Exploratory drug development
The focus of the research of the Center for Clinical Pharmacology is on the exploratory phase of clinical drug development and includes small molecules as well as biologicals. Among others, following trials are performed:
- First-in-Man trials (FIM), including single and multiple ascending dose trials (SAD and MAD) comprise 25% of our research activities. Often these trials have an adaptive design which allows dose adaptations as data become available. The flexible nature of these trials is time and cost saving while the safety remains guaranteed.
- Imaging trials mainly involving Positron Emission Tomography (PET) and MRI, or both (PET-MRI), comprise another 25% of our research activities. Radioactive tracers, produced in the on-site GMP certified radiopharmacy, are administered to trial participants to evaluate CNS penetration and receptor occupancy. Imaging trials are an invaluable tool early in the development process of CNS compounds by guiding dose selections and go/no-go decisions. In support of imaging trials, radiotracers are developed and validated in microdosing trials involving an exploratory clinical trial approach.
The Molecular Imaging Center "MIRACLE" (Molecular Imaging Research and Clinic Leuven) is designed to integrate the highly sensitive techniques of PET, SPECT, microPET and microSPECT with other anatomo-functional imaging modalities such as CT, MRI and optical imaging to develop an integrated set of core technologies for drug development, clinical trials and fundamental research studies. The Core Lab incorporates the available know-how and infrastructure of the Division of Nuclear Medicine for study design, data mining and analysis of functional imaging-based clinical trials.
- In collaboration with key opinion leaders of the University Hospital, Proof-of-Concept trials (PoC) are performed in selected patient populations. These trials include a wide range of disease areas: cystic fibrosis, COPD, diabetes mellitus, rheumatoid arthritis, migraine, hypertension and, more recently, also oncology patients.
Areas of special interest
Over the years a special expertise has been acquired in the area of pain in general and migraine in particular.
Regarding migraine, many acute and chronic antimigraine drugs, small molecules as well as biologicals, were tested at our clinic and developed up to Proof-of-Principle (PoP). In the context of these trials and in order to support the go/no-go decision for these compounds, a target engagement biomarker was developed for drugs interfering with calcitonin gene-related peptide (CGRP). This resulted in a model referred to as the “capsaicin model” which has become an established tool for evaluating drugs targeting the CGRP pathway. Guided by data obtained from this target engagement biomarker, doses were selected to proceed more confidently into early efficacy trials.
Next to migraine, pain in general is an area with a large unmet medical need. In the search for more efficacious pain killing drugs and based on encouraging preclinical data, the TRP superfamily of cation channels has emerged as a new attractive target. In that context recently the TRP Research Platform Leuven (TRPLe) was founded. Being part of the TRP Research Platform Leuven, we are in the unique position to collaborate with established scientists of the KU Leuven and to develop new target engagement biomarkers for TRP channels identified as potentially involved in pain. As a result a biomarker for TRPA1 has been developed and additional biomarkers are under investigation.
Taken together, target engagement biomarkers have proven to be an invaluable asset fueling a data driven and more efficient rational drug development process.
For a better impression about our experience and challenging project in the area of pain and migraine you are kindly referred to our publication list.
As an Academic Research Organisation, in keeping with the Declaration of Helsinki, we are committed to making clinical trial results publically available. The timing of publications is obviously the result of a joint decision with the sponsor and with respect for the intellectual property involved.
For an extensive overview of previous research activities, you are kindly referred to our list of full papers published in peer-reviewed, international journals.