Welcome to the forum @aconnor
It would be helpful if you could get more of the error details, perhaps via About --> Show log --> Live --> Error. Google thinks this is a problem in TLS (but without details it’s hard to say which sort of error it is).
Error from mono: SSLV3_ALERT_HANDSHAKE_FAILURE has ideas for Duplicati, and a sample error.
Secure Socket Layer (SSL) / Transport Layer Security (TLS) gives some advice from the Mono project.
It would probably be good to be on a not-too-old mono (mono --version) should be at least 4.8, and a requirement for at least version 5 will be in a Duplicati Beta whenever the new Beta can get pushed out.