I had the same issue with my local installation of Splunk Enterprise 6.4.1 x64 running on Windows 10 x64.
The problem occurred when the twitter2 app reloads the page:
WARN LocalAppsAdminHandler - User 'admin' triggered the '_reload' action on app 'twitter2', and the following objects required a restart: restart_on_install
ERROR HttpClientRequest - HTTP client error: Read Timeout (while accessing http://127.0.0.1:8065/dj/en-us/twitter2/setup/)
What worked for me was to change the default appServerPorts in Splunk\etc\system\default\web.conf from 8065 to 0.
# list of ports to start python application servers on (although usually
# one port is enough) Set to 0 to instead run the application server
# directly as the web front end on 'httpport', separate from splunkd.
appServerPorts = 0
Hope it helps.
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