Assessment of the anti-inflammatory efficacy of new drugs in humans during early drug development is difficult. In general, only in phase II of drug development, the therapeutic efficacy of such drug can be estimated. Assessment of potential therapeutic efficacy in earlier stages greatly stimulates and facilitates a more rational development of anti-inflammatory compounds. Therefore, CHDR offers reliable and accurate methodology to induce inflammatory responses in whole blood or isolated immune cells, allowing evaluation of the immune-modulating effects of new drugs in the earliest phase: in vitro/ex vivo inflammatory challenges. CHDR provides a GCP- and GCLP-compliant environment that combines all key items for successful drug development. We offer state-of-the art assays carried out by fixed partner labs, ensuring the highest content (academic) quality combined with the mandatory process quality. Importantly, CHDR is an acknowledged and respected partner of the main Dutch academic medical centers and multiple teaching hospitals, which allows access to key opinion leaders in various specializations in internal medicine, and an established network allowing access to relevant patient populations. CHDR has extensive collaborations with experts in the field of PK/PD modeling, systems biology, and systems pharmacology, allowing the most efficient and advanced analysis of collected data. As a result of this integrated service by CHDR, the client gets all answers to its questions quickly, without the hassle of dealing with multiple parties.
Developing powerful and innovative new treatments
Advances in both basic and clinical immunology during the past few decades are now rapidly being translated into effective new treatments for a wide range of conditions. Because the immune system is highly complex, all new immune-based treatments must be evaluated thoroughly. Moreover, early clinical development of new immunologically active drugs requires both scientific and clinical expertise in order to ensure the subjects’ safety and to maximise the resulting clinical and economic benefits. CHDR is committed to overcoming the scientific and practical challenges associated with the early clinical development of these new treatments. Specifically, several new methods for evaluating immunologically active compounds have been developed and validated at CHDR. With access to in vivo, in vitro, and ex vivo systems, we can systematically evaluate the efficacy and safety of new test compounds in the earliest stages of development.
Bridging preclinical and clinical drug development
We are particularly interested in taking the step from preclinical research to clinical drug development. We carefully select, validate, and apply a wide range of biomarkers, challenge models, and clinical strategies to find answers to our sponsors’ questions. A well-informed translational strategy also increases the safety of our subjects and the safety of participants in future clinical trials. Given the complexity of the immune response, our knowledge-intensive approach is particularly important in the field of immunology.
CHDR has its roots in academia, and our staff are closely involved in research. In addition, we have an extensive network of research groups and clinicians who share their expertise with us when needed. We also have direct access to several highly specialised laboratories, in addition to our own research facilities. This unique combination of resources and expertise allows us to offer each sponsor a tailor-made approach to translational drug development.
Using cutting-edge immunological biomarkers to measure a drug’s effects
We use in vitro, ex vivo, and in vivo approaches to study the effects of new test compounds. One powerful approach involves the use of biomarkers. We have an extensive library of biomarkers, which we are continuously expanding; do not hesitate to contact us if you have any specific questions or requests.
Our general approach is to build upon the groundwork laid by the preclinical scientists who originally developed a compound or treatment. Wherever possible, we attempt to include the tests and/or procedures that were used in preclinical testing. The primary goal in early clinical drug development is to demonstrate a pharmacological effect, ideally using highly sensitive biomarkers. However, because the setting in these early studies often differs somewhat from clinical practice, these biomarkers may not necessarily be the same biomarkers that are commonly used in a clinical setting. In this context, the primary goal when selecting a biomarker is to demonstrate that the drug reaches its intended target. Of course, if desired we can also include clinically relevant biomarkers.
In vitro measurements using human cells
Because CHDR has close ties with Leiden University Medical Center and other hospitals, it is relatively easy to obtain fresh human samples from specific patient populations and healthy volunteers. These biological materials can then be used in an in vitro setting to measure the pharmacological activity of a test compound. In some cases, the immunological effects of a compound on whole blood samples, isolated peripheral blood cells, or skin samples can be determined by measuring changes in the cells’ physiology. Sometimes, however, this will not be sufficient to demonstrate that the compound has its intended effect. For example, a compound that was designed to modify the inflammatory response by acting on a specific pathway may not have any measurable effect on non-activated blood cells. In this case, we first need to activate the inflammatory response using the relevant pathway in our so-called ‘challenge’ model; the compound’s effects on these activated cells can then be measured.