Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001377729
Ethics application status
Approved
Date submitted
18/10/2022
Date registered
26/10/2022
Date last updated
20/03/2023
Date data sharing statement initially provided
26/10/2022
Date results information initially provided
20/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and Activity of Oral HPBCD in Coronary Artery Disease
Scientific title
A Single-group Treatment, Phase 2a, Open-label, Single-arm Study to Assess the Safety, Tolerability, and Pharmacodynamic Effect of Oral HPBCD in Adult Participants with Coronary Artery Disease
Secondary ID [1] 308122 0
BRN-002-02-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease 327830 0
Condition category
Condition code
Cardiovascular 324905 324905 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will receive 250 mg/kg oral dose of HPBCD daily for 14 days. The active ingredient of HPBCD is 2-hydroxypropyl-ß-cyclodextrin (HPBCD). Patient will take HPBCD as an oral solution. HPBCD will be administered to patients by site staff and adherence will be assessed through source data where record of the quantity of HPBCD dispensed to and administered by each participant must be maintained and reconciled with study drug administration and compliance records
Intervention code [1] 324579 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332754 0
To evaluate the safety and tolerability of multiple oral doses of HPBCD. This will be assessed through incidences and severity of treatment emergent adverse events (TEAEs), which are defined as adverse events (AEs) with a date of onset after the first dose of study drug and/or AEs that worsen after the onset of administrations. TEAEs will be self-reported by participants
Timepoint [1] 332754 0
Assessment occurs daily from Day 1 (first dose) through Day 15 (end of study visit)
Secondary outcome [1] 414604 0
To evaluate the effect of multiple oral doses of HPBCD on apolipoprotein A1 (ApoA1) via blood sample analysis
Timepoint [1] 414604 0
Secondary outcome will be measured from day 1 (first dose) through day 15 (end of study) though blood samples taken during clinic visits on days 1, 2, 8, 14 and 15.

Eligibility
Key inclusion criteria
1. Participant must be 18 to 75 years of age (inclusive) at the time of signing the informed
consent form (ICF).
2. Has a documented history of stable (>3 months prior to screening) coronary heart disease (at least 1 of the following):
-Acute coronary syndrome or myocardial infarction.
-Coronary revascularization procedure.
-Diagnosis of coronary heart disease based on anatomic or functional test results.
3. Any antihypertensives, glucose- or lipid-lowering medications, or hormone therapies must have been taken as a stable dose for at least 4 weeks prior to screening.
4. Body mass index within the range of 18.5 to 35 kg/m2 (inclusive) and body weight less than or equal to 140kg.
5. Male participants are eligible if they agree to all of the following requirements during the study intervention period and for at least 30 days after the last dose of study drug:
-Refrain from donating sperm; AND
-Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) or agree to utilize highly effective contraception
6. Female participants are eligible if they meet all of the following requirements during the study intervention period and for at least 30 days after the last dose of study drug:
-Refrain from donating eggs (ova, oocytes) for the purpose of reproduction.
-Meet at least one of the following criteria:
+Is not a woman of childbearing potential (WOCBP); OR
+Is a WOCBP, has a negative serum pregnancy test within 24 hours before the first dose of study drug, and agrees to utilize highly effective contraception.
7. Is capable of understanding the ICF, has provided signed and witnessed informed consent, and agreed to comply with the protocol requirements.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of any significant cardiac event or procedure within 3 months prior to Screening, including:
-Acute coronary syndrome or myocardial infarction
-Coronary revascularization procedure
-Clinically significant electrocardiogram (ECG) abnormalities, including but not limited to conduction abnormalities or atrial fibrillation
2. Insulin-dependent diabetes mellitus Type 1 or Type 2, or hemoglobin A1c lower than or equal to 9.5%
3. Systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 100 mmHg despite antihypertensive medication
4. Donation or loss of blood greater than or equal to 450 mL within 8 weeks prior to screening
5. Clinically significant laboratory abnormalities, including:
-Aspartate transaminase (AST) or alanine transaminase (ALT) > 3 × upper limit of normal (ULN)
-Total bilirubin > 1.5 × ULN
-Fasting serum triglycerides greater than or equal to 500 mg/dL
-LDL cholesterol lower than or equal to 40 mg/dL
-HDL cholesterol > 80 mg/dL
-Hemoglobin < 11.0 g/dL
-Platelet count < 150,000/µL
-Thyroid-stimulating hormone (TSH) > 1.5 × ULN
6. Any physical or psychiatric condition which at the Investigator’s discretion may put the
participant at risk, may confound the trial results, or may interfere with participation in
this clinical trial.
7. The participant is pregnant or breastfeeding.
8. History of any malignancy (other than basal cell carcinoma of the skin or in situ cervical
cancer) within the past 5 years.
9. Cognitive, psychological, or addictive conditions (including alcoholism or drug/ chemical abuse) that, in the opinion of the Investigator, may interfere with participant compliance,put the participant at risk, or preclude informed consent.
10. Current use of bile acid sequestrants or cholesterol absorption inhibitors (for example, ezetimibe).
11. Current enrollment or past participation in another investigational study in which an investigational intervention (for example, drug, vaccine, and invasive device) was administered within 30 days or 5 half-lives, whichever is longer, of screening in this clinical study.
12. Positive blood screen for hepatitis B surface antigen or core antibody, hepatitis C antibody, or human immunodeficiency virus 1 or 2 antibodies.
13. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins (thyroid replacement therapy can be included if on stable dose for at least 12 weeks prior to screening and TSH level is within normal limits).
14. Planned surgery or coronary angiography/intervention during the time of study participation; any major surgery within 6 weeks of screening, or surgical or medical condition which might jeopardize participant’s safety.
15. Sensitivity to the study drug, or components thereof, or drug or other allergy that, in the opinion of the Investigator or medical monitor, contraindicates participation in the study.

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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/12/2022
Actual
7/12/2022
Date of last participant enrolment
Anticipated
31/01/2023
Actual
7/02/2023
Date of last data collection
Anticipated
15/03/2023
Actual
22/02/2023
Sample size
Target
10
Accrual to date
Final
10
Recruitment outside Australia
Country [1] 25051 0
New Zealand
State/province [1] 25051 0

Funding & Sponsors
Funding source category [1] 312378 0
Commercial sector/Industry
Name [1] 312378 0
Beren Therapeutics P.B.C
Country [1] 312378 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
PPD part of Thermo Fisher
Address
Office 141-151 Westhaven Drive, Auckland, 1011
Country
New Zealand
Secondary sponsor category [1] 313944 0
None
Name [1] 313944 0
Address [1] 313944 0
Country [1] 313944 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311736 0
HDEC Northern A
Ethics committee address [1] 311736 0
Ministry of Health Health and Disability Ethics Committees, PO Box 5013, Wellington 6140
Ethics committee country [1] 311736 0
New Zealand
Date submitted for ethics approval [1] 311736 0
05/10/2022
Approval date [1] 311736 0
18/11/2022
Ethics approval number [1] 311736 0
2022 FULL 13229

Summary
Brief summary
Repeat-dosing of HPBCD is expected to result in increased levels of ApoA1, and the subsequent formation of high-density lipoprotein (HDL) particles in patients.
This is a multi-centre, Phase 2a study. It is a single-arm, open label study in patients with coronary artery disease. Patients will receive a daily oral dose of HPBCD at 250mg/kg for 14 days. The study aims to evaluate the safety and tolerability of single and multiple oral doses of HPBCD. The study will also evaluate the changes in levels of Apo1 after a single and multiple oral doses of HPBCD over the duration of the study
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122186 0
Prof Richard Stubbs
Address 122186 0
P3 Research
273 Broadway Ave, Palmerston North, 4414
Country 122186 0
New Zealand
Phone 122186 0
+64 6 241 8009
Fax 122186 0
Email 122186 0
RichardS@p3research.co.nz
Contact person for public queries
Name 122187 0
Prof Richard Stubbs
Address 122187 0
P3 Research
273 Broadway Ave, Palmerston North, 4414
Country 122187 0
New Zealand
Phone 122187 0
+64 6 241 8009
Fax 122187 0
Email 122187 0
RichardS@p3research.co.nz
Contact person for scientific queries
Name 122188 0
Ms Katelyn Diffin
Address 122188 0
Beren Therapeutics P.B.C
9200 W Sunset Blvd, Ste 1010,
West Hollywood, CA 90069
Country 122188 0
United States of America
Phone 122188 0
+1 973 919 3569
Fax 122188 0
Email 122188 0
KDiffin@berentx.com

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


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.