Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001479897
Ethics application status
Approved
Date submitted
23/09/2021
Date registered
29/10/2021
Date last updated
18/08/2022
Date data sharing statement initially provided
29/10/2021
Date results information initially provided
18/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
An Open label, Single Ascending Dose Study of Intravenous and Oral Doses of BRN-002 to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Healthy Participants
Scientific title
A Phase 1, Open label, Single Ascending Dose Study of Intravenous and Oral Doses of BRN-002 to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects
Secondary ID [1] 305335 0
HV-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atherosclerosis 323654 0
Condition category
Condition code
Cardiovascular 321193 321193 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1A, open label, single ascending dose (SAD) study to evaluate the safety, PK (including oral bioavailability) and PD of intravenous (IV) and oral doses of BRN-002 in healthy subjects.
There will be 5 Cohorts of 6 healthy subjects. Each subject will receive a single IV dose of BRN-002. Cohort 2 will also receive a single equivalent oral dose of BRN-002 to evaluate oral bioavailability, one week after IV dosing. Subjects will be enrolled into Cohorts sequentially, with the exception of Cohort 1 & 2, that will be dosed simultaneously.
Investigational Product: BRN-002
Subjects will receive a single IV dose of 50, 250, 500, 1000 or 1500 mg/kg of BRN-002 administered as an infusion over 2 hours; subjects in Cohort 2 will also receive an equivalent oral dose of 250 mg/kg as an oral solution.
A Cohort Review Committee will evaluate the safety of each subject and the combined Cohorts prior to dose escalation in Cohorts 3, 4, and 5. Cohort 1 and Cohort 2 will be dosed
simultaneously.
The study duration will be up to 42 days for an individual subjects in Cohorts 1, 3, 4, and 5 and up to 60 days for an individual subject in cohort 2.
The treatment duration will be a single dose for Cohorts 1, 3, 4, and 5 and two single dose administrations for subjects in Cohort 2.
Intervention code [1] 321745 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328989 0
To evaluate the safety and tolerability of BRN-002 measured by the incidence, frequency, duration, and severity of Adverse Events.
This will include
Participant-reported adverse events and
Investigator-reported adverse events
Timepoint [1] 328989 0
Day 1 to end of the study.
Secondary outcome [1] 401031 0
To determine the PK profile of BRN-002
Parameters: Cmax, Tmax, AUC0-t, AUC0-inf, t1/2, CL, Vd, terminal elimination rate constant, oral bioavailability.
Timepoint [1] 401031 0
Blood samples for PK will be drawn pre-dose (<30 min), mid-infusion (±5 minutes), end of infusion (±5 minutes), 15 minutes (±5 minutes), 30 minutes (±5 minutes), 1 hour (± 5
minutes), 1.5 hour (±5 minutes), 2 hours (± 10 minutes), 3 hours (± 10 minutes), 4 hours (± 10 minutes), 5 hours (± 10 minutes), 6 hours (±10 minutes), 8 hours (±15 minutes),
and 24 hours (±30 minutes) post-infusion.
Secondary outcome [2] 401032 0
To evaluate the safety of BRN-002 by assessment of clinical laboratory test results, vital signs, ECGs, physical examinations, and audiologic evaluation
Timepoint [2] 401032 0
Vital signs, and clinical laboratory on D1, D2, and D3
ECG will be performed on Day 1 at baseline, mid infusion, end of infusion (EOI), 15 min, 30 min, 1 hour, 1.5 hours, 2, 3, 4 5, 6, and 8 hours post-infusion.
Audiologic evaluations at Day 3 and if needed, at Day28

Eligibility
Key inclusion criteria
1. Healthy subjects aged 18 to 65 years old, both inclusive
2. Normal audiogram at screening
3. Normal ECG at screening
4. Body mass index between 18.5 to 35
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Prior history of hearing abnormalities, inner ear disorders, frequent ear infections or
vestibular disturbance, i.e., Meniere’s disease,
2. Non-insulin or insulin-dependent diabetes mellitus (documented or on HbAc1 analysis
with HbA1C >6.5%)
3. Documented inflammatory disease (e.g., including but not limited to auto immune
disorder, chronic obstructive pulmonary disorder, inflammatory bowel disease, arthritis)
4. Known or diagnosed malignancies in the past 5 years
5. Infectious disease (documented or on lab analysis [hepatitis B and hepatitis C virus
[HBV/HCV], human immunodeficiency virus [HIV], Coronavirus disease 2019
[COVID-19])
6. Received a vaccination within 14 days prior to dosing
7. Acute illness within 30 days prior to dosing
8. Hospital admission or major surgery within 30 days prior to dosing
9. Use of prescription medications within 2 weeks/5 half-lives of dosing, whichever is
longer
10. Low-density lipoprotein cholesterol >130 mg/dL
11. Women who are pregnant, breast-feeding, or of child-bearing potential
12. History of cigarette smoking or nicotine vaping within the past year prior to screening
13. Vital sign parameters outside of the normal range

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/11/2021
Actual
8/11/2021
Date of last participant enrolment
Anticipated
1/02/2022
Actual
21/02/2022
Date of last data collection
Anticipated
Actual
11/05/2022
Sample size
Target
30
Accrual to date
Final
29
Recruitment outside Australia
Country [1] 24126 0
New Zealand
State/province [1] 24126 0
Auckland

Funding & Sponsors
Funding source category [1] 309696 0
Commercial sector/Industry
Name [1] 309696 0
Beren Therapeutics, PBC
Country [1] 309696 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Beren Therapeutics, PBC
Address
9200, Sunset Blvd, Ste 1010,
West Hollywood, CA 90069
Country
United States of America
Secondary sponsor category [1] 310722 0
None
Name [1] 310722 0
Address [1] 310722 0
Country [1] 310722 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309465 0
HDEC
Ethics committee address [1] 309465 0
Ministry of Health
Health and Disability Ethics Committee
P O Box 5013
Wellington 6140
Ethics committee country [1] 309465 0
New Zealand
Date submitted for ethics approval [1] 309465 0
14/09/2021
Approval date [1] 309465 0
14/10/2021
Ethics approval number [1] 309465 0

Summary
Brief summary
Beren Therapeutics is evaluating the therapeutic potential of BRN-002 when administered intravenously.
The purpose of this study is to evaluate the safety and tolerability of BRN-002, as well as to gain an understanding of the pharmacokinetics (PK), and oral bioavailability, of BRN-002 and how that correlates with potential pharmacodynamic (PD) changes.
There will be 5 cohorts of 6 healthy participants in the study. Each participant will receive a single IV dose of BRN-002 administered as an infusion. Cohort 2 will also receive a single equivalent oral dose of BRN-002 to evaluate oral bioavailability, one week after IV dosing. Participants will be enrolled into cohorts sequentially. A Cohort Review Committee will evaluate the safety of each participant and the combined cohorts prior to dose escalation.
Following screening, eligible participants will be admitted to the Phase 1 clinic on Day -1, receive a single IV infusion of BRN-002 on Day 1 and remain in the clinic until Day 3 then discharged approximately 48 hours post-dose after all scheduled PK and safety assessments have been collected. Eligible participants in Cohort 2 will be re-admitted to the Phase 1 clinic on Day 21 and receive an equivalent oral dose of BRN-002 on Day 22; the same PK and safety assessments will be collected and they will be discharged by the end of Day 24.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114250 0
Dr Paul Hamilton
Address 114250 0
New Zealand Clinical Research House
3 Ferncroft Street,
Grafton, Auckland
Postcode 1010.
Country 114250 0
New Zealand
Phone 114250 0
+64 7883437
Fax 114250 0
Email 114250 0
[email protected]
Contact person for public queries
Name 114251 0
Mr Scott Riccio
Address 114251 0
Trial Manager
Beren Therapeutics 9200 Sunset Blvd, Ste 1010, West Hollywood, CA 90069
Country 114251 0
United States of America
Phone 114251 0
+1 323 538 6434
Fax 114251 0
Email 114251 0
[email protected]
Contact person for scientific queries
Name 114252 0
Mr Scott Riccio
Address 114252 0
Trial Manager
Beren Therapeutics 9200 Sunset Blvd, Ste 1010, West Hollywood, CA 90069
Country 114252 0
United States of America
Phone 114252 0
+1 323 538 6434
Fax 114252 0
Email 114252 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.