Phase 3 Study of SNF472 for Calciphylaxis

Study Overview
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Brief Summary
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The primary objectives are to assess the efficacy, safety, and tolerability of SNF472 compared to placebo when added to background care for the treatment of calciphylaxis (CUA).

Detailed Description
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The formation and growth of calcified deposits in arterioles and other small blood vessels appears to be fundamental to the development of CUA especially in end stage renal disease patients. This phase 3 double-blind, randomized, placebo-controlled study is designed to assess the effect of SNF472 when added to background care to improve wound healing, as evaluated using Bates-Jensen Wound Assessment Tool (BWAT) scoring and pain as reported by the subject using a VAS scale. The study consists of a double-blind, randomized, placebo controlled period of 12 weeks followed by an open-label period of 12 weeks.. .

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of SNF472 When Added to Background Care for the Treatment of Calciphylaxis

Conditions
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Calciphylaxis, Calcific Uremic Arteriolopathy

Intervention / Treatment
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* Drug: Experimental: SNF472
* Drug: Placebo Comparator: Placebo
* Drug: Experimatenl SNF472 (Open-label)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male subjects, 18 years of age or older Receiving maintenance HD in a clinical setting for at least 2 weeks prior to screening Clinical diagnosis of CUA by the Investigator including ≥1 CUA lesion with ulceration of the epithelial surface CUA wound-related pain shown by a Pain VAS score ≥50 out of 100 Primary lesion that can be clearly photographed for the purpose of protocol-specified wound healing assessments. Willing and able to understand and sign the informed consent form and willing to comply with all aspects of the protocol Exclusion Criteria: History of treatment with bisphosphonates within 3 months of baseline Severely ill subjects without a reasonable expectation of survival for at least 6 months Subjects with a scheduled parathyroidectomy during the study period Expectation for kidney transplant within the next 6 months based on Investigator assessment or identification of a known living donor Pregnant or trying to become pregnant, currently breastfeeding, or of childbearing potential (including perimenopausal women who have had a menstrual period within one year) and not willing to comply with protocol required contraception criteria Significant noncompliance with dialysis History of active malignancy within the last year with the exception of localized basal cell or squamous cell carcinoma Clinically significant illness other than CUA within 30 days Participation in an investigational study and receipt of an investigational drug or investigational use of a licensed drug within 30 days prior to screening. History or presence of active alcoholism or drug abuse as determined by the Investigator within 6 months Mental impairment, current significant psychiatric disease, or other conditions or circumstances that would make the subject unlikely to complete the study or comply with the study procedures. Subjects whose CUA lesions exhibit significant improvement, in the opinion of the Investigator, between the first and second screening visit

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: SNF472 (Double-Blind Period)<br>Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. | Drug: Experimental: SNF472<br>* Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks<br>|
| Placebo Comparator: Placebo (Double-Blind Period)<br>Matching placebo (saline) diluted in 100 mL physiological saline. | Drug: Placebo Comparator: Placebo<br>* Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks<br>* Other names: Saline;|
| Experimental: SNF472 (Open-Label)<br>Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. | Drug: Experimatenl SNF472 (Open-label)<br>* Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the BWAT-CUA score for the primary lesion | The Bates Jensen Wound Assessment Tool (BWAT) CUA score ranges from a minimum score of 8 (best) to a maximum score of 40 (worst) | Basline to week 12 | 
| Change in Pain VAS score | The Pain Visual Analog Scale (VAS) score ranges from a minimum score of 0 (no pain) to 100 (worst possible pain) | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Wound-QoL score | The Wound Quality of Life scale is a validated self-assessment tool that has been shown to be feasible for assessing health-related quality of life in patients with chronic wounds. Lower scores are associated with a better quality of life as reported by the patient. | Basline to Week 12 | 
| Change in the BWAT total score for the primary lesion | The Bates Jensen Wound Assessment Tool (BWAT) score ranges from a minimum score of 9 (best) to a maximum score of 65 (worst) score | Baseline to Week 12 | 
| Qualitative wound image evaluation for the primary lesion |  | Baseline to Week 12 | 
| Rate of change in opioid use as measured in morphine milligram equivalents (MME) |  | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcific Uremic Arteriolopathy, Wound, ESRD, Calciphylaxis