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Trial registered on ANZCTR


Registration number
ACTRN12616000482460
Ethics application status
Approved
Date submitted
8/04/2016
Date registered
13/04/2016
Date last updated
13/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 2, randomised, double-blind, placebo-controlled, adaptive design study investigating the safety and effectiveness of orally administered BGP-15 on cardiac fibrosis and heart function in people with Non-Ischaemic Dilated Cardiomyopathy (NIDCM)
Scientific title
An Exploratory Phase 2 Study to Determine Safety, Tolerability and Impact of BGP-15 on cardiac fibrosis and ventricular remodelling in patients with Non-Ischaemic Dilated Cardiomyopathy (NIDCM)
Secondary ID [1] 288951 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-ischemic dilated cardiomyopathy 298317 0
Cardiac fibrosis 298318 0
Condition category
Condition code
Cardiovascular 298439 298439 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The first 30 participants will be randomised to receive a once daily oral administration of placebo, 200mg or 400 mg BGP-15. After exposure for 3 months, the DMC will assess safety and recommend a single daily oral dose (200mg or 400mg) of BGP-15. For the first 30 participants, if the recommended dose is 200mg BGP-15, all those on 400mg are reduced to 200mg daily doses for the remainder of the 12 months of treatment. The 200mg dose group and the placebo group stay on their respective doses for the remainder of the 12 months of therapy. If the recommended dose is 400 mg, all treatment groups remain the on the same dosage for the remainder of the 12 months of treatment. This results in the 200 mg dose group staying at this dosage for the entire 12 months of treatment. For Part B, the final 60 participants will receive either placebo or the recommended dose of BGP-15 for the entire 12 months of treatment. Adherence will be assessed by self reporting of the quantity of remaining capsules.
Intervention code [1] 294432 0
Treatment: Drugs
Comparator / control treatment
Placebo controlled
Control group
Placebo

Outcomes
Primary outcome [1] 297929 0
Safety and tolerability compared between placebo and drug treatment. Safety will be assessed by blood tests (FBE, LFT, UEC) and the total number and severity of adverse events as well as the number and severity of treatment related adverse events. Tolerability refers to the ability of the participant to tolerate the adverse events. Tolerability will assessed by analysis of dropout rates specifically due to adverse events. Given the small number of previous studies and adverse event profile has not yet emerged from the recorded incidences of AE’s and SAE’s. The side effects previously reported in studies with placebo and BGP-15 include mild to moderate increases in appetite and weight gain, headache, gastrointestinal symptoms including nausea and diarrhoea, fatigue or sleepiness. Less common side effects include mild changes to ECG rhythm and moderate increases in liver enzymes.
Timepoint [1] 297929 0
The end of 3, 6 and 12 months treatment
Secondary outcome [1] 322663 0
Extent of interstitial fibrosis, as measured by native myocardial T1 time on CMR, compared between placebo and drug treatment.
Timepoint [1] 322663 0
The end of 6 and 12 months of treatment
Secondary outcome [2] 322664 0
The post contrast T1 time as measured by CMR will be compared between the placebo and drug treatment groups
Timepoint [2] 322664 0
The end of 6 and 12 months of treatment
Secondary outcome [3] 322665 0
Placebo and drug treatment groups will be compared for changes in left ventricular end-diastolic index (LVEDVi) as evaluated by CMR and echocardiography quantification.
Timepoint [3] 322665 0
The end of 6 and 12 months of treatment
Secondary outcome [4] 322666 0
Diastolic function will be compared between placebo and drug treatment groups using echo-doppler indices E/e' and E/A ratio.
Timepoint [4] 322666 0
The end of 6 and 12 months of treatment
Secondary outcome [5] 322667 0
Exercise capacity will be assessed by VO2 max testing using a standard treadmill protocol. Change in VO2 max will be compared between placebo and drug treatment groups.
Timepoint [5] 322667 0
The end of 6 and 12 months of treatment
Secondary outcome [6] 322759 0
The estimated extracellular collagen volume (ECV) as measured by CMR will be compared between the placebo and drug treatment groups
Timepoint [6] 322759 0
The end of 6 and 12 months of treatment
Secondary outcome [7] 322760 0
Placebo and drug treatment groups will be compared for changes in LV end-systolic volume (LVESVi) as evaluated by CMR and echocradiography quantification.
Timepoint [7] 322760 0
The end of 6 and 12 months of treatment
Secondary outcome [8] 322761 0
Placebo and drug treatment groups will be compared for changes in Left ventricular ejection fraction (LVEF) as evaluated by CMR and echocardiography quantification.
Timepoint [8] 322761 0
After 6 and 12 month of treatment

Eligibility
Key inclusion criteria
1. Males aged 18-80 years, inclusive
2. Females aged 18-80 years inclusive meeting the following criteria:
- A negative serum pregnancy test at Screening, not breast feeding and did not plan to be pregnant during the study, AND if one of the following three criteria was met:
-They had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form;
-They had been postmenopausal for at least 1 year; or,
-They were of childbearing potential and practiced one of the following methods of birth control throughout the study: injectable or implantable hormonal contraception or intrauterine device; or two of the following methods of birth control throughout the study: oral or patch contraception plus a barrier contraceptive (e.g., diaphragm plus spermicide, male or female condom plus spermicide, or vasectomized male partner).
3. Known history of non-ischemic dilated cardiomyopathy as determined using appropriate invasive and/or non-invasive imaging assessments
4. Reduced left ventricular function, with a calculated LVEF between 35-50% based on CMR imaging
5. Evidence for significant LV dilation defined as > 2SD above the mean LVEDVi value for a gender compared normal population
6. Evidence of increased interstitial myocardial fibrosis, suggested by a native myocardial T1 time greater than 1218ms.
7. No evidence for maximum LV wall thickness > 15mm at end-diastole by cardiac magnetic resonance imaging or echocardiography
8. No evidence for resting LV outflow tract (LVOT) obstruction > 10mmHg at either valvular and/or sub-valvular level
9. Stable symptoms with no hospital admissions for heart failure in the preceding 3 months
10. Stable heart failure medical therapy with no changes in medications (other than diuretic dose) in preceding 3 months
11. Able to perform exercise testing but unable to achieve greater than the lower limit of normal VO2 max (20 mL/kg/min) at visit 2.
12. Expected life expectancy of at least 2 years.
13. Have given written informed consent
14. In the investigator’s opinion, the participant is able and willing to comply with study medication as required by the protocol.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any contraindication to CMR scanning (non-CMR compatible pacemaker, other metallo-prosthetic implant, or severe claustrophobia).
2. Stage IIIB or worse renal dysfunction (glomerular filtration rate [GFR] <45ml/hour)
3. Plan for cardiac pacemaker of implantable cardioverter defibrillator (ICD) insertion.
4. Any severe comorbidity precluding study drug or successful completion of study protocol.
5. Previous myocardial infarction
6. Evidence of liver disease defined as aspartate transaminase (AST), alanine transaminase (ALT) or total bilirubin >2 x upper limit of normal at Visit 2
7. History of active malignancy within the past 5 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma, or non-malignant melanoma
8. History or evidence of drug or alcohol abuse within the last 12 months of Visit 1
9. Use of other investigational drugs and devices at the time of enrolment, or within 90 days of Visit 1
10. History of non-compliance to medical regimens or unwillingness to comply with the study protocol
11. Any condition that in the opinion of the Investigators would confound the evaluation and interpretation of the data
12. Persons directly involved in the execution of the protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 293309 0
Commercial sector/Industry
Name [1] 293309 0
N-Gene Research Laboratories Australia Pty Ltd
Address [1] 293309 0
26 Gorge Road, Bellevue Heights, 5050, SA
Country [1] 293309 0
Australia
Primary sponsor type
Other
Name
BakerIDI Heart and Diabetes Institute
Address
75 Commercial Road Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 292120 0
None
Name [1] 292120 0
Address [1] 292120 0
Country [1] 292120 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294783 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 294783 0
Office of Ethics & Research Governance
Alfred Health
55 Commercial Road
Melbourne VIC 3004
Ethics committee country [1] 294783 0
Australia
Date submitted for ethics approval [1] 294783 0
25/02/2016
Approval date [1] 294783 0
01/04/2016
Ethics approval number [1] 294783 0

Summary
Brief summary
This study aims to examine the safety and effect of 12 months of BGP-15 treatment on heart function in people with non-ischemic dilated cardiomyopathy. This is a phase 2, randomised, double-blind, placebo-controlled, adaptive design study of orally administered BGP-15 in patients with evidence of increased cardiac fibrosis as suggested by cardiac MR imaging. Safety monitoring will be conducted at 3, 6 and 12 months of drug therapy. Efficacy will be assessed by cardiac MR, echocardiography and exercise capacity tests at baseline, 6 months and 12 months. The adaptive design study has 2 parts. Part A involves treatment of 30 participants with placebo and 2 doses of BGP-15. Safety analysis by an independent DMC will recommend an on-going dose for Part B (or termination if required). Part B involves 60 patients treated with placebo and one dose of BGP-15.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65022 0
A/Prof Andrew Taylor
Address 65022 0
BakerIDI Heart and Diabetes Institute
PO Box 6492
Melbourne, VIC, 3004
Country 65022 0
Australia
Phone 65022 0
+61 404007992
Fax 65022 0
Email 65022 0
andrew.taylor@bakeridi.edu.au
Contact person for public queries
Name 65023 0
Dr Tamara Allen
Address 65023 0
BakerIDI Heart and Diabetes Institute
PO Box 6492
Melbourne, VIC, 3004
Country 65023 0
Australia
Phone 65023 0
+61 385321709
Fax 65023 0
Email 65023 0
tamara.allen@bakeridi.edu.au
Contact person for scientific queries
Name 65024 0
A/Prof Andrew Taylor
Address 65024 0
BakerIDI Heart and Diabetes Institute
PO Box 6492
Melbourne, VIC, 3004
Country 65024 0
Australia
Phone 65024 0
+61 404007992
Fax 65024 0
Email 65024 0
andrew.taylor@bakeridi.edu.au

No information has been provided regarding IPD availability
Summary results
No Results