A Study of KH607 as Monotherpy in Adults Participants With Major Depressive Disorder

Official title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of KH607 Tablets in the Treatment of Major Depressive Disorder

Overview

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

• Drug KH607 tablets
  oral 20mg, once daily for 21 days
• Drug placebo
  oral, once daily for 21 days
• Drug KH607 tablets
  oral 20mg, once daily for 21 days

Primary outcome measures

• 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 [Time frame: Baseline up to Day 22]

Secondary outcome measures (12)

• Double Blind (DB) Treatment Phase: Change from Baseline in HAM-D17 Total Score in Participants with Major Depressive Disorder [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Change from Baseline in the Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Change from Baseline in Clinical Global Impressions-Severity (CGI-S) score [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase:Change in Clinical Global Impressions-Improvement (CGI-I) score [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase:Percentage of Participants With HAM-D Response [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Percentage of Participants With HAM-D Remission [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Percentage of Participants With MADRS Response [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Percentage of Participants With MADRS Remission [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Number of Participants with Adverse Events [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Number of Participants with Suicidality Assessment using Columbia-Suicide Severity Rating Scale (C-SSRS) [Time frame: Baseline up to Day 42]
• Double Blind (DB) Treatment Phase: Change from Baseline in Physician Withdrawal Checklist (PWC-20) total score [Time frame: Baseline up to Day 42]

Eligibility criteria

Inclusion criteria

• 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 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
• 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 studys:

• 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.

Exclusion criteria

• 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 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).
• 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.
• 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).
• 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.
• Any other conditions that, in the Investigator's opinion, render the subject unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07741240 · KH607-60101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗