A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study Evaluating the Efficacy and Safety of HS-10353 in Chinese Adults With Depression.

Jiangsu Hansoh Pharmaceutical Co., Ltd.0 sites144 target enrollmentAugust 31, 2023

ConditionsMajor Depressive Disorder (MDD)

InterventionsHS-10353 30mg oral capsules HS-10353 50mg oral capsules Placebo for HS-10353 30mg capsules Placebo for HS-10353 50mg capsules

DrugsHS-10353 30mg oral capsules HS-10353 50mg oral capsules Placebo for HS-10353 30mg capsules Placebo for HS-10353 50mg capsules

Overview

Phase: Phase 2
Intervention: HS-10353 30mg oral capsules
Conditions: Major Depressive Disorder (MDD)
Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Enrollment: 144
Primary Endpoint: Change From Baseline in the 17-item HAM-D Total Score at Day 15
Status: Not yet recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is a randomized, double-blind, placebo-controlled Phase II clinical study to evaluate the efficacy and safety of continuous oral administration of HS-10353 in Chinese adults with depression.HS-10353 is a new generation of GABAA receptor isomeric modulator developed by our company, which can correct the dysfunction of GABAA receptor function and restore the balance between GABA receptor and NMDA receptor. Oral administration of HS-10353 at night for 14 days is expected to reduce clinical symptoms in patients with depression. As an oral preparation of allopregnenolone analogitics, it has good bioavailability, rapid onset and high safety, and has broad clinical application prospects, which is expected to better meet the treatment needs of clinical depression in China in the future.

Registry

clinicaltrials.gov

Start Date

August 31, 2023

End Date

April 30, 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Jiangsu Hansoh Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Aged between 18 and 65 years (including the threshold);
•Subjects should have a full understanding of the test content, process and possible adverse reactions, and voluntarily sign an informed consent form (ICF);
•Participants met the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) diagnostic criteria for recurrent depressive disorder (MDD) or single episode MDD without psychotic symptoms, and had an overall HAM-D17 score ≥22;
•No antidepressant therapy has been used during the current episode; Participants who are currently taking antidepressants should be eluted for at least 1 week (or 5 half-lives, whichever is longer) before they can be included in the study.
•Agree to stop using other antidepressants, antianxiety drugs, antipsychotics, mood stabilizers, benzodiazepines sedative and hypnotic drugs during the study treatment;
•According to the investigators, the subjects were generally in good physical condition. During screening, no clinically significant abnormalities were found in physical examination, vital signs, 12-lead electrocardiogram (ECG), laboratory examination (blood routine, blood biochemistry, thyroid function, coagulation function, urine routine, etc.), anterolateral chest X-ray or chest CT.
•Female subjects of reproductive age, serum β-hCG (β-HCG) negative at screening/baseline;
•Subjects must agree to abstain from sex or use other effective contraceptive methods for 30 days from screening until the last dose; Male subjects should agree to refrain from donating sperm from the start of dosing until 6 months after stopping study treatment, and female subjects should agree to refrain from donating eggs from the start of dosing until 6 months after stopping study treatment.

Exclusion Criteria

•According to the DSM-5 diagnostic criteria, the subject has a current/past history of schizophrenia spectrum or other psychosis, bipolar or related disorders, compulsive and related disorders, trauma and stress-related disorders, dissociation disorders, anorexia or bulimia nervosa, personality disorders, etc.;
•Consistent with the diagnosis of treatment-resistant depression, that is, persistent depressive symptoms after sufficient doses and full courses of two antidepressants are used in a single depressive episode;
•Based on the Columbia-Suicide Severity Assessment Scale (C-SSRS), subjects had a history of suicidal intent/self-harm behavior during the current depressive episode;
•Use of typical/atypical antipsychotics and mood stabilizers during the current depressive episode;
•Previous history of seizures (except convulsions caused by febrile convulsions in children);
•Have a history of severe allergies;
•A history of alcohol or drug dependence/drug abuse (including benzodiazepines, other than nicotine or caffeine) within the last 1 year, or a positive urine drug test at screening;
•Take CYP3A4 suppressant or grapefruit/grapefruit juice, grapefruit/grapefruit, Sevilla orange or products rich in such substances within 14 days prior to screening (or 5 half-lives, whichever is longer);
•Use of CYP inducers such as rifampin, carbamazepine, Ritonavir, enzalutamide, efavirenan, nevirapine, phenytoin, phenobarbital, or St. John's Wort within 14 days (or 5 half-lives, whichever is longer) prior to screening;
•Received modified electroconvulsive therapy (MECT) during the current depressive episode; Or received transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS) within 1 week before screening; Or the investigator determines that the subject with the current seizure needs to receive the above treatment;

Arms & Interventions

HS-10353 Capsules

Intervention: HS-10353 30mg oral capsules

HS-10353 Capsules

Intervention: HS-10353 50mg oral capsules

HS-10353 matched-placebo oral capsules

Intervention: Placebo for HS-10353 30mg capsules

HS-10353 matched-placebo oral capsules

Intervention: Placebo for HS-10353 50mg capsules

Outcomes

Primary Outcomes

Change From Baseline in the 17-item HAM-D Total Score at Day 15

Time Frame: Baseline (BL), Day 15

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depression. A negative change from baseline indicates less depression.

Secondary Outcomes

Change From Baseline in the 17-item HAM-D Total Score(Baseline, Days 3, 8, 21,28)
Number of Participants Achieving HAM-D Response(Days 3，8，15, 21, and 28)
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score(Baseline, Days 15，28)
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) and Serious TEAE in Treatment and FU Periods(Treatment period: Up to Day 14; FU period: Day 15 to 28)
Number of Participants With Clinically Significant Vital Sign Abnormalities in Treatment and FU Periods(Up to Day 14; FU period: Day 15 to 28)
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities in Treatment and FU Periods(Up to Day 14; FU period: Day 15 to 42)
Change From Baseline in SSS Scores in Double-blind Treatment Period(Up to Day 14)
Change From Baseline in the 20-item Physician Withdrawal Checklist (PWC-20) Total Score(Baseline, Days 15, 21, and 28)
Number of Participants Achieving HAM-D Remission(Days 3，8，15, 21, and 28)
Number of Participants With Clinically Significant Abnormalities in Laboratory Measures in Treatment and FU Periods.(Treatment period: Up to Day 14; FU period: Day 15 to 42)
Number of Participants With Suicidal Ideation or Behavior Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) in Double-blind Treatment Period(Up to Day 14; FU period: Day 15 to 42)
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A)(Baseline, Days 15，28)
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score(Baseline, Days 3, 8, 15，21,28)