None listed
Conditions
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.
Interventions
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 fo
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.
Sponsors
BakerIDI Heart and Diabetes Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
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.
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
Outcome results
None listed