Kliniske forsøg Nct side

Summary
EudraCT Number:2022-002924-11
Sponsor's Protocol Code Number:LOLAbiome
National Competent Authority:Austria - BASG
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2023-01-26
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedAustria - BASG
A.2EudraCT number2022-002924-11
A.3Full title of the trial
An observational study on the effect of L-ornithine-L-aspertate (LOLA) on the Flavonifractor abundance in the gut microbiome in liver cirrhosis
Eine Beobachtungsstudie zur Wirkung von L-Ornithin- L- Aspartat (LOLA) auf das Vorkommen von Flavonifractor im Darmmikrobiom bei Leberzirrhose
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Study to test the effect of the drug "L-ornithine.L-aspertate" (LOLA) on microorganisms in the digestive tract in patients with liver cirrhosis (damage of the liver due to liver disease)
Eine Beobachtungsstudie zur Wirkung von L-Ornithin-L-Aspartat (LOLA) auf die Darmflora von Patienten mit Leberzirrhose (Schädigung der Leber aufgrund einer Lebererkrankung)
A.3.2Name or abbreviated title of the trial where available
LOLAbiome
A.4.1Sponsor's protocol code numberLOLAbiome
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorCBmed GmbH
B.1.3.4CountryAustria
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing support
B.4.2Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationCBmed
B.5.2Functional name of contact pointClinical Trial Information
B.5.3 Address:
B.5.3.1Street AddressStiftingtalstraße 5
B.5.3.2Town/ cityGraz
B.5.3.3Post code8010
B.5.3.4CountryAustria
B.5.6E-mailangela.horvath@medunigraz.at
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Hepa-Merz-3 g Granulat
D.2.1.1.2Name of the Marketing Authorisation holderMerz Pharma Austria GmbH
D.2.1.2Country which granted the Marketing AuthorisationAustria
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameHepa-Merz 3 g Granulat
D.3.4Pharmaceutical form Granules
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Liver cirrhosis with covert or overt hepatic encephalopathy (grade 0-2)
Leberzirrhose mit subklinischer oder manifester Hepatischer Enzephalopathie (Grad 0-2)
E.1.1.1Medical condition in easily understood language
Late stage liver disease with a related disorder of the brain
Endstadium einer Lebererkrankung und damit verbundene Funktionsstörung des Gehirns
E.1.1.2Therapeutic area Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10024667
E.1.2Term Liver cirrhosis
E.1.2System Organ Class 100000004871
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10014630
E.1.2Term Encephalopathy hepatic
E.1.2System Organ Class 100000004852
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To test whether L-ornithine-L-aspartate (LOLA) alters gut microbiome composition (Flavonifractor) in liver cirrhosis with covert or overt hepatic encephalopathy (Grade 0-2)
Evaluierung, ob L-ornithine-L-aspartate (LOLA) bei Patienten mit Leberzirrhose und einer subklinischen oder manifesten Hepatischen Enzephalopathie (Grad 0-2), zu einer Veränderung der Zusammensetzung des Darmmikrobioms (Flavonifractor) führt
E.2.2Secondary objectives of the trial
To test whether LOLA alters gut microbiome function in liver cirrhosis
To test whether LOLA alters metabolite composition in stool, serum or urine in liver cirrhosis
To test whether LOLA improves gut permeability and inflammation in liver cirrhosis
To test whether LOLA improves elevated ammonia levels in blood
To test whether LOLA improves muscle function in cirrhosis
To test whether LOLA prevents complications of cirrhosis
Evaluierung, ob LOLA bei Patienten mit Leberzirrhose die Funktion des Darmmikkrobioms verändert
Evaluierung, ob LOLA bei Patienten mit Leberzirrhose die Zusammensetzung von Metaboliten im Stuhl, Serum oder Urin verändert
Evaluierung, ob LOLA bei Patienten mit Leberzirrhose die Permeabilität der Darmschleimhaut/Entzündungszustände verbessert
Evaluierung, ob LOLA bei Patienten mit Leberzirrhose zu einer Verbesserung erhöhter Ammoniaklevel im Blut führt
Evaluierung, ob LOLA bei Patienten mit Leberzirrhose die Muskelfunktion verbessert
Evaluierung, ob LOLA bei Patienten mit Leberzirrhose, Leberzirrhose-assoziierten Komplikationen vorbeugen kann
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
•Liver cirrhosis (clinical/radiological/histological diagnosis)
•Indication for LOLA use (covert or over hepatic encephalopathy, Grad 0-2))
•Written informed consent
•Age 18 -100 years
Leberzirrhose (klinische/radiologische/histologische Diagnose)
Indikation zur Einnahme von LOLA (subklinische oder manifeste Hepatische Enzephalopathie, Grad 0-2)
Vorliegende Einwilligungserklärung
Alter 18-100 Jahre
E.4Principal exclusion criteria
•Allergy to LOLA or its constituents, or to medications with a similar chemical structure (oral nutritional supplements are allowed when stable >/= 8 weeks before and during the study)
•Recent (</= 8 weeks) changes of the dose of the lactulose therapy for hepatic encephalopathy
•Rifaximin or any other antibiotic therapy within the past 4 weeks
•Intake of LOLA in the past four weeks before inclusion
•Intake of L-dopamine
•Renal insufficiency with a serum creatinine >3mg/dl
•Hepatocellular carcinoma BCLC D under best supportive care
•Inability to give informed consent
•Pregnancy or breastfeeding
•Participation in another interventional trial within the last 30 days



Allergie auf LOLA oder dessen Bestandteile oder auf Medikamente mit einer ähnlichen chemischen Struktur
Kürzlich (</= 8 Wochen) erfolgte Dosisänderung der Lactulose Therapie
Rifaximin or andere Antibiotikatherapie innerhalb der vergangenen 4 Wochen vor Studieneinschluss
Einnahme von LOLA innehalb der letzten vier Wochen vor Studieneinschluss
Einnahme von L-Dopamin
Renale Insuffizienz (Serumkreatinin >3mg/dl)
Leberzellkarzinom BCLC Stadium D
Unvermögen, eine informierte Einwilligung zu erteilen
Schwangerschaft/Stillen
Teilnahme an einer anderen interventionellen Studie innerhalb der 30 Tage vor Studieneinschluss
E.5 End points
E.5.1Primary end point(s)
Increase of the genus Flavonifractor in the gut microbiome after 3 months of LOLA treatment
Anstieg der Gattung Flavonifractor im Darmmikrobiom nach 3 Monaten LOLA Therapie
E.5.1.1Timepoint(s) of evaluation of this end point
3 months
3 Monate
E.5.2Secondary end point(s)
Change in alpha diversity of the gut microbiome after 3 months of LOLA treatment
Change in beta diversity of the gut microbiome after 3 months of LOLA treatment
Change in taxonomic composition (beyond Flavonifractor) of the gut microbiome after 3 months of LOLA treatment
Change in predicted gut microbiome function after 3 months of LOLA treatment
Change in stool, serum or urine metabolite composition after 3 months of LOLA treatment
Change in biomarkers of gut permeability after 3 months of LOLA treatment
Change in handgrip strength after 3 months of LOLA treatment
Change in gait speed and balance after 3 months of LOLA treatment
Change in ammonia blood levels after 3 months of LOLA treatment
Change in anthropometric parameters (Mid-arm circumference and triceps fold thickness) after 3 months of LOLA treatment
Change in quality of life after 3 months of LOLA treatment
Occurrence of complications of cirrhosis during the study period
Occurrence of side effects during the study period
Veränderung der alpha Diversität des Darmmikrobioms
Veränderung der beta Diversität des Darmmikrobioms
Veränderung der taxonomischen Zusammensetzung des Darmmikrobioms
Veränderung der vorhergesagten Funktion des Darmmikrobioms
Änderung der Metaboliten-Zusammensetzung in Stuhl, Serum, Urin
Veränderung von Biomarkern zur Permeabilität der Darmschleimhaut
Veränderung der Greifkraft
Veränderung der Gehgeschwindigkeit und Balance
Veränderung des Ammoniakspiegels im Blut
Veränderung von anthropometrischen Parametern
Änderung der Lebensqualität
Auftreten von Leberzirrhose assoziierten Komplikationen im Verlauf der Studie
Auftreten von Nebenwirkungen während der Studie
E.5.2.1Timepoint(s) of evaluation of this end point
3 months
3 Monate
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) Yes
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.3 The trial involves single site in the Member State concerned Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Last visit of the last subject
Letzter Besuch des letzten Patienten
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years2
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years2
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 44
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 11
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state55
F.4.2 For a multinational trial
F.4.2.1In the EEA 55
F.4.2.2In the whole clinical trial 55
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
According to local routine
Gemäß des lokalen Routinevorgehens
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-01-09
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-12-09
P. End of Trial
P.End of Trial StatusOngoing

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