Proof of Concept Study: get in-human PK/BD data

First, you need to define your research question or hypothesis. Keep in mind that a PoC study is always conducted with a subtherapeutic dose on patients. Your research will therefore focus on indication (or potentially a specific mutation), biodistribution, on- and off-target uptake, and the areas at risk for potential side effects. Therapeutic effects cannot be achieved in a Proof of Concept trial, but the retrieved data will be beneficial in further clinical trials.

To retrieve PK/BD data you need to find a label that you can conjugate to your compound without affecting its characteristics and allowing good measurement in vivo. The labeled compound (tracer) will show absorption, distribution, metabolism, and excretion.

In this step, you will set the outlines for your study. Meaning:
• Set up inclusion and exclusion criteria;
• Choose your type of clinical trial;
• Choose the location(s) for your trial;
• Define your sample size;
• Define trial duration;
• Choose methods of data collection and validation;
• Define outcome analysis.
To learn more, download a clinical trial protocol template or example.

Trial feasibility

An important part of this step that is often overlooked is feasibility. It may happen that a clinical trial fails due to strict in- and exclusion criteria for the patients or a protocol design that is not feasible or a too large burden for the patient (and as a result patients refuse to participate). Don’t hesitate to use our 30 years of experience in this field. Contact us to discuss the best Proof of Concept examples related to your novel drug.

You will need regulatory approval before you can conduct your PoC clinical trial. Choosing to conduct your Clinical trials in The Netherlands has many benefits, including fast regulatory approval. The regulations for PoC clinical trials are different than for the other phases of clinical trials.
– You don’t need extensive tox data, in most cases an extended single dose toxicity study is sufficient. In case toxicity data of your compound is available and the label we use for molecular imaging is known, this step might not even be obligatory.
– You only need GLP material, as at TRACER we will label the GLP material in a GMP (hotlab) facility to manufacture a GMP product for use in PoC trials.

At step 4 you’ve designed the Proof of Concept study, obtained regulatory approval and are ready to move into the execution of the first in human clinical trials. Meaning the recruitment of participants, data collection, analysis, safety monitoring and interpretation and reporting.

The Proof of Concept study referring to the Phase 0 POC clinical trial is approved by the FDA. The focus of Phase 0 first in human clinical trials is to evaluate the targeting of a new drug in patients. Depending on the Proof of Concept study level of evidence, there can be a go/no-go decision made to move a drug into subsequent clinical trials.

A Proof of Concept trial is also known as Phase 0. Meaning the PoC clinical trial comes before Phase I-IV. It is a clinical study and the first in human clinical trial.

Comparing Proof of Concept clinical trial with Phase 1, the cohort is one of the major differences. Where Phase 1 is conducted on a large number of healthy volunteers, the PoC study is conducted on a small number of patients (+/- 10). Since PK/BD data can differ between healthy volunteers and the target population, data from the Proof of Concept clinical trial can be more reliable than Phase 1.

Phase 2 in clinical trials has the objective to test your drug’s efficacy. Because you already investigate this with your PoC study, you can move with more confidence into this phase of clinical trials. You also have a better understanding of the indication your drug targets. This means you can select your participants better, get more reliable data, and your chances of success increase.

As you may know by now, PoC stands for Proof of Concept, but what is the meaning of PoV and how are they different? PoV stands for Proof of Value, meaning the business value of your concept. Therefore, PoV will focus on financial and strategic benefits. The difference between a PoC and a PoV is that the PoC has a narrow, technical-orientated scope, while PoV has a broader scope focused on business value.

If you are looking for Proof of Concept examples, then you should read our case study in oncology.

How do you write a Proof of Concept study? In general, you outline the purpose, methodology, and expected outcome. A structure that can be used is the following:
• Introduction
• Methodology/study design
• Execution/Implementation
• Data analysis
• Results and discussion
• Conclusion

Remember what your main goal for the Proof of Concept study is: gathering data that prove the mechanism of your novel drugs. The Proof of Concept study design and sample size both depend on what proof you need.