A randomized, double-blind trial investigating the efficacy and safety of intravenous neridronic acid in subjects with complex regional pain syndrome type I (CRPS-I)

INTERVENTION: Trade Name: Nerixia 100 mg/8 mL concentrate for solution for infusion Product Name: Neridronic acid 100 mg/8 mL concentrate for solution for infusion Product Code: GRT7013 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: NERIDRONATE SODIUM CAS Number: 80729‐79‐9 Current Sponsor code: GRT7013 Other descriptive name: Sodium neridronate hemihydrate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Concentrate for solution for infusion Route of administration of the placebo: Intravenous use CONDITION: Complex regional pain syndrome type I (CRPS‐I) ; MedDRA version: 18.0 Level: LLT Classification code 10064334 Term: Complex regional pain syndrome Type I System Organ Class: 100000004852 Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] SECONDARY OUTCOME: Secondary end point(s): Response to treatment, defined as a 30% reduction in the Pain Intensity Score from baseline to Week 12. ; Response to treatment, defined as a 50% reduction in the Pain Intensity Score from baseline to Week 12. ; Change in the Brief Pain Inventory (BPI) interference scale score from baseline to Week 12. ; The Patient Global Impression of Change (PGIC) questionnaire score at Week 12. ; Change in the EuroQol‐5 dimension 5 level (EQ‐5D‐5L) index score and visual analog scale (VAS) from baseline to Week 12. ; Timepoint(s) of evaluation of this end point: Response to treatment, change in the BPI, change in the EQ‐5D‐5L: Baseline to Week 12. ; Patient Global Impression of Change (PGIC) questionnaire score: Week 12. INCLUSION CRITERIA: • Informed consent signed. • Male or female participant between 18 years and 80 years of age. • A diagnosis of complex regional pain syndrome type I according to the clinical diagnostic criteria using the International Association for the Study of Pain clinical diagnostic criteria (Budapest criteria). • Baseline Pain Intensity Score of 4 or greater using an 11‐point Numerical Rating Scale referring to the CRPS‐affected limb. • In stable treatment and follow‐up therapy for CRPS type I for at least 1 month. • Participant has undergone a recent regular dental examination. • Women of child‐bearing potential must have a negative urine ß‐HCG pregnancy test at enrollment. • Women of child‐bearing potential must practice protocol defined acceptable methods of birth control during the trial. • Participants must be able to communicate meaningfully, be able to differentiate with regard to location and intensity of the pain, and be able to an PRIMARY OUTCOME: Main Objective: To demonstrate the efficacy of neridronic acid, versus placebo, in treatment of pain associated with CRPS‐I. Primary end point(s): The primary efficacy endpoint will be the change in the Pain Intensity Score from baseline to Week 12.; The Pain Intensity Score, related to the CRPS‐affected limb, will be determined from current pain intensity ratings, captured in an electronic diary, using an 11‐point numerical rating scale (NRS). Subjects will be asked to rate their current CRPS‐related pain intensity twice daily, once in the morning and once in the evening. Subjects rate their pain on this scale from 0 = “no pain” to 10 = “pain as bad as you can imagine”.; The Baseline Pain Intensity Score will be calculated as the average of 14 current pain intensity ratings obtained over the 7‐day baseline pain assessment phase prior to allocation to IMP, starting from the evening of Day ‐7 and concluding on the morning of Day 1 prior to IMP administration. At least 10 pain intensity ratings must be available for determination of the Baseline Pain Intensity Score. The Week 12 Pain Intensity Score will be determined in a similar manner (i.e., calculated from ratings obtained during the week prior to Visit 8, culminating with the morning rating on the day of Visit 8). All available ratings (of the 14 possible ratings in this time period) will be used in the calculation.; All pain intensity ratings for the primary endpoint will be in reference to the CRPS‐affected limb (or most painful limb at the time of screening if more than 1 limb is affected by CRPS). Secondary Objective: To assess the effect of neridronic acid on pain interference with daily function. ; To assess the effect of neridronic acid on Patient Global Impression of Change (PGIC) in response to treatment.; To assess the effect of neridronic acid on quality of life.; To assess the effect of neridronic acid on signs and symptoms of CRPS.; To assess the safety and tolerability of neridronic acid in subjects with CRPS‐I.; Timepoint(s) of evaluation of this end point: Pain Intensity Score from baseline to Week 12.