Ignite Creation Date:
2024-05-06 @ 4:13 PM
Last Modification Date:
2024-10-26 @ 2:06 PM
Study NCT ID:
NCT04915300
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-04-18
First Post:
2021-05-19
Brief Title:
Apabetalone for Pulmonary Arterial Hypertension
Sponsor:
Laval University
Organization:
Laval University
Study Overview
Official Title:
Apabetalone for Pulmonary Arterial Hypertension a Phase 2 Clinical Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
APPROACH-2
Brief Summary:
Throughout the past twenty years numerous specific pharmacologic agents targeting the endothelial dysfunction associated with PAH have emerged Short term placebo-controlled randomized trials assessing PAH-specific monotherapy with these molecules have reported improvements in pulmonary hemodynamics and exercise capacity A recent meta-analysis also documented a reduction in short-term mortality of about 40 with such therapies Several randomized clinical trials evaluating PAH-specific combination therapy have been conducted Our recent meta-analysis showed that combination therapy was associated with a 35 risk reduction for the occurrence of clinical worsening compared to monotherapy Nonetheless the investigators also showed 17 of PAH patients receiving combination therapy still experienced clinical worsening over a median exposure of 16 weeks Moreover long-term survival on PAH-specific also therapy remains poor in the modern era with a yearly mortality rate of 15 in incident idiopathic PAH The identification of innovative therapeutic targets and validation of these complementary therapeutic interventions are thus urgently needed in PAH
The investigators and others K Stenmark University of Colorado and H Bogaard VU University Medical Center Amsterdam personal communications have published strong evidence that BRD4 plays a key role in the pathological phenotype in PAH accounting for disease progression and showed that BRD4 inhibition can reverse PAH in several animal models Intriguingly coronary artery disease CAD and metabolic syndrome are more prevalent in PAH compared with the global population suggesting a link between these diseases Interestingly BRD4 is also a trigger for calcification and remodeling processes and regulates transcription of lipoprotein and inflammatory factors all of which are important in PAH and CAD Apabetalone an orally available BRD4 inhibitor is now in a clinical development stage with a good safety profile
The overall objective of the study is to explore the efficacy and safety of apabetalone as an add-on therapy for adult PAH patients and to inform the conduct and the design of a Phase 3 trial
The primary objective of the study is to assess the efficacy of apabetalone as evaluated by the change in PVR over a period of 24 weeks compared to placebo in adult subjects with PAH on stable background therapy
Secondary objectives include changes at week 24 in 6MWD plasma NT-proBNP concentration WHO functional class ESCERS risk stratification score health-related quality of life and additional hemodynamic data from right heart
Exploratory objectives are to evaluate the effects of apabetalone compared to placebo in adult subjects with PAH on mortality and clinically relevant morbidity events and on circulating levels and transcription changes in whole blood markers of metabolism vascular calcification inflammation DNA damage and leucocyte expression of BMPR2
The investigators and others K Stenmark University of Colorado and H Bogaard VU University Medical Center Amsterdam personal communications have published strong evidence that BRD4 plays a key role in the pathological phenotype in PAH accounting for disease progression and showed that BRD4 inhibition can reverse PAH in several animal models Intriguingly coronary artery disease CAD and metabolic syndrome are more prevalent in PAH compared with the global population suggesting a link between these diseases Interestingly BRD4 is also a trigger for calcification and remodeling processes and regulates transcription of lipoprotein and inflammatory factors all of which are important in PAH and CAD Apabetalone an orally available BRD4 inhibitor is now in a clinical development stage with a good safety profile
The overall objective of the study is to explore the efficacy and safety of apabetalone as an add-on therapy for adult PAH patients and to inform the conduct and the design of a Phase 3 trial
The primary objective of the study is to assess the efficacy of apabetalone as evaluated by the change in PVR over a period of 24 weeks compared to placebo in adult subjects with PAH on stable background therapy
Secondary objectives include changes at week 24 in 6MWD plasma NT-proBNP concentration WHO functional class ESCERS risk stratification score health-related quality of life and additional hemodynamic data from right heart
Exploratory objectives are to evaluate the effects of apabetalone compared to placebo in adult subjects with PAH on mortality and clinically relevant morbidity events and on circulating levels and transcription changes in whole blood markers of metabolism vascular calcification inflammation DNA damage and leucocyte expression of BMPR2
Detailed Description:
This is a standard-design double-blind parallel-group placebo-controlled trial
Overall 72 well-characterized PAH patients 36 subjects in each treatment group apabetalone 100 mg BID or matching placebo that have been stable for 4 months on standard PAH-therapies as per guidelines Galie Humbert et al 2015 will be recruited in 8-15 participating centres site selection currently ongoing The participating centres will be recruited if they have the same approach to PAH patients in terms of choice and timing of treatments and have expertise in performing trials in PAH The initial Health Canada approval will be obtained Apabetalone will be provided by Resverlogix Corp Canada but Resverlogix had no input into the trial design and will not be involved in the conduct of the trial analysis interpretation of the results or the final manuscript
A 4-week pre-treatment phase will allow ensuring that patients are on stable doses of PAH medication Patients will be given apabetalone 100mg BID or placebo
Patients will be regularly followed to assess whether side effects At baseline and week 24 a cardiac catheterization will assess changes in pulmonary hemodynamics and RV function
An end-of-study visit is planned at week 28
Overall 72 well-characterized PAH patients 36 subjects in each treatment group apabetalone 100 mg BID or matching placebo that have been stable for 4 months on standard PAH-therapies as per guidelines Galie Humbert et al 2015 will be recruited in 8-15 participating centres site selection currently ongoing The participating centres will be recruited if they have the same approach to PAH patients in terms of choice and timing of treatments and have expertise in performing trials in PAH The initial Health Canada approval will be obtained Apabetalone will be provided by Resverlogix Corp Canada but Resverlogix had no input into the trial design and will not be involved in the conduct of the trial analysis interpretation of the results or the final manuscript
A 4-week pre-treatment phase will allow ensuring that patients are on stable doses of PAH medication Patients will be given apabetalone 100mg BID or placebo
Patients will be regularly followed to assess whether side effects At baseline and week 24 a cardiac catheterization will assess changes in pulmonary hemodynamics and RV function
An end-of-study visit is planned at week 28
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None