A Phase 3 Clinical Trial of Intravenous Sodium Thiosulfate in Acute Calciphylaxis Patients

This Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial will
evaluate the efficacy and safety of intravenous Sodium Thiosulfate Injection for treatment of
acute calciphylaxis-associated pain in chronic hemodialysis patients. Acute calciphylaxis-
associated pain intensity will be the primary outcome measure.

Inclusion Criteria:

- Informed of the investigational nature of the study and sign written informed consent

- Willing and able to adhere to all study-related procedures, including adherence to
study medication regimen

- Male or female ≥18 years old

- End-stage renal disease on chronic hemodialysis

- Calciphylaxis with active skin lesion(s) of any morphological appearance (including
but not limited to livedo, induration, ulceration, etc.) and tissue histology review
consistent with calciphylaxis diagnosis. Histological features consistent with
calciphylaxis will include soft tissue calcification, microthrombosis, and/or
fibrointimal hyperplasia of dermal arterioles

- Acute pain associated with calciphylaxis lesions pain intensity score of ≥ 5 at
initial screening on the modified BPI/SF scale

- Women of childbearing potential must have a pregnancy test (urine or serum [if
anuric]) at screening and not be pregnant and willing to use an acceptable method of
contraception for the entire duration of the study (3 weeks)

Exclusion Criteria:

- Peritoneal dialysis patients

- Current congestive heart failure exacerbation

- Baseline abnormalities related to QT prolongation (corrected QT interval > 470 ms),
hypocalcemia (serum albumin-corrected calcium < 8 mg/dL ), metabolic acidosis (serum
bicarbonate < 18 mmol/L, hypotension (resting systolic blood pressure while seated <
80), or interdialytic weight gain ≥ 4.0 kg

- History of ventricular arrhythmias including ventricular fibrillation or ventricular
tachycardia associated with shortness of breath, dizziness, hypotension, or syncope

- Any prior (within the past 30 days) or current intravenous Sodium Thiosulfate
Injection treatment

- Other investigational agent (drug, biologic, or device) study within the past 30 days
and/or for the duration of the trial

- Pregnant or lactating women

- History of allergy to sulfites, thiosulfate, or any component in Sodium Thiosulfate
Injection (sulfa allergy is not an exclusion criterion)

- Significant other acute or chronic concomitant diseases (including but not limited to
hepatic, cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema,
pulmonary embolism) that would be inconsistent with survival for at least 3 months

- Other serious concurrent or recent medical or psychiatric condition which, in the
opinion of the Investigator, makes the patient unsuitable for participation in this
study

- Ongoing application of dialysate admixed with iron salt e.g. ferric pyrophosphate
during the entire trial period (patients who are on dialysate admixed with iron salt
at screening are eligible if dialysate admixed with iron salt can be substituted with
non-iron based dialysate and patients can be maintained on non-iron based dialysate
therapy for the entire duration of trial period)

- Recent (within 1 week) history of surgical parathyroidectomy or scheduled for surgical
parathyroidectomy during the course of the study

- History of opioid addiction