Phase 3 Study of SNF472 for Calciphylaxis

Calciphylaxis Clinical Trial

— Calciphyx  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04195906
• Other study ID #: SNFCT2017-06
• Status: Completed
• Phase: Phase 3
• Start date: February 12, 2020
• Est. completion date: October 24, 2022

Study information

• Verified date: December 2023
• Source: Sanifit Therapeutics S. A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.. .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: October 24, 2022
• Est. primary completion date: October 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Calcific Uremic Arteriolopathy
• Calciphylaxis

Intervention

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
Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks
• 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

Locations

Country	Name	City	State
Belgium	Clinques Universitaries de Bruxelles Hopital	Bruxelles
Belgium	UZ Leuven	Leuven
Belgium	AZ Delta	Roeselare
Germany	Charite Universitaetsmedizin Berlin - Campus Charite Mitte	Berlin
Germany	DaVita Deutschland AG	Düsseldorf
Germany	Nephrologischen Zentrum Villingen-Schwenningen	Villingen-Schwenningen	Baden Wuerttemberg
Poland	Centrum Dializ Fresenius, Osrodek Dializ nr 10 w Bydgoszczy 85-826	Bydgoszcz
Poland	Centrum Dializ Fresenius, Osrodek Dializ nr 18 w Krakowie..	Krakow
Poland	Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego w Lodzi Stacja Dializ,	Lódz
Poland	DaVita Sp. z o.o., Stacja Dializ w Miechowie	Miechów
Poland	Centrum Dializ Fresenius Osrodek Dializ nr 32 w Radomiu 26-617 .	Radom
Spain	Fundacio Puigvert	Barcelona
Spain	University of Barcelona Hospital Clinic	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
United Kingdom	Queen Elizabeth Hospital	Birmingham	West Midlands
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter	Devon
United Kingdom	Queen Elizabeth University Hospital Campus	Glasgow	Strathclyde
United Kingdom	Leicester General Hospital	Leicester	Leicestershire
United Kingdom	Kings College Hospital	London
United Kingdom	Salford Royal NHS Foundation Trust	Salford	Greater Manchester
United States	DaVita Clinical Research	Asheville	North Carolina
United States	Fresenius Kidney Care	Bethlehem	Pennsylvania
United States	Boca Nephrology, PA	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	DaVita Clinical Research	Bronx	New York
United States	Fresenius Kidney Care	Brookhaven	Mississippi
United States	DaVita Clinical Research	Chesapeake	Virginia
United States	DaVita Clinical Research	Chester	Pennsylvania
United States	Fresenius Kidney Care	Columbia	South Carolina
United States	Hypertension Nephrology Consultants, Inc	Columbus	Ohio
United States	Colorado Kidney Care	Denver	Colorado
United States	Fresenius Kidney Care	Durham	North Carolina
United States	California Institute of Renal Research	El Centro	California
United States	California Institute of Renal Research	Escondido	California
United States	Kidney Disease Medical Group	Glendale	California
United States	DaVita Clinical Research	Hollywood	Florida
United States	DaVita Clinical Research	Houston	Texas
United States	DaVita Clinical Research	Kansas City	Missouri
United States	Knoxville Kidney Center	Knoxville	Tennessee
United States	DaVita Clinical Research	Las Vegas	Nevada
United States	DaVita Clinical Research	Lynwood	California
United States	DaVita Clinical Research	Minneapolis	Minnesota
United States	DaVita Clinical Research	Norfolk	Virginia
United States	AKDHC Medical Research Services	Phoenix	Arizona
United States	Michigan Kidney Consultants	Pontiac	Michigan
United States	Fresenius Kidney Care	Reno	Nevada
United States	Apex Research of Riverside	Riverside	California
United States	Fresenius Kidney Care	Roanoke	Virginia
United States	DaVita Clinical Research	Roseville	Michigan
United States	Clinical Advancement Center	San Antonio	Texas
United States	Fresenius Kidney Care	San Diego	California
United States	North America Research Institute	San Dimas	California
United States	Novel Outcomes Research	Spring Hill	Florida
United States	DaVita Clinical Research	Tampa	Florida
United States	Fresenius Kidney Care	Tampa	Florida
United States	Amicis Research Center	Vacaville	California
United States	DaVita Clinical Research	Wauwatosa	Wisconsin
United States	Piedmont Dialysis Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanifit Therapeutics S. A.

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Qualitative Wound Image Evaluation for the Primary Lesion	A qualitative assessment (Worsened, Equal to, or Improved Relative to Baseline) was assigned	at Week 12
Secondary	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