Clinical trial NCT04119843: Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function
Official title: A Multicenter, Open-label Study to Evaluate the Safety and Diagnostic Efficacy of Mangoral in Patients With Known or Suspected Focal Liver Lesions and Severe Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Known or Suspected Focal Liver Lesions
Severe Renal Impairment
Lead sponsor: Ascelia Pharma AB
Sponsor class: INDUSTRY
First posted: 2019-10-08
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multicenter, open-label, pivotal phase III study
Primary purpose: DIAGNOSTIC

Brief summary: The overall objective of this study is to evaluate the safety and diagnostic efficacy of Mangoral in liver MRI in participants with known or suspected focal liver lesions and severe renal impairment. The diagnostic efficacy of Mangoral will be assessed in terms of visualization of detected focal liver lesions in combined MRI (CMRI: combined Mangoral-enhanced and unenhanced MRI) compared to unenhanced MRI.

Detailed description: The overall objective of this multicenter, open-label, study is to evaluate the safety and diagnostic efficacy of Mangoral in participants with known or suspected focal liver lesions and severe renal impairment. Study treatment is a single oral dose of Mangoral (800 mg manganese chloride \[II\] tetrahydrate, 500 mg L-alanine, and 800 IU vitamin D3). Adult male and female participants with severe renal impairment or acute kidney injury and who are being evaluated for known or suspected focal liver lesions will be included. Primary diagnostic efficacy in terms of visualization of detected lesions will be evaluated centrally by 3 independent readers. Study MRIs will also be evaluated by the on-site radiologists for the assessment of secondary objectives and for clinical purposes.

Eligibility criteria: Inclusion Criteria:

* Male and female participants 18 years and older.
* Known or suspected focal liver lesions based on medical history and previous laboratory and/or imaging examinations.
* Severe renal impairment (estimated glomerular filtration rate \[eGFR\] \< 30 mL/min/1.73 m\^2) based on medical history and previous laboratory examinations, at least once, within the last 3 months prior to the Baseline Visit, or participants with an increase in serum creatinine ≥ 0.3 mg/dL within 48 hours or ≥ 50% within 7 days prior to the Baseline Visit.

Exclusion Criteria:

* Participants with simple liver cysts only.
* Any investigational drug or device within 6 weeks prior to the Baseline Visit.
* Any magnetic resonance imaging (MRI) contrast media within 6 weeks prior to Baseline Visit or scheduled to receive any contrast medium before the last study visit.
* Participants with severe hepatic impairment (according to Child-Pugh score C).
* Participants scheduled for surgery before last study visit.
* Participants with encephalopathy / neurodegenerative or acute neurological disorders.
* Participants with hemochromatosis.

Primary outcomes:
measure: Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
measure: Co-primary Endpoint: Lesion Contrast in Combined MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
Secondary outcomes:
measure: Number of Lesions Detected by Each MRI Method
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
measure: Lesion Border Delineation in Mangoral-enhanced MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0
measure: Lesion Contrast in Mangoral-enhanced MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0
measure: Confidence in Lesion Detection Score
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
measure: Confidence in Lesion Localization Score
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
measure: Longest Diameter of Largest and Smallest Lesion
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0
measure: Percentage Liver Signal Intensity (SI) Enhancement in Mangoral-enhanced MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0
measure: Liver-to-lesion Contrast (LLC) in Mangoral-enhanced MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0
measure: Signal-to-noise Ratio (SNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0
measure: Contrast-to-noise Ratio (CNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0
measure: Number of Participants With Change(s) in Recommended Management Based on Diagnostic Performance of Combined MRI or Mangoral-enhanced MRI Compared to Unenhanced MRI
timeFrame: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of California at Los Angeles Ronald Reagan Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Brownsville
country: United States
facility: PanAmerican Clinical Research LLC
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: San Carlos De Bariloche
country: Argentina
facility: Fundación Intecnus
state: Río Negro
city: Buenos Aires
country: Argentina
facility: Centro Rossi Body Imaging
city: Cordoba
country: Argentina
facility: Sanatorio Allende Nueva Córdoba
city: Medellín
country: Colombia
facility: Hospital Pablo Tobon Uribe
state: Antioquia
city: Bogotá
country: Colombia
facility: Clínica Universitaria Colombia
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Sociedad de Cirugía de Bogotá - Hospital de San José
state: Cundinamarca
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt Institut für Diagnostische und Interventionelle Radiologie
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum KarlsruheDiagnostische und interventionelle Radiologie
city: Kiel
country: Germany
facility: Universitättsklinikum Schleswig-Holstein/Campus KielKlinik für Radiologie und Neuroradiologie
city: Munich
country: Germany
facility: Klinik und Poliklinik für Radiologie Klinikum der Universität München LMU Campus
city: Regensburg
country: Germany
facility: Institut für Röntgendiagnostik
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale (ASST)
state: Lombardy
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola-Malpighi
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Ospedale del Mare
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Umberto I
city: Viterbo
country: Italy
facility: Ospedale di Belcolle
city: Cuernavaca
country: Mexico
facility: Panamerican Clinical Research - Cuernavaca Rio Mayo
city: Guadalajara
country: Mexico
facility: Panamerican Clinical Research Mexico
city: Querétaro
country: Mexico
facility: Panamerican Clinical Research - Querétaro Avenida Paseo de la República
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. Dr A. Jurasza, Wydział Katedra i Zakład Radiologii i Diagnostyki Obrazowej
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie Zakład Diagnostyki Obrazowej CUMRiK Ul
city: Szczecin
country: Poland
facility: EuroMedis Sp. z o.o.
city: Barnaul
country: Russian Federation
facility: Altay Regional Oncology Dispencery
city: Irkutsk
country: Russian Federation
facility: State Institution of Healthcare "Regional Oncology Dispensary"
city: Moscow
country: Russian Federation
facility: Scientific and Research Institute of Oncology named after N.N. Blokhin
city: Moscow
country: Russian Federation
facility: A.V. Vishnevsky Institute of Surgery
city: Moscow
country: Russian Federation
facility: National Medical Research Radiology Center Named After Herzen
city: Novosibirsk
country: Russian Federation
facility: JSC "Avicenna"
city: Omsk
country: Russian Federation
facility: State Institution of Healthcare of Omsk region
city: Pskov
country: Russian Federation
facility: SBIH of Pskov Regional Clinical Oncologic Dispensary
city: Pyatigorsk
country: Russian Federation
facility: LLC "Clinica YZI 4D"
city: Saint Petersburg
country: Russian Federation
facility: N.N. Petrov Research Institute of Oncology
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Healthcare Institution
city: Smolensk
country: Russian Federation
facility: Smolensk Clinical Hospital
city: Tyumen
country: Russian Federation
facility: State Autonomous Healthcare Institution of the Tyumen Region
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Bornova
country: Turkey
facility: Ege University Medical Faculty Hospital
state: İzmir
city: Melikgazi
country: Turkey
facility: Erciyes University Medical Faculty Hospital
state: Kayseri
city: İzmit
country: Turkey
facility: Kocaeli University
state: Kocaeli
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty Hospital
city: Istanbul
country: Turkey
facility: İstanbul Üniversitesi - Istanbul Tıp Fakültesi
Study officials:
affiliation: Charite Berlin, Dept. of Radiology
name: Bernd Hamm, MD
role: PRINCIPAL_INVESTIGATOR
References: