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

NCT04119843 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ASC-Man-P01611-3429
• Study Type: interventional
• Target: 87
• Locations: 10 countries
• Sites: 60

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.

Conditions

Known or Suspected Focal Liver Lesions; Severe Renal Impairment

Outcome Measures

Primary Outcomes (2)

• Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI

  Visualization of focal liver lesions was measured by 2 co-primary variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion border delineation from 1 (poor: lesion border is poorly distinct) to 4 (excellent: lesion border is sharply and clearly distinct). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.

  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

• Co-primary Endpoint: Lesion Contrast in Combined MRI Compared to Unenhanced MRI

  Visualization of focal liver lesions was measured by 2 co-primary variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion contrast from 1 (poor: difference in signal intensity between the lesion and the surrounding normal liver tissue is poor) to 4 (excellent: difference in signal intensity between the lesion and the surrounding liver is marked). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.

  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 (11)

• Number of Lesions Detected by Each MRI Method

  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

• Lesion Border Delineation in Mangoral-enhanced MRI Compared to Unenhanced MRI

  Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

• Lesion Contrast in Mangoral-enhanced MRI Compared to Unenhanced MRI

  Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

• Confidence in Lesion Detection Score

  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

• Confidence in Lesion Localization Score

  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

Study Arms (1)

Mangoral

EXPERIMENTAL

All participants will receive a single dose of Mangoral (800 mg Manganese (II) chloride tetrahydrate \[MnCl2 4H2O\]).

Drug: Mangoral

Interventions

Mangoral DRUG

800 mg manganese chloride \[II\] tetrahydrate, 500 mg L-alanine, and 800 IU vitamin D3

Also known as: Orviglance, CMC-001, ACE-MBCA

Mangoral

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ascelia Pharma AB: lead

Study Sites (60)

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California at Los Angeles Ronald Reagan Medical Center

Los Angeles, California, 90095, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Schiff Center for Liver Diseases

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

Saint Louis University

St Louis, Missouri, 63103, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

PanAmerican Clinical Research LLC

Brownsville, Texas, 78521, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

Fundación Intecnus

Bariloche, Río Negro Province, R8405AZA, Argentina

Location

Centro Rossi Body Imaging

Buenos Aires, C1425 BEE, Argentina

Location

Sanatorio Allende Nueva Córdoba

Córdoba, X5000JHQ, Argentina

Location

Hospital Pablo Tobon Uribe

Medellín, Antioquia, 69-240, Colombia

Location

Clínica Universitaria Colombia

Bogotá, Cundinamarca, 111221, Colombia

Location

Sociedad de Cirugía de Bogotá - Hospital de San José

Bogotá, Cundinamarca, 111611, Colombia

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Frankfurt Institut für Diagnostische und Interventionelle Radiologie

Frankfurt, 60590, Germany

Location

Universitätsmedizin Göttingen

Göttingen, Germany

Location

Städtisches Klinikum KarlsruheDiagnostische und interventionelle Radiologie

Karlsruhe, 76227, Germany

Location

Universitättsklinikum Schleswig-Holstein/Campus KielKlinik für Radiologie und Neuroradiologie

Kiel, 24105, Germany

Location

Klinik und Poliklinik für Radiologie Klinikum der Universität München LMU Campus

Munich, 81377, Germany

Location

Institut für Röntgendiagnostik

Regensburg, 93053, Germany

Location

Azienda Socio Sanitaria Territoriale (ASST)

Milan, Lombardy, 20157, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Ospedale del Mare

Napoli, 80147, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, Italy

Location

Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico Umberto I

Rome, 00161, Italy

Location

Ospedale di Belcolle

Viterbo, 01100, Italy

Location

Panamerican Clinical Research - Cuernavaca Rio Mayo

Cuernavaca, 62290, Mexico

Location

Panamerican Clinical Research Mexico

Guadalajara, 44670, Mexico

Location

Panamerican Clinical Research - Querétaro Avenida Paseo de la República

Querétaro, 76230, Mexico

Location

Szpital Uniwersytecki nr 1 im. Dr A. Jurasza, Wydział Katedra i Zakład Radiologii i Diagnostyki Obrazowej

Bydgoszcz, Poland

Location

Szpital Uniwersytecki w Krakowie Zakład Diagnostyki Obrazowej CUMRiK Ul

Krakow, 31-501, Poland

Location

EuroMedis Sp. z o.o.

Szczecin, 70-111, Poland

Location

Altay Regional Oncology Dispencery

Barnaul, Zmeigorsky trakt 110, Russia

Location

State Institution of Healthcare "Regional Oncology Dispensary"

Irkutsk, 664035, Russia

Location

Scientific and Research Institute of Oncology named after N.N. Blokhin

Moscow, 115478, Russia

Location

A.V. Vishnevsky Institute of Surgery

Moscow, 117997, Russia

Location

National Medical Research Radiology Center Named After Herzen

Moscow, 125284, Russia

Location

JSC "Avicenna"

Novosibirsk, 630099, Russia

Location

State Institution of Healthcare of Omsk region

Omsk, 644013, Russia

Location

SBIH of Pskov Regional Clinical Oncologic Dispensary

Pskov, 180004, Russia

Location

LLC "Clinica YZI 4D"

Pyatigorsk, 357500, Russia

Location

N.N. Petrov Research Institute of Oncology

Saint Petersburg, 197758, Russia

Location

Saint-Petersburg State Budgetary Healthcare Institution

Saint Petersburg, 198255, Russia

Location

Smolensk Clinical Hospital

Smolensk, 214006, Russia

Location

State Autonomous Healthcare Institution of the Tyumen Region

Tyumen, 625033, Russia

Location

Karolinska University Hospital Huddinge

Stockholm, Sweden

Location

Ege University Medical Faculty Hospital

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Erciyes University Medical Faculty Hospital

Melikgazi, Kayseri, 38030, Turkey (Türkiye)

Location

Kocaeli University

İzmit, Kocaeli, 41001, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty Hospital

Ankara, 06230, Turkey (Türkiye)

Location

İstanbul Üniversitesi - Istanbul Tıp Fakültesi

Istanbul, 34093, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

CMC-001

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Andreas Norlin
• Organization: Ascelia Pharma AB

an@ascelia.com

+46 735179119

Study Officials

• Bernd Hamm, MD

  Charite Berlin, Dept. of Radiology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, open-label, pivotal phase III study

Study Record Dates

• First Submitted: September 29, 2019
• First Posted: October 8, 2019
• Study Start: February 19, 2020
• Primary Completion: February 17, 2023
• Study Completion: February 17, 2023
• Last Updated: February 6, 2025
• Results First Posted: February 6, 2025

Record last verified: 2025-01

Locations

CO (3); US (14); DE (7); IT (8); ME (3); PL (3); TU (5); AR (3); RU (13); SE (1)