A Study of BRII-297 in Healthy Adult Subjects

NCT05845840 | Completed Phase 1

• 1 other identifier: BRII-297-001
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics of BRII-297 in healthy adult subjects. The main aim of the study is to evaluate the safety and tolerability after single dose intramuscular administration of BRII-297. The study also aims at characterizing the PK profiles of BRII-297 and brexanolone after single dose intramuscular administration. Participants will be enrolled in 6 cohorts (3 planned and 3 optional) with 6 participants per cohort \[(4 active: 2 placebo) - Cohorts 1 \& 2\] and 10 participants per cohort \[(8 active: 2 placebo) - Cohorts 3 to 6\]. Randomization for each cohort will be a two-step process. Sentinel subjects for each cohort will include 2 female subjects randomized 1:1 to BRII-297 or placebo who will be observed for at least 24 hours to ensure no significant safety events before administering study drug to the remaining non-sentinel subjects. The estimated total duration for each subject is up to 43 days, including screening period (28 days), dosing period (1 day), and post-dose follow-up period (14 days). IM injections will be administered in the gluteal muscle. Each participant in all cohorts will begin their inpatient stay at the clinical investigational site on Day -1 and remain as an inpatient at the site for sample collection and assessments for 15 days post dose (Day 15). Participants will be released at the end of the inpatient period.

Conditions

Postpartum Depression

Outcome Measures

Primary Outcomes (13)

• Number of participants with adverse events receiving BRII-297 compared to placebo

  To assess the safety and tolerability of a single infusion of BRII-297 as assessed by frequency of drug related adverse events, graded by severity.

  Time Frame: Day 0 - Day 15

• Number of participants with abnormal clinical vital signs

  Vital signs include pulse rate, blood pressure, respiratory rate and tympanic temperature

  Time Frame: Day 0 - Day 15

• Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) readings

  Time Frame: Day 0 - Day 15

• Number of participants with abnormal clinically significant clinical laboratory results

  Clinical laboratory tests include hematology, clinical chemistry, and liver function tests.

  Time Frame: Day 0 - Day 15

• Number of participants with abnormal S-STS - Sheehan Suicidality Tracking Scale (self-report) results

  Each question is rated from 0 to 4, with the highest score the worse outcome.

  Time Frame: Day 1 - Day 15

• Number of participants with abnormal SSS - Stanford Sleepiness Scale (self-report) results

  The SSS (self-report) is a subjective measure of sleepiness, The minimum value is 1 (active) and the maximum value is 7 (nearly asleep).

  Time Frame: Day 1 - Day 15

• PK of BRII-279 and brexanolone: Maximum observed plasma drug concentration Cmax

  The Cmax PK parameter calculated based on the observed plasma drug concentration versus time curve

  Time Frame: Day 0 - Day 15

• PK of BRII-279 and brexanolone: Time to maximum observed plasma drug concentration (Tmax)

  The PK parameter calculated will be Time to maximum observed plasma drug concentration (Tmax).

  Time Frame: Day 0 - Day 15

• PK of BRII-279 and brexanolone: Area under the curve from time 0 to last measurable concentration (AUClast)

  The PK parameters calculated will be Area under the plasma drug concentration-time curve from time 0 to last measurable concentration (AUClast).

  Time Frame: Day 0 - Day 15

• PK of BRII-279 and brexanolone: Area under the curve from time 0 to infinity (AUC0-inf)

  The PK parameters calculated will be Area under the curve from time 0 to infinity (AUC0-inf).

  Time Frame: Day 0 - Day 15

• PK of BRII-279 and brexanolone: Terminal elimination half-life (T ½)

  The PK parameter of Terminal elimination half-life (T ½) is calculated based on the plasma drug concentration-time curve

  Time Frame: Day 0 - Day 15

• PK of BRII-279 and brexanolone: Apparent clearance after extravascular administration (CL/F)

  Time Frame: Day 0 - Day 15

• PK of BRII-279 and brexanolone: Apparent volume of distribution (Vz/F)

  Time Frame: Day 0 - Day 15

Study Arms (2)

BRII-297

EXPERIMENTAL

Participants will receive a BRII-297 by Intramuscular injection

Drug: BRII-297

Placebo

PLACEBO COMPARATOR

Participants will receive placebo by Intramuscular injection

Drug: Placebo

Interventions

BRII-297 DRUG

Escalating doses of BRII-297 will be given in different cohorts i.e., Cohorts 1 through 6

Also known as: Escalating doses of BRII-297

BRII-297

Placebo DRUG

Escalating doses of placebo will be given in different cohorts i.e., Cohorts 1 through 6

Also known as: Placebo to match

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be 18 to 50 years inclusive, at the time of signing informed consent.
• Capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the informed consent and in the protocol in the opinion of the investigator.
• Subjects who are healthy as determined by medical evaluation including medical history, physical examination, cardiac monitoring using 12-lead ECG, and laboratory tests in the opinion of the investigator.
• Female or male
• a. Female subjects i. A female subject is eligible to participate if
• of non-childbearing potential defined as premenarchal, or premenopausal with documented (subject's self-report) bilateral tubal ligation or occlusion, bilateral oophorectomy, bilateral salpingectomy, or hysterectomy; or
• postmenopausal, documented as 12 months of spontaneous amenorrhea prior to Day 1, and in questionable cases, a blood sample at screening with simultaneous follicle stimulating hormone (FSH) consistent with postmenopausal status (refer to laboratory reference ranges for confirmatory levels); or
• of childbearing potential, not pregnant, not lactating and agrees to use one of the following acceptable methods of contraception until 30 days after the last dose of study drug:
• total abstinence from sexual activities, or
• double barrier method, or
• an intrauterine device or system, or
• established use of hormonal contraceptives including oral, implantable, injectable or transdermal contraceptives.
• b. Male subjects i. Male subjects with female partners of childbearing potential must comply withthe following contraception requirements from the time of study drug until90 days after the last dose of study drug administration.
• total abstinence, or
• vasectomy with documentation (subject's self-report) of azoospermia 90 days prior to Day 1 (without reversal surgery), or

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, infectious, cardiovascular, gastrointestinal, neoplastic (except for basal or squamous cell cancer), neurological, or psychiatric disorder (as determined by the Investigator) capable of significantly altering the absorption of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of the data.
• Any major surgical procedure or hospitalization within 6 months prior to Day -1 or during the study, unless deemed not clinically significant by the Investigator.
• A history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator.
• History or presence of an abnormal ECG which, in the Investigator's opinion, is clinically significant. A QTc interval duration Fridericia greater than 450 ms obtained as an average from triplicate screening ECGs after at least 10 minutes rest at screening.
• Systolic blood pressure greater than 140 mmHg or a diastolic blood pressure of greater than 90 mmHg after approximately 10 minutes rest at screening.
• Calculated glomerular filtration rate of less than 60 mL/min/1.73m2 by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology.
• History of alcohol or other substance disorders within 1 year prior to screening, or recent use of drugs of abuse or a positive urine screen for drugs of abuse at screening in the opinion of the Investigator.
• History of depression or suicidal thoughts and/or behaviors within 1-year prior to screening in the opinion of the Investigator and assessed by S-STS at screening.
• Has an average weekly alcohol intake that exceeds 10 units per week within 30 days prior to screening. One unit: 1 glass of wine 5 oz or 150 mL; 12 oz or 360 mL of beer; 1.5 oz or 45 mL of distilled spirits.
• Are unwilling to stop alcohol consumption within 72 hours prior to Day -1 (as confirmed by alcohol breath screen test) and for the duration of the study.
• Use any tobacco- or nicotine-containing products including, but not limited to cigarettes, electronic cigarettes (of any kind), pipes, vapes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to screen, Day -1 (as confirmed by cotinine testing), and during the study.
• Positive drug testing at screening and/or at Day -1. Subjects should refrain from eating poppy seed-containing food (e.g., poppy cake) at least 3 days before admission as this can falsify the urine drug screen.
• History of intolerance to IM injection.
• Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study.
• Donated more than 500 mL of blood within 90 days before study drug administration.

Sponsors & Collaborators

• Brii Biosciences Limited: lead

Study Sites (1)

CMAX

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Depression, Postpartum

Condition Hierarchy (Ancestors)

Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Natasha Demi Martin

  CMAX

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: May 6, 2023
• Study Start: May 15, 2023
• Primary Completion: November 21, 2023
• Study Completion: January 17, 2024
• Last Updated: January 18, 2024

Record last verified: 2023-08

Locations

AU (1)