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A Study of BRII-296 in Adults With Severe Postpartum Depression (PPD)

Primary Purpose

Severe Postpartum Depression

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

BRII-296

About this trial

This is an interventional treatment trial for Severe Postpartum Depression focused on measuring Treatment

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participant either must have ceased lactating at screening or is still lactating actively breastfeeding at screening , must agree temporarily cease giving breast milk to her infant(s) Participant has had a Major Depressive Episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Participant was <12 months postpartum Participant is amenable to intramuscular administration of investigational product on Day 1 and remaining inpatient until at least Day 4 Exclusion Criteria: Active psychosis Attempted suicide associated with current episode of postpartum depression Medical history of seizures Medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder

Sites / Locations

Clinical Research Center of FloridaRecruiting
South Florida Research Phase I-IV IncRecruiting
Cenexel ACMR Atlanta Center for Medical ResearchRecruiting
iResearch Atlanta, LLCRecruiting
Research Carolina EliteRecruiting
Maximos OB/GYNRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BRII-296 600 mg

Arm Description

Participants will receive BRII-296 600 milligram (mg) by intramuscular injection admixed with Depo Medrol (80 milligram per milliliter [mg/mL]) on Day 1.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of Participants With Adverse Events (AEs) According to Severity

Severity will be assessed according to the following scale: Mild, moderate and severe.

Number of Participants With Change From Baseline in Clinically Significant Vital Sign Parameters

Number of Participants With Abnormal Electrocardiogram (ECG) Parameters

Number of Participants With Change From Baseline in Clinically Significant Clinical Laboratory Evaluations

Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Responses

The suicidal ideation and behavior will be monitored during the study using the C-SSRS. This scale consists of a "Baseline/Screening" version that assesses the lifetime and recent experience of the participant with suicidal ideation and behavior, and a "Since Last Visit" version that focuses on suicidality since the last study visit. The C-SSRS includes "yes" or "no" responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe).

Change From Baseline in Glasgow Coma Scale (GCS) Score

The GCS is a simple measure of the depth and duration of impaired consciousness and coma. 3 domains of alertness will be evaluated: eye opening response (scored 1 [None] to 4 [Spontaneous]), verbal response (scored 1 [None] to 5 [Oriented]), and motor response (scored 1 [None] to 6 [Obeys commands]). Total scores range from 3 to 15, with 15 reflecting full alertness.

Change From Baseline in Stanford Sleepiness Scale (SSS) Score

The SSS is a participant-rated measure of sleepiness, frequently used for both research and clinical purposes. The SSS evaluates sleepiness at specific moments in time. Respondents rate their current degree of sleepiness and alertness on a scale of 1 to 7, where the lowest score of '1' indicates the respondent is 'feeling active, vital, alert, or wide awake' and the highest score of '7' indicates the respondent is 'no longer fighting sleep, sleep onset soon; having dream-like thoughts'.

PK of Brexanolone: Maximum Observed Plasma Concentration (Cmax)

PK of Brexanolone: Time to Reach Cmax (Tmax)

PK of Brexanolone: Area Under the Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last)

PK of Brexanolone: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf)

PK of Brexanolone: Apparent Terminal Elimination Half-life (t½)

PK of Brexanolone: Apparent Clearance (CL/F)

PK of Brexanolone: Volume of Distribution (Vz/F)

Secondary Outcome Measures

Change From Baseline in Hamilton Depression Rating Scale (HAM-D) Total Score

The 17-item HAM-D will be used to rate the severity of depression in participants who are already diagnosed as depressed. The 17-item HAM-D is comprised of individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, and worthless), feelings of guilt, suicide, insomnia (early, middle, and late), work and activities, retardation (slowness of thought and speech, impaired ability to concentrate, and decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The total scores range from 0-52. Higher score indicates more depression.

Number of Participants With HAM-D Response

Response is defined as >=50 percent (%) reduction from baseline in HAM-D total score. The HAM-D is a 17-item scale used to rate the severity of depression in participants who are already diagnosed as depressed. The total scores of HAM-D range from 0-52. Higher score indicates more depression.

Number of Participants With HAM-D Remission

Remission is defined as <=7.0 HAM-D total score. The HAM-D is a 17-item scale used to rate the severity of depression in participants who are already diagnosed as depressed. The total scores of HAM-D range from 0-52. Higher score indicates more depression.

Number of Participants With Clinical Global Impression - Improvement (CGI-I) Response

The CGI-I item employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The clinician will rate the participant's total improvement, whether or not it is due entirely to investigational product treatment. Response choices include: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. CGI-I response will be defined as having a CGI-I score of "very much improved" or "much improved."

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Response

The CGI-S item uses a 7- point Likert scale to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating. Choices include: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill.

Change From Baseline in HAM-D Bech-6 Subscale Score

The HAM-D Bech 6 subscale score is calculated as the sum of the following six items: Item # 1 (depressed mood), Item # 2 (feelings of guilt), Item # 7 (work and activities), Item # 8 (retardation), Item # 10 (anxiety psychic), and Item # 13 (general somatic symptoms). Each item is scored in a range of 0 to 2 or 0 to 4, with higher scores indicating a greater degree of depression. The scores will be transformed to a 100-point scale with a higher score indicating a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Change From Baseline in HAM-D Individual Item Score

The HAM-D comprises individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score

The 14-item HAM-A will be used to rate the severity of symptoms of anxiety. Each of the 14 items is defined by a series of symptoms and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scoring for the HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56, where less than (<) 17 indicates mild severity, 18 to 24 mild to moderate severity, and 25 to 30 moderate to severe severity. The HAM-A total score will be calculated as the sum of the 14 individual item scores.

Full Information

NCT ID

NCT06057012

First Posted

September 21, 2023

Last Updated

October 20, 2023

Sponsor

Brii Biosciences Limited

1. Study Identification

Unique Protocol Identification Number

NCT06057012

Brief Title

A Study of BRII-296 in Adults With Severe Postpartum Depression (PPD)

Official Title

A Phase 2a, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Descriptive Efficacy of BRII-296 in Adults With Severe Postpartum Depression (PPD)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 29, 2023 (Actual)

Primary Completion Date

June 26, 2024 (Anticipated)

Study Completion Date

June 26, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Brii Biosciences Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of BRII-296 administered by 2 intramuscular injections, administered with Depo Medrol as assessed by the incidence of adverse events, changes from baseline in vital signs, pulse oximetry, clinical laboratory evaluations, electrocardiograms (ECGs), Stanford Sleepiness Scale (SSS), Glasgow Coma Scale (GCS) in conjunction with clinical assessment, and suicidal ideation using the Columbia Suicide Severity Rating Scale (C-SSRS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Postpartum Depression

Keywords

Treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

BRII-296 600 mg

Arm Type

Experimental

Arm Description

Participants will receive BRII-296 600 milligram (mg) by intramuscular injection admixed with Depo Medrol (80 milligram per milliliter [mg/mL]) on Day 1.

Intervention Type

Drug

Intervention Name(s)

BRII-296

Intervention Description

2 intramuscular injections 300 mg each of BRII-296 admixed with Depo Medrol 40 mg/mL per injection, will be administered in participants with PPD.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time Frame

From the first dose of study drug up to Day 45

Title

Number of Participants With Adverse Events (AEs) According to Severity

Description

Severity will be assessed according to the following scale: Mild, moderate and severe.

Time Frame

From the first dose of study drug up to Day 45

Title

Number of Participants With Change From Baseline in Clinically Significant Vital Sign Parameters

Time Frame

Baseline up to Day 45

Title

Number of Participants With Abnormal Electrocardiogram (ECG) Parameters

Time Frame

From the first dose of study drug up to Day 45

Title

Number of Participants With Change From Baseline in Clinically Significant Clinical Laboratory Evaluations

Time Frame

From the first dose of study drug up to Day 45

Title

Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Responses

Description

Time Frame

Baseline up to Day 45

Title

Change From Baseline in Glasgow Coma Scale (GCS) Score

Description

Time Frame

Baseline up to Day 45

Title

Change From Baseline in Stanford Sleepiness Scale (SSS) Score

Description

Time Frame

Baseline up to Day 45

Title

PK of Brexanolone: Maximum Observed Plasma Concentration (Cmax)

Time Frame

Day 1- Day 45

Title

PK of Brexanolone: Time to Reach Cmax (Tmax)

Time Frame

Day 1- Day 45

Title

PK of Brexanolone: Area Under the Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last)

Time Frame

Day 1- Day 45

Title

PK of Brexanolone: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf)

Time Frame

Day 1- Day 45

Title

PK of Brexanolone: Apparent Terminal Elimination Half-life (t½)

Time Frame

Day 1- Day 45

Title

PK of Brexanolone: Apparent Clearance (CL/F)

Time Frame

Day 1- Day 45

Title

PK of Brexanolone: Volume of Distribution (Vz/F)

Time Frame

Day 1- Day 45

Secondary Outcome Measure Information:

Title

Change From Baseline in Hamilton Depression Rating Scale (HAM-D) Total Score

Description

Time Frame