The overall objective of CARDIMMUN is to take PC-mAb to a commercially viable stage, with demonstrated proof of activity in patients and with the documentation needed to enter a clinical phase IIa (Proof-of-Concept) trial. To reach this objective, we must:
- Demonstrate efficacy of PC-mAb in preclinical disease models in a way that allow translation from preclinical models to secondary prevention in CVD patients
- Demonstrate good safety profile of PC-mAb in preclinical toxicity studies
- Demonstrate good safety and acceptable pharmacokinetic profiles (supporting once monthly dosing) of PC-mAb in phase I clinical studies
- Generate proof of activity data in patients
The 5 work packages will embrace concept testing in preclinical models using biomarkers applicable also in human disease, coronary flow reserve and glucose uptake in inflamed arteries, as well as required toxicity studies. Additionally, studies in man are planned that explores safety, pharmacokinetics, pharmacodynamics and indices of clinical efficacy.
The objectives of this work package is to strengthen the efficacy and safety profile of PC- mAb and to support the planned clinical studies. Disease models will be used that reflect the CVD indications in focus – severe Peripheral Arterial Disease (PAD) – and the read-outs will to a large extent be the same as in the planned clinical studies with PC-mAb. Moreover, specific preclinical studies will be done to explore potential new inflammatory and tissue damage biomarkers which could be used in clinical studies with PC-mAb. The safety profile of PC-mAb will be investigated in the required GLP toxicity studies.
The objectives for Clinical development is to run two Phase I studies with PC-mAb. The First in Human study was completed in 2015. This is a single ascending dose study in 48 healthy volunteers. CMC and Phase I enabling toxicology studies in two species were completed in 2014. A Phase IIa-enabling toxicology study in one species was completed in 2016. A second Phase I study in severe PAD patients receiving revascularisation interventions was completed in 2016. The second study confirms safety in patients, as well as secure appropriate design of a future Phase IIa POC study. The Phase I study in PAD patients includes exploratory pharmacodynamic end-points that have a potential to provide Proof-of-Activity data.
The main objective for Regulatory Management in the CARDIMMUN project is to draw up the clinical-regulatory strategy plan, present and consult with applicable regulatory authorities. Further, to develop and quality control all essential documents in such a plan.
The overall objective of the work package is to reach a business agreement for further clinical development, with a suitable industrial partner.
The main objective for Project management is to coordinate, administrate and disseminate activities in CARDIMMUN between work packages and responsible partners, administrate and report activities for the project to EU, facilitate communication between participating partners and disseminate information from CARDIMMUN to the general public and the scientific community.