
oral 20mg, once daily for 21 days
DRUGplacebo
oral, once daily for 21 days
Sponsors
Chengdu Kanghong Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18 to 65 years old (inclusive), Male or female. 2. Based on investigator's clinical assessment, study participants meet the diagnostic criteria for Major Depressive Disorder (MDD) as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with a diagnosis of single episode or recurrent episodes (ICD-10 codes: 296.2/296.3), without psychotic features. For patients with first-episode depression, the current episode must have a duration of ≥3 months; for patients with recurrent depression, the current depressive episode must have a duration of ≥1 month 3. Depressive episode confirmed by the Mini International Neuropsychiatric Interview Version 7.0.0 (M.I.N.I. 7.0.0). 4. Patients must have a 17-item Hamilton Depression Rating Scale (HAM-D17) total score ≥24, a Clinical Global Impression-Severity (CGI-S) score ≥4, and a score ≥2 on Item 1 (Depressed Mood) of the HAM-D17 at screening and baseline 5. Body weight ≥45.0 kg for females or ≥50.0 kg for males, with a body mass index (BMI) ≥19 kg/m² 6. Participants who is taking antidepressants must have stopped for 7 days or 5 half-lives of the antidepressant prior to Day 1. 7. Participant is willing to stop other antidepressants, antipsychotics, mood stabilizers, sedatives and hypnotics during the trial. 8. Fully understand the procedures and sigh the informed consent. Only for long-term studys: 9. Participants who complete the short-term study (Visit 8 completion), have a ≥50% reduction from short-term study baseline in HAM-D17 total score at Visit 8, and volunteer to enter the long-term study. Key
Exclusion criteria
1. Other psychiatric disorders meeting DSM-5 criteria, including but not limited to schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, panic disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, anorexia nervosa and bulimia nervosa, neurodevelopmental disorders, schizoaffective disorder, or any other psychiatric disorder that, in the Investigator's judgment, may compromise subject compliance. 2. A reduction of ≥25% in HAM-D17 total score at baseline compared with the screening visit (this criterion does not apply if baseline and screening assessments are performed at the same visit). 3. Participants with clinically significant risk of suicide or self-harm, defined as any of the following: 1. A score ≥4 on Item 10 (Suicidal Thoughts) of the MADRS; 2. An answer of "Yes" to Question 4 (active suicidal ideation with intent without specific plan) or Question 5 (active suicidal ideation with specific plan and intent) of the C-SSRS within the past 6 months at screening, or a suicide-related behavior within the past 6 months (any "Yes" response for Actual Attempt, Interrupted Attempt, or Aborted Attempt). 4. Participants meeting any of the following depressive disorder diagnoses: 1. Poor response to adequate dose and adequate duration (at least 6 weeks) of two or more antidepressants with distinct pharmacological mechanisms during a prior depressive episode (based on Investigator interview, to be adjudicated and documented by the Investigator); 2. Depressive disorder secondary to other psychiatric disorders or somatic diseases (e.g., depression induced by hypothyroidism); 3. Substance/medication-induced depressive disorder. 5. Participants receiving structured psychotherapy (interpersonal therapy, psychodynamic therapy, cognitive behavioral therapy, etc.), music therapy, exercise therapy, acupuncture, or other therapies from screening through baseline, who require continuation of such therapies during the study. 6. Receipt of depression-related neuromodulation therapies within 1 month prior to enrollment, including but not limited to modified electroconvulsive therapy (MECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS). 7. Prior use of atypical antipsychotics or mood stabilizers during the current depressive episode (e.g., olanzapine, risperidone, quetiapine, aripiprazole, brexpiprazole, ziprasidone, cariprazine, valproate, lithium carbonate). 8. Use of any strong CYP3A4 inhibitor or inducer within 14 days (or 5 half-lives, whichever is longer) prior to enrollment. 9. Abnormal hepatic or renal function prior to enrollment: liver function abnormalities (ALT or AST \>2×ULN), renal function abnormalities (Cr \>1.5×ULN), or other conditions deemed inappropriate for enrollment by the Investigator. 10. Positive test results at screening for active hepatitis B (HBV-DNA ≥1000 copies/mL or 200 IU/mL), hepatitis C antibody, syphilis antibody, or human immunodeficiency virus (HIV) antibody. 11. 12-lead electrocardiogram (ECG) showing second-degree or third-degree atrioventricular block, long QT syndrome, or QTcF \>450 ms (male) / 460 ms (female) prior to enrollment; or other conditions unsuitable for participation as judged by the Investigator (e.g., clinically significant tachyarrhythmia requiring intervention). 12. Severe hypothyroidism (TSH ≥10.0 mIU/L). 13. Participants with current obstructive sleep apnea and/or narcolepsy. 14. Known or suspected history of hypersensitivity to the investigational product or its excipients, or participants with multiple allergies (defined as allergies to at least 2 different substances). 15. Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test at screening. 16. Participants or their partners planning pregnancy, sperm donation, or oocyte donation during the study and within 6 months after the last study drug administration, and unwilling to use adequate and effective contraception throughout this period. 17. Participants who cannot avoid driving, operating hazardous machinery, or working at heights from the first dose of study drug until 2 weeks after the last dose. 18. Any other conditions that, in the Investigator's opinion, render the subject unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double Blind (DB) Treatment Phase: Change from Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D17) Total Score in Participants with Major Depressive Disorder | Baseline up to Day 22 | The HAM-D is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment.HAM-D17 total score comprised a sum of 17 individual item scores.The total score could range from 0 to 52. Higher scores indicated a greater degree of depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double Blind (DB) Treatment Phase: Change from Baseline in HAM-D17 Total Score in Participants with Major Depressive Disorder | Baseline up to Day 42 | The HAM-D is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment.HAM-D17 total score comprised a sum of 17 individual item scores.The total score could range from 0 to 52. Higher scores indicated a greater degree of depression. |
| Double Blind (DB) Treatment Phase: Change from Baseline in the Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score | Baseline up to Day 42 | The MADRS was a ten-item diagnostic questionnaire which psychiatrists used to measure the severity of depressive episodes in participants with mood disorders. Each item yielded a score of 0 to 6. The MADRS total score was calculated as the sum of the 10 individual item scores, which ranged from 0 to 60. Higher MADRS scores indicated more severe depression. |
| Double Blind (DB) Treatment Phase: Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score | Baseline up to Day 42 | The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Scoring for HAM-A was calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56. The HAM-A total score was calculated as the sum of the 14 individual item scores. |
| Double Blind (DB) Treatment Phase: Change from Baseline in Clinical Global Impressions-Severity (CGI-S) score | Baseline up to Day 42 | The CGI-S item employed a 7-point Likert scale to measure the overall severtity in the participant's condition. |
| Double Blind (DB) Treatment Phase:Change in Clinical Global Impressions-Improvement (CGI-I) score | Baseline up to Day 42 | The CGI-I item employed a 7-point Likert scale to measure the overall improvement in the participant's condition post-treatment. The CGI-I was only rated at post-treatment assessments. |
| Double Blind (DB) Treatment Phase:Percentage of Participants With HAM-D Response | Baseline up to Day 42 | HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. |
| Double Blind (DB) Treatment Phase: Percentage of Participants With HAM-D Remission | Baseline up to Day 42 | HAM-D remission was defined as having a HAM-D total score of ≤7. |
| Double Blind (DB) Treatment Phase: Percentage of Participants With MADRS Response | Baseline up to Day 42 | MADRS response was defined as having a 50% or greater reduction from baseline in MADRS total score. |
| Double Blind (DB) Treatment Phase: Percentage of Participants With MADRS Remission | Baseline up to Day 42 | MADRS remission was defined as having a MADRS total score of ≤10. |
| Double Blind (DB) Treatment Phase: Number of Participants with Adverse Events | Baseline up to Day 42 | An AE is any untoward medical occurrence in a clinical study participant administered with a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
| Double Blind (DB) Treatment Phase: Number of Participants with Suicidality Assessment using Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline up to Day 42 | The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed to assess severity and track suicidal events through any treatment. The C-SSRS scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. |
| Double Blind (DB) Treatment Phase: Change from Baseline in Physician Withdrawal Checklist (PWC-20) total score | Baseline up to Day 42 | The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms. |
| Open-Label (OL) Treatment Phase: Number of Participants with Adverse Events | OL Baseline (Day 42) up to 27 weeks | An AE is any untoward medical occurrence in a clinical study participant administered with a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
| Open-Label (OL) Treatment Phase: Time from OL Baseline (Day 42) to the First Relapse in Participants | OL Baseline (Day 42) up to 27 weeks | Time from OL Baseline (Day 42) to the first relapse will be reported. |
| Open-Label (OL) Treatment Phase: Proportion of participants receiving different numbers of treatment cycles within 27 weeks | OL Baseline (Day 42) up to 27 weeks | Proportion of participants receiving different numbers of treatment cycles |
| Open-Label (OL) Treatment Phase: Change from Baseline in HAM-D17 total score | OL Baseline (Day 42) up to 27 weeks | The HAM-D is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment.HAM-D17 total score comprised a sum of 17 individual item scores.The total score could range from 0 to 52. Higher scores indicated a greater degree of depression. |
| Open-Label (OL) Treatment Phase: Change from Baseline in MADRS total score | OL Baseline (Day 42) up to 27 weeks | The MADRS was a ten-item diagnostic questionnaire which psychiatrists used to measure the severity of depressive episodes in participants with mood disorders. Each item yielded a score of 0 to 6. The MADRS total score was calculated as the sum of the 10 individual item scores, which ranged from 0 to 60. Higher MADRS scores indicated more severe depression. |
| Open-Label (OL) Treatment Phase: Change from Baseline in HAM-A total score | OL Baseline (Day 42) up to 27 weeks | The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Scoring for HAM-A was calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56. The HAM-A total score was calculated as the sum of the 14 individual item scores. |
| Open-Label (OL) Treatment Phase: Change from Baseline in CGI-S | OL Baseline (Day 42) up to 27 weeks | Open-Label (OL) Treatment Phase: Change from Baseline in CGI-S |
| Open-Label (OL) Treatment Phase: Change in CGI-I score | OL Baseline (Day 42) up to 27 weeks | The CGI-I item employed a 7-point Likert scale to measure the overall improvement in the participant's condition post-treatment. The CGI-I was only rated at post-treatment assessments. |
Contacts
CONTACTGang Wang, Medical Doctor
CONTACTBing Bing Fu, Medical Doctor
Outcome results
None listed