Clinical trial NCT02966028: Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD)
Official title: A Double-blind, Randomised, Placebo-controlled Study to Assess the Effect of SNF472 on Progression of Cardiovascular Calcification on Top of Standard of Care in End-stage-renal-disease (ESRD) Patients on Hemodialysis (HD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Diseases
Cardiovascular Abnormalities
Calcifications, Vascular
Endstage Renal Disease
ESRD
Coronary Artery Calcification
Keywords: CAC
calcium
ESRD
calcification
cardiovascular
heart
kidney
hemodialysis
Agatston
Lead sponsor: Sanifit Therapeutics S. A.
Sponsor class: OTHER
Collaborators: name: Clinipace Worldwide
First posted: 2016-11-17
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to assess the effect of 2 dose levels of SNF472 (300 mg and 600 mg) compared to placebo on the progression of coronary artery calcium volume score over a 12-month (52 weeks) period in ESRD patients on HD

Detailed description: Reducing the progression of cardiovascular calcification (CVC) in HD patients may improve the severe burden of CV disease related to the underlying ESRD. As no therapy is currently indicated to target CVC, there is a need to investigate the ability of SNF472 to reduce CVC progression and, ultimately, to improve CV outcomes in HD patients. This phase 2b double-blind, randomised, placebo-controlled study is designed to assess the effect of SNF472 on the progression of CVC as measured by calcium volume and CAC/Agatston scores in ESRD patients receiving HD. The study hypothesis is that administration of SNF472 over 52 weeks can slow the progression of CVC in this patient population compared to placebo.

Eligibility criteria: Inclusion Criteria:

* Female or male patients, 18 to 80 years (inclusive) of age at randomisation
* CAC score of 100 to 3500 AU (Agatston Units) inclusive within a 3-week period prior to randomisation as measured by a multi-detector CT scanner
* Patients who are EITHER ≥ 55 years OR have a history of diabetes mellitus at randomisation
* Patients on HD for ≥ 6 months prior to randomisation
* Willing and able to understand and sign the informed consent

Exclusion Criteria:

* Scheduled date for kidney transplant from a known living donor
* Weight above 300 lbs (136 kg)
* Hospitalisation in the previous 3 months prior to randomisation for unstable angina, MI, stroke, transient ischaemic attack, amputation or peripheral or coronary bypass surgery
* History of unstable heart failure in the previous 3 months, defined as an unplanned presentation to a hospital or dialysis treatment facility with signs/symptoms of acute pulmonary edema and requiring ultrafiltration therapy
* History of cancer that has been in remission for \< 5 years prior to randomisation. A history of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin is allowed
* Pregnant or trying to become pregnant, currently breast-feeding, or of child-bearing potential (including peri-menopausal women who have had a menstrual period within one year) and not willing to practice birth control using a double barrier method (criteria apply to women only) at least 30 days post last dose of study medication
* Hypocalcaemia defined as a serum calcium below 8.0 mg/dL (or 2.0 mmol/L) for the serum calcium most proximal to screening per patient's medical records
* Extreme elevation in serum phosphorous, defined as a serum phosphorous above 10 mg/dL (or 3.23 mmol/L) within the last 2 months proximal to screening per patient's medical records
* Uncontrolled hypertension defined as any 2 or more consecutive post-dialysis diastolic blood pressure (DBP) \> 100 mmHg within the last 2 months proximal to screening expected survival \< 2 years in the Investigator's medical opinion
* Known active drug or alcohol abuse within 1 year of randomisation
* Use of other investigational drugs within 30 days of randomisation
* Non-compliance with dialysis treatment which, in the opinion of the Investigator, evidenced by either repeated missed dialysis treatments or significant non-compliance with the patient's medication regimen
* Inability to comply with all required study procedures and schedule, inability to speak and read in the protocol-derived language of that patient's clinical site, or unwillingness or inability to give written informed consent

Primary outcomes:
measure: Change in Log CAC Volume Score From Baseline to Week 52 for the Combined Dose Groups vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
Secondary outcomes:
measure: Change in Log CAC Volume Score From Baseline to Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Change in Log CAC Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and for the Combined Dose Groups vs the Placebo Group
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Number of Subjects With <15% Progression in CAC Agatston Score From Baseline to Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Number of Subjects With >=15% Progression in CAC Agatston Score at Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Change in Log Thoracic Aorta Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Change in Log Thoracic Aorta Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Change in Log Aortic Valve Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Change in Log Aortic Valve Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Number of Participants With the Composite Safety Endpoint (Cardiovascular Death, Nonfatal Myocardial Infarction, Non-fatal Stroke, Heart Failure or Non-fatal Cardiac Arrest.
timeFrame: Baseline (Week 1, Day 1) and Week 52
measure: Mortality Rate (All-cause) for Each Dose Group and Placebo
timeFrame: Baseline (Week 1, Day 1) and Week 52
Other outcomes:
Locations:
city: Bakersfield
country: United States
state: California
city: Chula Vista
country: United States
state: California
city: Escondido
country: United States
state: California
city: Granada Hills
country: United States
state: California
city: La Palma
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Lynwood
country: United States
state: California
city: Northridge
country: United States
state: California
city: Riverside
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Dimas
country: United States
state: California
city: Simi Valley
country: United States
state: California
city: Tarzana
country: United States
state: California
city: Whittier
country: United States
state: California
city: Arvada
country: United States
state: Colorado
city: Westminster
country: United States
state: Colorado
city: Middlebury
country: United States
state: Connecticut
city: Orange
country: United States
state: Connecticut
city: Hollywood
country: United States
state: Florida
city: Lauderdale Lakes
country: United States
state: Florida
city: Miami Gardens
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Evanston
country: United States
state: Illinois
city: Shreveport
country: United States
state: Louisiana
city: Pontiac
country: United States
state: Michigan
city: Roseville
country: United States
state: Michigan
city: Brookhaven
country: United States
state: Mississippi
city: Las Vegas
country: United States
state: Nevada
city: Reno
country: United States
state: Nevada
city: North Brunswick
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: College Point
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Bethlehem
country: United States
state: Pennsylvania
city: Knoxville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Richardson
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Chesapeake
country: United States
state: Virginia
city: Wauwatosa
country: United States
state: Wisconsin
city: Palma de Mallorca
country: Spain
state: Balearic Islands
city: Barcelona
country: Spain
state: Catalonia
city: Palma
country: Spain
state: Illes Balears
city: Palma
country: Spain
state: Islas Baleares
city: Galdakao
country: Spain
state: Vizcaya
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Córdoba
country: Spain
city: Lleida
country: Spain
city: Lleida
country: Spain
city: Lugo
country: Spain
city: Madrid
country: Spain
city: Navarro
country: Spain
city: Oviedo
country: Spain
city: Palma
country: Spain
city: Santander
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Bradford
country: United Kingdom
city: Manchester
country: United Kingdom
city: Salford
country: United Kingdom
city: Shrewsbury
country: United Kingdom
city: Swansea
country: United Kingdom
city: Westcliff-on-Sea
country: United Kingdom
Study officials:
affiliation: Sanifit Chief Medical Officer
name: Alex Gold, MD
role: STUDY_DIRECTOR
References:
citation: Bushinsky DA, Raggi P, Bover J, Ketteler M, Bellasi A, Rodriguez M, Sinha S, Garg R, Perello J, Gold A, Chertow GM; CaLIPSO Investigators*; CaLIPSO Study Group and Clinipace GmbH, Intrinsic Imaging, LLC. Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study. Clin J Am Soc Nephrol. 2021 May 8;16(5):736-745. doi: 10.2215/CJN.16931020. Epub 2021 Apr 7.
citation: Raggi P, Bellasi A, Bushinsky D, Bover J, Rodriguez M, Ketteler M, Sinha S, Salcedo C, Gillotti K, Padgett C, Garg R, Gold A, Perello J, Chertow GM. Slowing Progression of Cardiovascular Calcification With SNF472 in Patients on Hemodialysis: Results of a Randomized Phase 2b Study. Circulation. 2020 Mar 3;141(9):728-739. doi: 10.1161/CIRCULATIONAHA.119.044195. Epub 2019 Nov 11.