Compare the Efficacy and Safety of KH607 Tablets Versus Vortioxetine Hydrobromide Tablets in Adult Patients With Major Depressive Disorder

Официальное название

Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel-Controlled Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of KH607 Tablets in the Treatment of Major Depressive Disorder With Vortioxetine Hydrobromide Tablets as the Active Control

Обзор

This trial includes a short-term study and a long-term study. The short-term study is a multicenter, randomized, double-Blind, double-Dummy, Parallel-Controlled study with a 6-week duration. The long-term study is a withdrawal follow-up study; participants meeting relapse criteria may receive one cycle of KH607 Tablets treatment.

Подробное описание

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, double-Dummy parallel-group design, including a 14-day screening period, 6-week double-blind treatment period; the experimental group receives KH607 tablets for 3 weeks, followed by KH607 placebo for 3 weeks; the control group receives vortioxetine hydrobromide tablets for 6 weeks. In the long-term study, participants will return to the study site for follow-up every 4 weeks for up to 24 weeks. Those who do not meet relapse criteria will receive no antidepressant treatment, while participants meeting relapse criteria will be treated with KH607 Tablets for one cycle.

Вмешательства

• Препарат KH607 tablets
  oral 20mg, once daily for 21 days.
• Препарат Vortioxetine Hydrobromide Tablets
  oral 10mg, once daily for 42 days.
• Препарат Part B: KH607
  oral 20mg, once daily for 21 days.

Первичные конечные точки

• short-term study: Change From Baseline in the Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score [Срок оценки: Baseline to Day 22]

Вторичные конечные точки (12)

• short-term study: Change From Baseline in the MADRS Total Score [Срок оценки: Baseline up to Day 42]
• short-term study: Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) Total Score [Срок оценки: Baseline up to Day 42]
• short-term study: Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score [Срок оценки: Baseline up to Day 42]
• short-term study: Change from baseline in Clinical Global Impressions-Severity (CGI-S) score [Срок оценки: Baseline up to Day 42]
• short-term study: Change in Clinical Global Impressions-Improvement (CGI-I) score [Срок оценки: Baseline up to Day 42]
• short-term study: Percentage of Participants With HAM-D Response [Срок оценки: Day 4,8,15,22,28,42]
• short-term study: Percentage of Participants With HAM-D Remission [Срок оценки: Day 4,8,15,22,28,42]
• short-term study: Percentage of Participants With MADRS Response [Срок оценки: Day 4,8,15,22,28,42]
• short-term study: Percentage of Participants With MADRS Remission [Срок оценки: Day 4,8,15,22,28,42]
• short-term study: Number of Participants with Adverse Events [Срок оценки: Baseline up to Day 42]
• short-term study: Number of Participants with Suicidality Assessment using Columbia-Suicide Severity Rating Scale (C-SSRS) [Срок оценки: Baseline up to Day 42]
• short-term study: Change from Baseline in Physician Withdrawal Checklist (PWC-20) total score [Срок оценки: Baseline up to Day 42]

Критерии участия

Критерии включения

• Age: 18 to 65 years old (inclusive), Male or female.
• 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
• Depressive episode confirmed by the Mini International Neuropsychiatric Interview Version 7.0.0 (M.I.N.I. 7.0.0).
• Patients must have a Montgomery and Åsberg Depression Rating Scale (MADRS) total score ≥26, 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
• Body weight ≥45.0 kg for females or ≥50.0 kg for males, with a body mass index (BMI) ≥19 kg/m²
• Participants who is taking antidepressants must have stopped for 7 days or 5 half-lives of the antidepressant prior to Day 1.
• Participant is willing to stop other antidepressants, antipsychotics, mood stabilizers, sedatives and hypnotics during the trial.
• Fully understand the procedures and sigh the informed consent.

Only for long-term trials:

• Subjects who complete the short-term trial (Visit 8 completion), have a ≥50% reduction from short-term trial baseline in MADRS total score at Visit 8, and volunteer to enter the long-term trial.

Критерии исключения

• 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.
• A reduction of ≥25% in MADRS 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).
• Participants with clinically significant risk of suicide or self-harm, defined as any of the following:

• A score ≥4 on Item 10 (Suicidal Thoughts) of the MADRS;
• 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).
• Participants meeting any of the following depressive disorder diagnoses:

• 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);
• Depressive disorder secondary to other psychiatric disorders or somatic diseases (e.g., depression induced by hypothyroidism);
• Substance/medication-induced depressive disorder.
• 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.
• 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).
• 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).
• Use of any strong CYP3A4 inhibitor or inducer within 14 days (or 5 half-lives, whichever is longer) prior to enrollment.
• 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.
• 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.
• 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).
• Severe hypothyroidism (TSH ≥10.0 mIU/L).
• Participants with current obstructive sleep apnea and/or narcolepsy.
• Participants who have known or suspected hypersensitivity to vortioxetine hydrobromide, the investigational product or their excipients, or those with allergic diathesis (defined as allergy to at least two different substances).
• Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test at screening.
• 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.
• 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.
• History of seizures, or any other medical conditions associated with an increased seizure risk (e.g., stroke, severe head trauma, significant metabolic disturbances).
• History of narrow-angle glaucoma or other conditions resulting in elevated intraocular pressure.
• Any other conditions that, in the Investigator's opinion, render the subject unsuitable for participation in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07741331 · KH607-60102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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