TGN1412 was a drug being trialled in humans, which experienced issues during the phase I trial.
The drug was found to bind very strongly to the participants target receptors, and resulted in near-catastrophic organ failure. This led to the participants administered with the active drug being transferred to intensive care, where they remained for many months.
Due to the failures of this trial, additional safety precautions are now in place. Initially, only 1 participant is administered the drug first, allowing immediate side effects to be identified, reducing the number of impacted individuals if there are issues with the drug. The dose administered during phase I trials is much lower than would be used clinically, producing the minimal anticipated biological effect. Although a lower dose was used in TGN1412, it was considerably higher than necessary. Receptor occupancy studies may be conducted prior to a human trial commencing, allowing the binding affinity to be determined. Typically, this compares the drug being trialled against TGN1412 (which acts as a reference or baseline).
Biological drugs are different to small molecules, and changes have now been made to drug trial protocols to improve safety. This leads to better outcomes for the participants, and reduces the likelihood of things going wrong.