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

Study Overview
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Brief Summary
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This 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.

Detailed Description
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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.

Official Title
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A Phase 3, Intravenous Sodium Thiosulfate for Acute Calciphylaxis Treatment: A Multicenter, Randomized, Double-blind, Placebo-controlled, Clinical Trial

Conditions
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Calciphylaxis

Intervention / Treatment
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* Drug: Sodium Thiosulfate
* Drug: Placebo-Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Thiosulfate<br>Sodium Thiosulfate Injection (25 grams sodium thiosulfate) | Drug: Sodium Thiosulfate<br>* Intravenous Sodium Thiosulfate Injection (25 grams sodium thiosulfate) to be administered each hemodialysis session (3 times weekly) for 3 weeks<br>* Other names: Intravenous Sodium Thiosulfate Injection;|
| Placebo Comparator: Placebo-Normal Saline<br>0.9% sodium chloride injection, USP (normal saline) | Drug: Placebo-Normal Saline<br>* Placebo: to be administered each hemodialysis session (3 times weekly) for 3 weeks<br>* Other names: 0.9% sodium chloride solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with 30% improvement in pain severity | To compare the effects of treatment with intravenous Sodium Thiosulfate Injection vs. placebo for the proportion of patients (responders) who achieve a ≥ 30% reduction based upon pain intensity score (modified BPI/SF). | randomization to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint-a: Number of patients with stabilization or improvement in calciphylaxis skin lesions. | Proportion of patients who achieve improvement or stabilization (i.e., not worsening) of skin lesions. | randomization to 3 weeks | 
| Secondary Endpoint-b: Occurence of surgical debridement of skin lesions and/or amputation. | Occurence of surgical debridement of skin lesions and/or amputation. | during week 3 | 
| Secondary Endpoint-c: Occurrence of surgical debridement of skin lesions and/or amputation. | Occurrence of surgical debridement of skin lesions and/or amputation. | randomization to 3 weeks | 
| Secondary Endpoint-d: Time to achieve ≥ 30% improvement in pain severity | Time in days when a patient achieves a ≥ 30% improvement based upon pain intensity score (modified BPI/SF). | randomization to 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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calciphylaxis, calcific uremic arteriolopathy, calcinosis, calcium metabolism disorders, metabolic diseases, sodium thiosulfate