A Study of HS-10353 in Adult Participants With Major Depressive Disorder

NCT05938179 | Unknown Phase 2

• 1 other identifier: HS-10353-201
• Study Type: interventional
• Target: 144
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the 17-item HAM-D Total Score at 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.

  Baseline (BL), Day 15

Secondary Outcomes (13)

• 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

• Number of Participants Achieving HAM-D Remission

  Days 3，8，15, 21, and 28

• 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

Study Arms (2)

HS-10353 Capsules

EXPERIMENTAL

Drug: HS-10353 30mg oral capsules; Drug: HS-10353 50mg oral capsules

HS-10353 matched-placebo oral capsules

EXPERIMENTAL

Drug: Placebo for HS-10353 30mg capsules; Drug: Placebo for HS-10353 50mg capsules

Interventions

HS-10353 30mg oral capsules DRUG

HS-10353 30mg oral capsules

HS-10353 Capsules

HS-10353 50mg oral capsules DRUG

HS-10353 50mg oral capsules

HS-10353 Capsules

Placebo for HS-10353 30mg capsules DRUG

Placebo for HS-10353 30mg capsules

HS-10353 matched-placebo oral capsules

Placebo for HS-10353 50mg capsules DRUG

Placebo for HS-10353 50mg capsules

HS-10353 matched-placebo oral capsules

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Have participated in any clinical trial or taken any clinical trial drug within the last 1 year;
• Women in pregnancy, puerperal period, postpartum 6 months or breastfeeding period, who have planned pregnancy in the near future;
• Poor blood pressure control or abnormal heart rate: at rest, systolic blood pressure (SBP) ≥140 mmHg or \< 90 mmHg, diastolic blood pressure (DBP) ≥90 mmHg or \< 60 mmHg; Heart rate \>100 bpm or \<60bpm;
• The presence, in the investigator's judgment, of any surgical condition or condition that is likely to significantly affect drug absorption, distribution, metabolism, or excretion, or that is likely to pose a hazard to participants in the trial; Such as gastrointestinal surgery history (gastrectomy, gastrostomy, enterectomy, etc.), gastroenteritis, gastrointestinal ulcer, gastrointestinal bleeding history; Urinary tract obstruction or dysuria;
• Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis seroreaction (TRUST), human immunodeficiency virus (HIV) antibody test positive;

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Peng Zhou

CONTACT

18013002767; zhoup7@hspharm.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: July 10, 2023
• Study Start: August 31, 2023
• Primary Completion: November 1, 2024
• Study Completion: April 30, 2025
• Last Updated: July 11, 2023

Record last verified: 2023-07