Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function (SPARKLE)

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

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.

Study Overview

• Status: Completed
• Conditions: Severe Renal Impairment; Known or Suspected Focal Liver Lesions
• Intervention / Treatment: Drug: Mangoral

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.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Karin Liljeberg; Phone Number: +46 735 179 112; Email: sparkle@ascelia.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425 BEE
    • Centro Rossi Body Imaging
  • Cordoba, Argentina, X5000JHQ
    • Sanatorio Allende Nueva Córdoba
  • Río Negro
    • San Carlos De Bariloche, Río Negro, Argentina, R8405AZA
      • Fundacion Intecnus
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 69-240
      • Hospital Pablo Tobon Uribe
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia, 111221
      • Clínica Universitaria Colombia
    • Bogotá, Cundinamarca, Colombia, 111611
      • Sociedad de Cirugía de Bogotá - Hospital de San José
• Germany
  • Berlin, Germany
    • Charité - Universitätsmedizin Berlin
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt Institut für Diagnostische und Interventionelle Radiologie
  • Göttingen, Germany
    • Universitätsmedizin Göttingen
  • Karlsruhe, Germany, 76227
    • Städtisches Klinikum KarlsruheDiagnostische und interventionelle Radiologie
  • Kiel, Germany, 24105
    • Universitättsklinikum Schleswig-Holstein/Campus KielKlinik für Radiologie und Neuroradiologie
  • Munich, Germany, 81377
    • Klinik und Poliklinik für Radiologie Klinikum der Universität München LMU Campus
  • Regensburg, Germany, 93053
    • Institut für Röntgendiagnostik
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola-Malpighi
  • Milano, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Napoli, Italy, 80147
    • Ospedale del Mare
  • Napoli, Italy
    • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
  • Roma, Italy, 00168
    • Universita Cattolica del Sacro Cuore
  • Rome, Italy, 00161
    • Azienda Ospedaliero-Universitaria Policlinico Umberto I
  • Viterbo, Italy, 01100
    • Ospedale di Belcolle
  • Lombardy
    • Milano, Lombardy, Italy, 20157
      • Azienda Socio Sanitaria Territoriale (ASST)
• Mexico
  • Cuernavaca, Mexico, 62290
    • Panamerican Clinical Research - Cuernavaca Rio Mayo
  • Guadalajara, Mexico, 44670
    • Panamerican Clinical Research Mexico
  • Querétaro, Mexico, 76230
    • Panamerican Clinical Research - Querétaro Avenida Paseo de la República
• Poland
  • Bydgoszcz, Poland
    • Szpital Uniwersytecki nr 1 im. Dr A. Jurasza, Wydział Katedra i Zakład Radiologii i Diagnostyki Obrazowej
  • Kraków, Poland, 31-501
    • Szpital Uniwersytecki w Krakowie Zakład Diagnostyki Obrazowej CUMRiK Ul
  • Szczecin, Poland, 70-111
    • EUROMEDIS Sp. z o.o.
• Russian Federation
  • Barnaul, Russian Federation, Zmeigorsky trakt 110
    • Altay Regional Oncology Dispencery
  • Irkutsk, Russian Federation, 664035
    • State Institution of Healthcare "Regional Oncology Dispensary"
  • Moscow, Russian Federation, 115478
    • Scientific and Research Institute of Oncology named after N.N. Blokhin
  • Moscow, Russian Federation, 117997
    • A.V. Vishnevsky Institute of Surgery
  • Moscow, Russian Federation, 125284
    • National Medical Research Radiology Center Named After Herzen
  • Novosibirsk, Russian Federation, 630099
    • JSC "Avicenna"
  • Omsk, Russian Federation, 644013
    • State Institution of Healthcare of Omsk region
  • Pskov, Russian Federation, 180004
    • SBIH of Pskov Regional Clinical Oncologic Dispensary
  • Pyatigorsk, Russian Federation, 357500
    • LLC "Clinica YZI 4D"
  • Saint Petersburg, Russian Federation, 197758
    • N.N. Petrov Research Institute of Oncology
  • Saint Petersburg, Russian Federation, 198255
    • Saint-Petersburg State Budgetary Healthcare Institution
  • Smolensk, Russian Federation, 214006
    • Smolensk Clinical Hospital
  • Tyumen, Russian Federation, 625033
    • State Autonomous Healthcare Institution of the Tyumen Region
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital Huddinge
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe University Medical Faculty Hospital
  • Istanbul, Turkey, 34093
    • İstanbul Üniversitesi - Istanbul Tıp Fakültesi
  • Kayseri
    • Melikgazi, Kayseri, Turkey, 38030
      • Erciyes University Medical Faculty Hospital
  • Kocaeli
    • İzmit, Kocaeli, Turkey, 41001
      • Kocaeli University
  • İzmir
    • Bornova, İzmir, Turkey, 35100
      • Ege University Medical Faculty Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic - Arizona
  • California
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles Ronald Reagan Medical Center
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Bayview Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63103
      • Saint Louis University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Texas
    • Brownsville, Texas, United States, 78521
      • PanAmerican Clinical Research LLC
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University Of Wisconsin - Madison

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mangoral; All participants will receive a single dose of Mangoral (equivalent to 800 mg Manganese (II) chloride tetrahydrate [MnCl2 4H2O]).	Drug: Mangoral; 800 mg manganese chloride [II] tetrahydrate, 500 mg L-alanine, and 800 IU vitamin D3; Other Names: Orviglance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary efficacy endpoint is the visualization of detected focal liver lesions in combined MRI (CMRI, Mangoral-enhanced MRI plus unenhanced MRI) as compared to unenhanced MRI.	Visualization will be measured by 2 co-primary variables: lesion border delineation and lesion contrast compared to liver background. Central reading sessions by 3 independent readers for all 3 parts (CMRI, Mangoral-enhanced MRI plus unenhanced MRI). There will be a 2-weeks gap between read parts to reduce recall bias.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of lesions detected by each MRI method (unenhanced MRI, Mangoral-enhanced MRI, and CMRI.)	Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination	1 year
Visualization of focal liver lesions in Mangoral-enhanced MRI as compared to unenhanced MRI	Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination	1 year
Confidence in lesion detection separately in unenhanced MRI, Mangoral-enhanced MRI, and CMRI	Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination	1 year
Confidence in lesion localization separately in unenhanced MRI, Mangoral-enhanced MRI, and CMRI	Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination	1 year
Lesion dimensions: longest diameter of largest and smallest lesion	Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination	1 year
Quantitative assessments for up to 5 detected lesions (liver signal intensity enhancement; liver-to-lesion contrast; signal-to-noise ratio; contrast-to-noise Ratio)	Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination	1 year
Change(s) in patients' Management based on diagnostic Performance of CMRI or Mangoral-enhanced MRI vs. unenhanced MRI	Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination	1 year

Collaborators and Investigators

• Sponsor: Ascelia Pharma AB
• Investigators: Principal Investigator: Bernd Hamm, MD, Charite Berlin, Dept. of Radiology

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): February 27, 2023

Study Registration Dates

• First Submitted: September 29, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: ASC-Man-P016; 11-3429 (Other Identifier: FDA Orphan Designation Request)

Drug and device information, study documents

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