Clinical trial NCT05938179: A Study of HS-10353 in Adult Participants With Major Depressive Disorder
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study Evaluating the Efficacy and Safety of HS-10353 in Chinese Adults With Depression.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder (MDD)
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-10
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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;
* 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;
* Abnormal 12-lead ECG was clinically significant at screening/baseline: QT interval (QTcF) corrected by Fridericia formula had an absolute value of QTcF \>450 ms for males and \>470 ms for females; If QTcF is prolonged in the first measurement, the average value of 3 consecutive ECGs (10 minutes between each measurement) should be taken to confirm;
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 times upper limit of normal (ULN), serum creatinine (Cr) \> 1.5 times ULN;
* Patients with diseases that may have clinical significance (such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal musculoskeletal system, metabolism, endocrine system, skin diseases, blood system diseases, immune diseases and tumors, etc.) are assessed by the researcher as not suitable for participation in this study;
* Any other conditions assessed by the investigator that might interfere with compliance, harm the health of the subject, or interfere with the study outcome.

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