Periodic Reporting for period 1 - CardioProtectMI (A new cardioprotective drug for acute treatment of myocardial infarction)
Período documentado: 2024-02-01 hasta 2025-01-31
Ischemic Heart Disease kills more than 1.7M people/year in the EU, the vast majority via a heart attack (Myocardial
Infarction - MI). Heart failure (HF) is the major cause of death after MI with a prevalence of >26M individuals globally.
While current treatment involving restoration of blood flow to the heart saves the MI patient´s life it also causes additional
damage to the heart through an inflammatory reaction (reperfusion injury).
ResoTher’s leading drug candidate, RTP-026, is an immunomodulating therapeutic aimed at resolving inflammation
triggered during MI, thereby reducing damage to the heart and significantly decreasing risk of HF and death. Pre-clinical
data suggests RTP-026 could reduce post-MI HF by >20%. A Phase I study has been conducted to determine safety and
tolerability of RTP-026 in Healthy Volunteers. With the EIC we aim to validate RTP-026 clinical effectiveness by means
of a Phase IIa patient proof of principle study and Phase IIb proof of concept study.
Infarction - MI). Heart failure (HF) is the major cause of death after MI with a prevalence of >26M individuals globally.
While current treatment involving restoration of blood flow to the heart saves the MI patient´s life it also causes additional
damage to the heart through an inflammatory reaction (reperfusion injury).
ResoTher’s leading drug candidate, RTP-026, is an immunomodulating therapeutic aimed at resolving inflammation
triggered during MI, thereby reducing damage to the heart and significantly decreasing risk of HF and death. Pre-clinical
data suggests RTP-026 could reduce post-MI HF by >20%. A Phase I study has been conducted to determine safety and
tolerability of RTP-026 in Healthy Volunteers. With the EIC we aim to validate RTP-026 clinical effectiveness by means
of a Phase IIa patient proof of principle study and Phase IIb proof of concept study.
In the course of the EIC project, significant strides have been made on the technical and scientific fronts, particularly in advancing RTP-026 to the clinical trial phase. Key milestones include:
Finalization and Approval of Clinical Trial Protocol:
The clinical trial protocol for the Phase IIa study was meticulously developed, aligning with regulatory standards and study objectives. Following rigorous internal and external review processes, the protocol was submitted and received official approval from relevant regulatory bodies, enabling the trial to proceed.
Completion of Site Initiation Visits:
Site initiation visits were conducted at participating clinical centers to ensure readiness and protocol adherence. These visits included comprehensive training sessions for the clinical teams on trial protocols, safety procedures, and data collection standards, setting a strong foundation for study execution.
Initiation of Phase IIa Study:
With all necessary approvals and site preparations completed, the Phase IIa clinical study was officially initiated. This marks a critical advancement in the project, as RTP-026 progresses from preclinical phases into early-stage clinical evaluation. This study will investigate the efficacy and safety of RTP-026 in myocardial infarction patients, aiming to establish proof-of-concept for its therapeutic potential.
These technical achievements represent important progress in the development of RTP-026 and form the foundation for further clinical and scientific validation in line with the EIC project’s objectives.
As the trial progressed, it became evident that the recruitment rate was slower than anticipated. To address this issue, continuous communication between ResoTher and clinical sites was maintained to understand the underlying causes of the delay.
To expand recruitment capacity, additional medical students were hired to cover evenings, nights and weekends. This measure has facilitated a broader recruitment window, improving patient accessibility and enrolment rates. Additionally, efforts have been made to streamline patient screening and consent procedures to minimize delays and optimize recruitment efficiency.
Recognizing the impact of patient selection criteria on recruitment, an amendment to the protocol was introduced to modify inclusion criteria, particularly concerning the Neutrophil-to-Lymphocyte Ratio (NLR). Analysis of data from 1,892 STEMI patients at Copenhagen University Hospital (Rigshospitalet) and Odense University Hospital between 2015 and 2016 demonstrated that higher NLR levels correlate with increased post-MI mortality. The study originally defined patients with NLR between 7 and 17 as high-risk for post-PCI mortality. However, further data analysis revealed that symptom-to-angiography times have significantly decreased since 2015/2016, influencing the relevance of the original NLR threshold. Given this shift, the NLR inclusion criterion was adjusted to a range of 4.8 to 17 to ensure that patients with a shorter duration of symptoms are appropriately classified. In cases of extremely short chest pain duration an elevated neutrophil count alone, regardless of lymphocyte levels, is now used as an indicator of high-risk patients. This amendment to the protocol was approved January 2025.
The implemented measures - expanding the recruitment window and amending the protocol to adjust the inclusion criteria - have significantly enhanced recruitment speed.
Finalization and Approval of Clinical Trial Protocol:
The clinical trial protocol for the Phase IIa study was meticulously developed, aligning with regulatory standards and study objectives. Following rigorous internal and external review processes, the protocol was submitted and received official approval from relevant regulatory bodies, enabling the trial to proceed.
Completion of Site Initiation Visits:
Site initiation visits were conducted at participating clinical centers to ensure readiness and protocol adherence. These visits included comprehensive training sessions for the clinical teams on trial protocols, safety procedures, and data collection standards, setting a strong foundation for study execution.
Initiation of Phase IIa Study:
With all necessary approvals and site preparations completed, the Phase IIa clinical study was officially initiated. This marks a critical advancement in the project, as RTP-026 progresses from preclinical phases into early-stage clinical evaluation. This study will investigate the efficacy and safety of RTP-026 in myocardial infarction patients, aiming to establish proof-of-concept for its therapeutic potential.
These technical achievements represent important progress in the development of RTP-026 and form the foundation for further clinical and scientific validation in line with the EIC project’s objectives.
As the trial progressed, it became evident that the recruitment rate was slower than anticipated. To address this issue, continuous communication between ResoTher and clinical sites was maintained to understand the underlying causes of the delay.
To expand recruitment capacity, additional medical students were hired to cover evenings, nights and weekends. This measure has facilitated a broader recruitment window, improving patient accessibility and enrolment rates. Additionally, efforts have been made to streamline patient screening and consent procedures to minimize delays and optimize recruitment efficiency.
Recognizing the impact of patient selection criteria on recruitment, an amendment to the protocol was introduced to modify inclusion criteria, particularly concerning the Neutrophil-to-Lymphocyte Ratio (NLR). Analysis of data from 1,892 STEMI patients at Copenhagen University Hospital (Rigshospitalet) and Odense University Hospital between 2015 and 2016 demonstrated that higher NLR levels correlate with increased post-MI mortality. The study originally defined patients with NLR between 7 and 17 as high-risk for post-PCI mortality. However, further data analysis revealed that symptom-to-angiography times have significantly decreased since 2015/2016, influencing the relevance of the original NLR threshold. Given this shift, the NLR inclusion criterion was adjusted to a range of 4.8 to 17 to ensure that patients with a shorter duration of symptoms are appropriately classified. In cases of extremely short chest pain duration an elevated neutrophil count alone, regardless of lymphocyte levels, is now used as an indicator of high-risk patients. This amendment to the protocol was approved January 2025.
The implemented measures - expanding the recruitment window and amending the protocol to adjust the inclusion criteria - have significantly enhanced recruitment speed.
Final infarct size is considered one of the best predictors of adverse long-term outcome for STEMI survivors. Indeed, there is a strong independent relationship between
infarct size measured one month after reperfusion and all-cause death, hospitalization for HF and the composite occurrence of
both within 1 year. Therefore, the introduction of a specific infarct-limiting therapy for MI has potential for both a massive impact
on patients´ future health as well as an enormous socio-economic benefit.
RTP-026 is expected significantly contribute to reducing the financial burden of
the healthcare system, associated to the adverse outcomes of STEMI (HF and death). Through a 20% reduction in
HF incidence, it can generate €456M in annual savings. RTP-026 is positioned to have significant benefits for
STEMI patients, as the first-in-class immunomodulator in the STEMI treatment
course, reducing the HF-associated mortality rate and comorbidities.
infarct size measured one month after reperfusion and all-cause death, hospitalization for HF and the composite occurrence of
both within 1 year. Therefore, the introduction of a specific infarct-limiting therapy for MI has potential for both a massive impact
on patients´ future health as well as an enormous socio-economic benefit.
RTP-026 is expected significantly contribute to reducing the financial burden of
the healthcare system, associated to the adverse outcomes of STEMI (HF and death). Through a 20% reduction in
HF incidence, it can generate €456M in annual savings. RTP-026 is positioned to have significant benefits for
STEMI patients, as the first-in-class immunomodulator in the STEMI treatment
course, reducing the HF-associated mortality rate and comorbidities.