Safety of Intravenous Neridronic Acid in CRPS

Inclusion Criteria:

• Informed consent signed.

• Male or female participant at least 18 years of age at Visit 1.

• A diagnosis of complex regional pain syndrome according to the clinical diagnosticcriteria recommended by the International Association for the Study of Pain (IASP; "Budapest clinical criteria"), assessed at Visit 1. Signs and symptoms of CRPS mustapply to an affected limb (arm or leg) and must demonstrate asymmetry with respect tothe contralateral limb.

• Ongoing moderate to severe chronic pain, including a baseline current pain intensityscore of greater than or equal to 4 using an 11-point Numerical Rating Scale,referring to the CRPS-affected limb, at Visit 2 (prior to dosing).

• In stable treatment and follow-up therapy for CRPS for at least 1 month prior toallocation to treatment (Visit 2). Participants must have failed trials of at least 2treatments for CRPS, one of which must be a pharmacologic treatment.

• Women of child-bearing potential must have a negative urine beta-human chorionicgonadotropin (β-HCG) pregnancy test at Visit 1 and must be using 2 forms of medicallyacceptable contraception, including at least 1 highly effective method ofcontraception with a low failure rate, defined as less than 1% per year (e.g., oralcontraceptives or intrauterine device), and a second medically acceptable method suchas use of condoms with spermicide by their male partner. A barrier method alone is notacceptable. Highly effective methods of contraception must be used for at least 1month prior to Visit 2 and for the duration of the trial.

• Participants must be able to communicate meaningfully, be able to differentiate withregard to location and intensity of the pain, and be able to answer the questions inthe questionnaires used in this trial (assistance in filling out the questionnairesmay be provided, if required due to motor or other impairment).

Exclusion Criteria:

• Evidence of renal impairment (estimated glomerular filtration rate [eGFR] less than 60mL/min/1.73 m2 using the 2009 Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation [Levey et al. 2009] or a urinary albumin creatinineratio greater than 150 mg/g), based on central safety laboratory data obtained priorto Visit 2, or a history of chronic kidney disease. Note: a single repeat laboratorytest is allowed.

• Serum calcium or magnesium outside of the central laboratory's reference range, basedon central safety laboratory data obtained prior to Visit 2 (a single repeatlaboratory test is allowed); a history of hypocalcemia or a metabolic disorderanticipated to increase risk for hypocalcemia (e.g., hypoparathyroidism); concomitantuse of drug(s) with known potential to cause hypocalcemia (e.g., aminoglycosides).

• Vitamin D deficiency, defined as a 25(OH)D level less than 30 ng/mL, based on centralsafety laboratory data obtained prior to Visit 2 (up to 4 repeat laboratory tests areallowed). Participants with vitamin D deficiency should receive appropriatesupplementation during the enrollment period. A vitamin D level of at least 30 ng/mLmust be documented prior to allocation to investigational medicinal product (IMP).

• Corrected QT interval (according to Fridericia's formula; QTcF) greater than 470 ms (average of 3 electrocardiograms [ECGs] obtained at Visit 1); serum potassium outsidethe central laboratory's reference range at Visit 1; clinically unstable cardiacdisease, including: unstable atrial fibrillation, symptomatic bradycardia, unstablecongestive heart failure, active myocardial ischemia, or an indwelling pacemaker;evidence of complete left bundle branch block; complete atrioventricular block;history of Long QT Syndrome or a relative with this condition; or any other known riskfactor for torsade de pointes.

• Participants receiving medications with a known risk of torsades de pointes within 7days prior to allocation. Participants receiving selective serotonin re-uptakeinhibitor antidepressants (e.g., citalopram, escitalopram) or tricyclicantidepressants are eligible if the QT-interval values do not meet the exclusioncriteria, the medication was started at least 1 month prior to allocation, the dose isstable, and the dose is anticipated to remain stable until at least 4 days after thelast infusion of IMP.

• Anticipated requirement for treatment with oral or intravenous bisphosphonate foranother condition such as osteoporosis during the trial, or administration ofdenosumab (Prolia®) or other drugs affecting bone turnover or bone metabolism within 6months prior to Visit 1.

• History of any allergic or hypersensitivity reaction to neridronic acid or otherbisphosphonate, acetaminophen, or to vitamin D or calcium supplements.

• Recent tooth extraction or other invasive dental procedure (within 3 months prior toVisit 1), unhealed or infected extraction site, or significant dental/periodontaldisease (e.g., impacted molars, severe tooth decay, foci of infection) that maypredispose to need for tooth extraction or other invasive dental procedures during thetrial. Participants with indeterminate, suspicious or unreliable dental history, inthe opinion of the investigator, must undergo a dental examination prior to receivingtreatment.

• Evidence of denture-related gum trauma or improperly fitting dentures causing injury.

• Prior radiation therapy of the head or neck (within 1 year of Visit 1).

• History of malignancy within 2 years prior to Visit 1, with the exception of basalcell carcinoma.

• Use of nerve blocks, ketamine infusions, intravenous immunoglobulin, acupuncture,electromagnetic field treatment, or initiation/implementation of radiofrequencyablation or other sympathectomy procedures, or peripheral nerve stimulation within 6weeks prior to Visit 2.

• Evidence of current alcohol or drug abuse, or history of alcohol or drug abuse within 2 years of Visit 1, based on participant history and physical examination andaccording to the investigator's judgment.

• Any other severe medical condition, including severe depression, or any other severemood disorder, that in the opinion of the investigator may affect efficacy or safetyassessments or may compromise the participant's safety during trial participation.

• Women who are pregnant or breastfeeding.

• Elevated aspartate aminotransferase or alanine aminotransferase greater than 2-foldupper limit of normal, based on central safety laboratory data obtained at Visit 1, orcurrent evidence of chronic liver disease. Safety laboratory testing may be repeatedprior to Visit 2, and participants will be allowed in the trial if results of 2consecutive tests, at least 3 days apart, are less than or equal to 2-fold upper limitof normal.

• Participation in another investigational drug trial within 3 months prior to Visit 1or any previous trial with neridronic acid, with the exception of participants ofKF7013-01 who were assigned to placebo and did not receive neridronic acid.

• Participant is engaged in litigation related to their disability from CRPS in whichmonetary gain or loss (or other compensation) may affect their objective participationin the trial.

• Participants taking forbidden concomitant medications/therapies or not being able tofollow the rules of use of concomitant treatment.

• Participants incapable of signing the informed consent.