Some users get blank OWA page after logon

Hello all,

I have the following strange issue:

Some, but not all of our users have issues opening OWA. After logging in, the web page stays blank.

In IIS on the CAS server, I see a HTTP 500 error. On the MBX server, I see the following error (multiple times) at exact the moment the user logs on:

Event 65, MSExchange OWA

An error occurred while the Outlook Web App configuration settings were being loaded. Virtual directory: "owa". Web site: "Exchange Back End".
Error message:
"An IIS directory entry couldn't be created. The error message is Access is denied.
. HResult = -2147024891"

The users do not have other issues. Mail syncs perfectly in Outlook (2013) and on mobile devices.

Environment: Exchange 2013 SP1 (2x CAS servers, load balanced, 3x MBX servers in a DAG). 

How can I troubleshoot this?

Regards,

Stephan van der Plas

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