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The value of Phase 0 imaging data to your IND application

Maarten Brom, PhD

If you want to start your Phase 1 study in the United States, you need to submit an Investigational New Drug (IND) application to the FDA. You need to show that your new drug is reasonably safe for initial testing in humans to get it approved. In general, the safety assessment is performed by evaluation of preclinical feasibility and toxicity data. With a Phase 0 imaging study you could provide more detailed in-human data instead and give yourself a better shot at getting your IND approved.

Replace your extensive animal studies with a Phase 0 imaging study.

Once you have promising preclinical data, you’d want to move your drug to the next development phase. Or better said in human testing. If you follow the classical drug development process this usually means initiating a Phase 1 study in healthy volunteers.

To start your Phase 1 study in the United States you first need to obtain IND approval from the FDA. An IND submission requires you to gather data through extensive animal pharmacology and toxicology studies, also in large animals. These studies are time consuming and costly. Especially if you consider the fact that this data is no guarantee that your drug is effective in humans.

This IND requirement changes once you decide to conduct a Phase 0 imaging study instead. As you test your (new) drug within the microdosing principle, you only need to conduct limited pharmacology and toxicology studies. This saves you considerable amount of time, as you do not have to wait with your first-in-human study until you finished your animal models.

Use in-human safety data in your IND application to increase approval rate.

The aim of an IND application is to show that your (new) drug is reasonably safe for the use in clinical trials. You may proof this with (foreign) clinical data of the drug. This is where you should use your Phase 0 imaging study data.

More specifically, in a Phase 0 imaging study you first label your (new) drug with a radionuclide or fluorescent dye. Next you use imaging techniques to visualize the biodistribution of your new drug in the patient population of interest. The biodistribution shows you the accumulation of your drug in the target tissue (on-target) and other tissues (off-target).

You can confirm the preclinical findings on your drugs’ pharmacology based on this on- and off-target data. More importantly, you are also able to estimate the toxicity profile of your drug. In other words, if you find low uptake of your drug in non-target tissue, it is less likely that you will observe toxicity. Also, the exposure of patients to your new drug, albeit in low doses, will give you a direct indication of potential side effects.

Adding in-human pharmacology and toxicity data to your IND submission significantly strengthens your application. Why? Well, you are treating humans, not mice, so in-human data will always be more powerful than preclinical animal data.

Submit a better designed Phase 1 clinical protocol.

Every IND application also includes a (draft) Phase 1 study protocol. As you now already know the biodistribution and pharmacokinetics of your drug in humans, you can design your Phase 1 study more efficient. For example, you can predict the toxicity profile and estimate the doses to use. You can also give the FDA a more accurate estimation of the timing of the interventions during the trial. Overall, your IND application will consist of well-founded information on the safety, pharmacology and study design based on the findings of the phase 0 study.

So, when you perform a Phase 0 imaging trial you can strengthen the IND application with in-human data. This will get you an easier and faster IND approval.


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