Randomized Double Blind Placebo Controlled Trial of Sodium Thiosulfate (STS) for the Treatment Pain With Calcific Uremic Arteriolopathy a Single Armed Extension Phase Prospectively Observe Lesion Progression in the Presence of STS

Efficacy of Sodium Thiosulfate (STS) compared to placebo, in reducing analgesic requirement
in subjects with calcific uremic arteriolopathy (CUA) during an initial 28-day treatment
phase.

Inclusion Criteria:

1. Males or females ≥18 years of age who are able to give informed consent.

2. Calcific uremic arteriolopathy (CUA), either newly-diagnosed or pre-existing,
currently on STS or not yet treated with STS and either not on pain medication or on
a stable pain medication regimen. The diagnosis of calciphylaxis can be made when:

- The following clinical features are all present, or two (2) of the following
clinical features and typical histopathological findings are present.

Clinical features:

1. A patient on chronic hemodialysis for chronic kidney disease or with a GFR of less
than 15/ml/min/1.73 m2

2. More than 2 painful and non-treatable skin ulcers with concomitant painful purpura

3. Painful and non-treatable skin ulcers on the trunk, extremities, or penis with
concomitant painful purpura

Histopathological findings by skin biopsy when 3 clinical findings are not present:

1. Necrosis and ulceration of the skin with calcification of the tunica media and
internal elastic membrane of small to medium-sized arterioles of dermis and
subcutaneous fat are essential for the diagnosis

2. Concentric stenosis due to edematous intimal thickening is also seen in the small to
medium-sized arterioles of dermis and subcutaneous fat

3. End stage renal disease (ESRD) on chronic maintenance hemodialysis.

4. Willingness to undergo washout of pre-existing STS treatment (if required by
treatment allocation) and to continue in a double blind treatment period of 4 weeks,
during which they might receive placebo.

5. Ability to comply with all study requirements.

Exclusion Criteria:

1. History of allergic or other adverse reaction to STS

2. Current treatment with STS for indications other than CUA (e.g. cyanide poisoning)

3. Currently on alternative treatment for CUA as listed below. Unless treatment has been
discontinued for at least 1 month prior to the screening visit.

1. Steroids

2. Hyperbaric Oxygen

3. Bisphosphonates

4. Pentoxifylline

5. Tissue Plasminogen Activator

6. Luciliar sericata larvae (maggot therapy)

7. On Cinacalcet for treatment for CUA (i.e. cinacalcet was either started or dose
increased after the appearance of lesions)

4. Any co-existing disease or problem that makes participation in the study unadvisable
for the patient or compromises integrity of the study

1. Cirrhosis of the liver

2. History of congestive heart failure (New York Heart Association class III or IV)
with multiple hospital admissions (at least 3 admissions in 6 months)

3. Persistent and uncontrolled metabolic acidosis

5. Chronic kidney disease or renal transplant patients with diagnosis of calciphylaxis
who are not on hemodialysis.

6. Any other disease or condition which, in the judgment of the Investigator, would
place a subject at undue risk by being enrolled in the trial, or cause inability to
comply with the trial