Amendment 01: The principal change in this protocol amendment was a reduction in cumulative dose levels from neridronic acid 400 mg and 200 mg to neridronic acid 250 mg and 125 mg, respectively. Due to the reduction in cumulative dose levels, the amount of drug infused during each infusion (of active study medication) was reduced from 100 mg to 62.5 mg. To preserve the use of the packaged clinical trial supplies consisting of ampules containing neridronic acid 100 mg in 8 mL volume, the volume transferred from the ampule to the infusion bag containing normal saline was reduced to 5 mL. A witness was required for the transfer procedure to ensure the correct dose was given. Consistent with the lower dose per infusion, the infusion time was reduced from 3 hours to 2 hours.

Amendment 02: • The requirements for discontinuation of IMP were modified to allow for resumption of treatment upon further assessment of laboratory changes or other findings within 7 days, if changes were transient and/or considered to be not clinically significant. This included modification of the procedure to prevent discontinuation of treatment due to spurious changes in eGFR determined from the local laboratory creatinine values or due to clinically insignificant variations in serum calcium values. The changes were implemented to improve the benefit/risk for subjects who would otherwise be discontinued due to transient, variable, or arbitrary findings. In situations where treatment was temporarily discontinued, the final IMP infusion had to be completed by 21 days after the first infusion. • Trial termination following last subject allocated was changed from 3 months to 6 months to provide a minimum of 6 months follow-up for all subjects. This provided additional long-term follow-up data to support evaluation of safety and the duration of effect of neridronic acid. • The enrollment period was extended from 28 days to 60 days (up to 90 days with approval of the sponsor) to provide sufficient time to meet requirements for repletion of vitamin D levels and to add flexibility due to issues in visit scheduling. • In consideration of the fact that CRPS is a rare disease, re-enrollment was permitted for subjects who previously failed enrollment due to reasons that were no longer included under protocol amendment 02, provided the subject met all current inclusion/exclusion criteria. Other re-enrollment was permitted (e.g., due to an erroneous enrollment failure), upon sponsor approval, provided the subject met all inclusion/exclusion criteria. • The enrollment cap for the subgroup of patients with CRPS duration ≥1 year was changed to 85% due to difficulty in enrolling subjects with duration of disease <1 year.