Phase 3 Study of SNF472 for Calciphylaxis (Calciphyx)

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

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).

Study Overview

• Status: Completed
• Conditions: Calciphylaxis; Calcific Uremic Arteriolopathy
• Intervention / Treatment: Drug: Experimental: SNF472; Drug: Placebo Comparator: Placebo; Drug: Experimatenl SNF472 (Open-label)

Detailed Description

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.. .

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Clinques Universitaries de Bruxelles Hopital
  • Leuven, Belgium
    • UZ Leuven
  • Roeselare, Belgium
    • AZ Delta
• Germany
  • Berlin, Germany
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Düsseldorf, Germany
    • DaVita Deutschland AG
  • Baden Wuerttemberg
    • Villingen-Schwenningen, Baden Wuerttemberg, Germany
      • Nephrologischen Zentrum Villingen-Schwenningen
• Poland
  • Bydgoszcz, Poland
    • Centrum Dializ Fresenius, Ośrodek Dializ nr 10 w Bydgoszczy 85-826
  • Krakow, Poland
    • Centrum Dializ Fresenius, Ośrodek Dializ nr 18 w Krakowie..
  • Miechów, Poland
    • DaVita Sp. z o.o., Stacja Dializ w Miechowie
  • Radom, Poland
    • Centrum Dializ Fresenius Ośrodek Dializ nr 32 w Radomiu 26-617 .
  • Łódź, Poland
    • Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego w Lodzi Stacja Dializ,
• Spain
  • Barcelona, Spain, 08025
    • Fundacio Puigvert
  • Barcelona, Spain, 08036
    • University of Barcelona Hospital Clinic
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
• United Kingdom
  • London, United Kingdom, SE59RS
    • Kings College Hospital
  • Devon
    • Exeter, Devon, United Kingdom
      • Royal Devon and Exeter Hospital (Wonford)
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Salford Royal NHS Foundation Trust
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Leicester General Hospital
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom
      • Queen Elizabeth University Hospital Campus
  • West Midlands
    • Birmingham, West Midlands, United Kingdom
      • Queen Elizabeth Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85035
      • AKDHC Medical Research Services
  • California
    • El Centro, California, United States, 92243
      • California Institute of Renal Research
    • Escondido, California, United States, 92027
      • California Institute of Renal Research
    • Glendale, California, United States, 91204
      • Kidney Disease Medical Group
    • Lynwood, California, United States, 90260
      • DaVita Clinical Research
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
    • San Diego, California, United States, 92111
      • Fresenius Kidney Care
    • San Dimas, California, United States, 91773
      • North America Research Institute
    • Vacaville, California, United States, 95687
      • Amicis Research Center
  • Colorado
    • Denver, Colorado, United States, 80230
      • Colorado Kidney Care
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Boca Nephrology, PA
    • Hollywood, Florida, United States, 33024
      • DaVita Clinical Research
    • Spring Hill, Florida, United States, 34667
      • Novel Outcomes Research
    • Tampa, Florida, United States, 33614
      • DaVita Clinical Research
    • Tampa, Florida, United States, 33614
      • Fresenius Kidney Care
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Pontiac, Michigan, United States, 48341
      • Michigan Kidney Consultants
    • Roseville, Michigan, United States, 48066
      • DaVita Clinical Research
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • DaVita Clinical Research
  • Mississippi
    • Brookhaven, Mississippi, United States, 39601
      • Fresenius Kidney Care
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • DaVita Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • DaVita Clinical Research
    • Reno, Nevada, United States, 89511
      • Fresenius Kidney Care
  • New York
    • Bronx, New York, United States, 10461
      • DaVita Clinical Research
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • DaVita Clinical Research
    • Durham, North Carolina, United States, 22704
      • Fresenius Kidney Care
    • Winston-Salem, North Carolina, United States, 27101
      • Piedmont Dialysis Center
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Hypertension Nephrology Consultants, Inc
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Fresenius Kidney Care
    • Chester, Pennsylvania, United States, 19013
      • DaVita Clinical Research
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Fresenius Kidney Care
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center
  • Texas
    • Houston, Texas, United States, 77004
      • DaVita Clinical Research
    • San Antonio, Texas, United States, 78212
      • Clinical Advancement Center
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • DaVita Clinical Research
    • Norfolk, Virginia, United States, 23502
      • DaVita Clinical Research
    • Roanoke, Virginia, United States, 24014
      • Fresenius Kidney Care
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • DaVita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute 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). BWAT-CUA= Bates-Jensen Wound Assessment Tool-Calcific Uremic Arteriolopathy	from Baseline to Week 12
Absolute Change in Pain Visual Analog Score	The Pain Visual Analog Scale (VAS) score ranges from a minimum score of 0 (no pain) to 100 (worst possible pain).	from Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in the Wound-Quality of Life 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. The score is computed by averaging the 17 items on impairments assessed on a scale of 0 to 4 for the preceding 7 days. A global score can only be computed if at least 75% of the items have been answered, i.e., at least 13 in 17 items are valid. All the available items' scores were added up and divided by 17. In case of missing assessments for any one of the 17 items, the median of the scores for a particular item within the associated randomized treatment group was used for the imputation purposes. As the absolute change from baseline is reported, a higher negative value is associated with a higher improvement of quality of life.	from Baseline to Week 12
Absolute 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.	from Baseline to Week 12
Qualitative Wound Image Evaluation for the Primary Lesion	A qualitative assessment (Worsened, Equal to, or Improved Relative to Baseline) was assigned	at Week 12
Rate of Change in Opioid Use as Measured in Morphine Milligram Equivalents (MME)	Change from baseline in opioid use MME = Morphine Milligram Equivalents The calculation of the pre-specified list of opioids was based on the formula: strength per unit × (number of units/days supply) × MME conversion factor = MME/day, as specified in the opioid MME conversion guide (CMS, 2017). The maintenance opioid dose was defined as the average daily opioid dose in MME during the 7-day period prior to Screening Visit 2. To assess the extent to which opioid use may have differed between randomized treatment groups over time, the change from baseline in daily average MME value was analyzed.	from Baseline to Week 12

Collaborators and Investigators

• Sponsor: Sanifit Therapeutics S. A.
• Investigators: Study Director: Alex Gold, MD, Sanifit Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): October 24, 2022

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: ESRD; Wound; Calciphylaxis; Calcific Uremic Arteriolopathy
• Additional Relevant MeSH Terms: Metabolic Diseases; Calcium Metabolism Disorders; Calcinosis; Calciphylaxis
• Other Study ID Numbers: SNFCT2017-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No