Phase 3 Study of SNF472 for Calciphylaxis

Phase 3

Completed

• Conditions: Calciphylaxis; Calcific Uremic Arteriolopathy
• Interventions: Drug: Experimatenl SNF472 (Open-label)

• Registration Number: NCT04195906
• Lead Sponsor: Sanifit Therapeutics S. A.

Brief Summary

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

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 Timeline

• Study First Submitted: 2019-12-10
• Study First Submitted QC: 2019-12-10
• Study First Posted: 2019-12-12
• Study Start: 2020-02-12
• Primary Completion: 2022-10-24
• Study Completion: 2022-10-24
• Results First Submitted: 2023-11-15
• Status Verified: 2023-12
• Results First Submitted QC: 2024-01-25
• Last Update Submitted: 2024-01-25
• Results First Posted: 2024-02-20
• Last Update Posted: 2024-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SNF472 (Open-Label)	Experimatenl SNF472 (Open-label)	Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline.

Primary Outcome Measures

Name	Time	Method
Absolute Change in the BWAT - CUA Score for the Primary Lesion	from Baseline to Week 12	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
Absolute Change in Pain Visual Analog Score	from Baseline to Week 12	The Pain Visual Analog Scale (VAS) score ranges from a minimum score of 0 (no pain) to 100 (worst possible pain).

Secondary Outcome Measures

Name	Time	Method
Absolute Change in the Wound-Quality of Life Score	from Baseline to Week 12	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.
Absolute Change in the BWAT Total Score for the Primary Lesion	from Baseline to Week 12	The Bates Jensen Wound Assessment Tool (BWAT) score ranges from a minimum score of 9 (best) to a maximum score of 65 (worst) score.
Rate of Change in Opioid Use as Measured in Morphine Milligram Equivalents (MME)	from Baseline to Week 12	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.
Qualitative Wound Image Evaluation for the Primary Lesion	at Week 12	A qualitative assessment (Worsened, Equal to, or Improved Relative to Baseline) was assigned

Trial Locations

Locations (37)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Clinical Advancement Center; 🇺🇸 San Antonio, Texas, United States

AKDHC Medical Research Services; 🇺🇸 Phoenix, Arizona, United States

California Institute of Renal Research; 🇺🇸 Escondido, California, United States

Fresenius Kidney Care; 🇺🇸 Roanoke, Virginia, United States

Colorado Kidney Care; 🇺🇸 Denver, Colorado, United States

Boca Nephrology, PA; 🇺🇸 Boca Raton, Florida, United States

Novel Outcomes Research; 🇺🇸 Spring Hill, Florida, United States

Michigan Kidney Consultants; 🇺🇸 Pontiac, Michigan, United States

Piedmont Dialysis Center; 🇺🇸 Winston-Salem, North Carolina, United States

Clinques Universitaries de Bruxelles Hopital; 🇧🇪 Bruxelles, Belgium

DaVita Deutschland AG; 🇩🇪 Düsseldorf, Germany

Nephrologischen Zentrum Villingen-Schwenningen; 🇩🇪 Villingen-Schwenningen, Baden Wuerttemberg, Germany

Charite Universitaetsmedizin Berlin - Campus Charite Mitte; 🇩🇪 Berlin, Germany

Fundacio Puigvert; 🇪🇸 Barcelona, Spain

University of Barcelona Hospital Clinic; 🇪🇸 Barcelona, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Córdoba, Spain

Leicester General Hospital; 🇬🇧 Leicester, Leicestershire, United Kingdom

Salford Royal NHS Foundation Trust; 🇬🇧 Salford, Greater Manchester, United Kingdom

Queen Elizabeth Hospital; 🇬🇧 Birmingham, West Midlands, United Kingdom

Kings College Hospital; 🇬🇧 London, United Kingdom

Kidney Disease Medical Group; 🇺🇸 Glendale, California, United States

DaVita Clinical Research; 🇺🇸 Wauwatosa, Wisconsin, United States

Apex Research of Riverside; 🇺🇸 Riverside, California, United States

North America Research Institute; 🇺🇸 San Dimas, California, United States

Hypertension Nephrology Consultants, Inc; 🇺🇸 Columbus, Ohio, United States

Amicis Research Center; 🇺🇸 Vacaville, California, United States

Royal Devon and Exeter Hospital (Wonford); 🇬🇧 Exeter, Devon, United Kingdom

Queen Elizabeth University Hospital Campus; 🇬🇧 Glasgow, Strathclyde, United Kingdom

DaVita Sp. z o.o., Stacja Dializ w Miechowie; 🇵🇱 Miechów, Poland

Knoxville Kidney Center; 🇺🇸 Knoxville, Tennessee, United States

Centrum Dializ Fresenius, Ośrodek Dializ nr 10 w Bydgoszczy 85-826; 🇵🇱 Bydgoszcz, Poland

UZ Leuven; 🇧🇪 Leuven, Belgium

AZ Delta; 🇧🇪 Roeselare, Belgium

Centrum Dializ Fresenius, Ośrodek Dializ nr 18 w Krakowie..; 🇵🇱 Krakow, Poland

Centrum Dializ Fresenius Ośrodek Dializ nr 32 w Radomiu 26-617 .; 🇵🇱 Radom, Poland

Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego w Lodzi Stacja Dializ,; 🇵🇱 Łódź, Poland