Clinical trial • Phase III • Infectious Disease
Amikacin for Mycobacterium xenopi pulmonary infection
Phase III trial of Amikacin for Mycobacterium xenopi pulmonary infection.
Overview
- Trial Therapeutic Area
- Infectious Disease
- Trial Disease
- Mycobacterium xenopi pulmonary infection
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 19-04-2024
- First CTIS Authorization Date
- 15-07-2024
Trial design
Randomised, open-label, two arms: bras 1 — rifampicin + ethambutol + clarithromycin with arikayce® (arikayce liposomal 590 mg nebuliser dispersion). arikayce: 590 mg inhalation (product listed as 'arikayce liposomal 590 mg nebuliser dispersion', maxdailydoseamount 590 mg, maxtreatmentperiod 6 months). bras 2 — rifampicin + ethambutol + clarithromycin without arikayce®. rifampicin (oral) listed with maxdailydoseamount 10 mg/kg; ethambutol (oral) listed maxdailydoseamount 15 mg/kg (maxtotaldoseamount 20 mg/kg); clarithromycin (oral) listed with maxdailydoseamount 1000 mg.-controlled Phase III trial across 33 sites in France.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Two arms: BRAS 1 — rifampicin + ethambutol + clarithromycin with ARIKAYCE® (ARIKAYCE liposomal 590 mg nebuliser dispersion). ARIKAYCE: 590 mg inhalation (product listed as 'ARIKAYCE liposomal 590 mg nebuliser dispersion', maxDailyDoseAmount 590 mg, maxTreatmentPeriod 6 months). BRAS 2 — rifampicin + ethambutol + clarithromycin without ARIKAYCE®. Rifampicin (oral) listed with maxDailyDoseAmount 10 mg/kg; Ethambutol (oral) listed maxDailyDoseAmount 15 mg/kg (maxTotalDoseAmount 20 mg/kg); Clarithromycin (oral) listed with maxDailyDoseAmount 1000 mg.
- Target Sample Size
- 190
- Trial Duration For Participant
- 730
Eligibility
Recruits 190 No vulnerable populations selected (isVulnerablePopulationSelected:false). Trial population restricted to adults (18 years or older). Informed consent via adult subject information sheet and informed consent form (L1_SIS and ICF Adults) is provided; no assent process for minors as they are excluded..
- Pregnancy Exclusion
- Pregnancy and breastfeeding
- Vulnerable Population
- No vulnerable populations selected (isVulnerablePopulationSelected:false). Trial population restricted to adults (18 years or older). Informed consent via adult subject information sheet and informed consent form (L1_SIS and ICF Adults) is provided; no assent process for minors as they are excluded.
Inclusion criteria
- {"criterion_text":"- 18 years old or older, must present 2020 ATS/ERS/ESCMID/IDSA criteria for nontuberculous mycobacterial pulmonary infection\n- Clinical criteria Respiratory symptoms and the presence of nodular or cavitary lesion on chest x-ray, confirmed on chest high-resolution computed tomography. Lesions may also present in the form of diffuse micronodular syndrome.\n- Microbiological criteria: o At least two positive cultures for MX on two sputum specimens obtained on two different days, at least separate of 7 days AND/OR o Positive culture for MX on bronchoalveolar lavage or bronchoscopic aspiration AND/OR o Transbronchial biopsy or surgical lung biopsy presenting histology in favour of mycobacterial infection (granuloma or positive Ziehl-Neelsen stain) and positive culture for MX OR biopsy showing histology compatible with mycobacterial infection and one or more sputum cultures positive for MX\n- Exclusion of other diagnoses on CT scan, bronchoscopy and bacteriological specimens."}
Exclusion criteria
- {"criterion_text":"- Known hypersensitivity to one of the molecules of the study\n- Relapse of MX lung infection\n- Treatment with molecules able to interfere with cytochrome P450 that cannot be replaced by another therapeutic class\n- HIV 1 and 2 human immunodeficiency virus infection\n- Renal failure with creatinine clearance less than 30 mL/min\n- Pregnancy and breastfeeding\n- Cystic fibrosis\n- Contraindications to one of the antibiotic\n- Inability to comply with the requirements of the protocol, especially substance abuse, according to the investigator.\n- Limited life expectancy (e.g 36 months)\n- Patients with hematologic malignancies and allogeneic haematopoietic stem cells\n- Women of childbearing age and not using an effective method of contraception (Pearl Index <1%)\n- The patient is treated with molecules prolonging the QT interval that cannot be replaced by another therapeutic class.\n- The patient presents a heart failure with left ventricular ejection fraction less than 30%."}
Endpoints
Primary endpoints
- {"endpoint_text":"- 3 months sputum conversion rate","definition_or_measurement_approach":"Measured as sputum culture negativity at 3 months (endpoint described as 'taux de négativation après 3 mois de traitement')."}
Secondary endpoints
- {"endpoint_text":"- 6 months sputum conversion rate, recurrence, failure, relapse, cure, death and safety","definition_or_measurement_approach":"Includes culture conversion at 6 months and clinical outcomes (recurrence, failure, relapse, cure, death) and safety assessments; secondary objectives also list time to culture conversion and 12- and 24-month mortality/microbiological and clinical cure outcomes."}
Recruitment
- Planned Sample Size
- 190
- Recruitment Window Months
- 68
- Consent Approach
- Informed consent obtained from adult participants using subject information sheet and informed consent form for adults (L1_SIS and ICF Adults). Documents for adult consent included in submission; materials available in French (protocol synopsis and translations present). No assent procedures for minors (minors excluded).
Geography
- Total Number Of Sites
- 33
- Total Number Of Participants
- 190
France
- Earliest CTIS Part Ii Submission Date
- 13-05-2024
- Latest Decision Or Authorization Date
- 24-10-2025
- Processing Time Days
- 529
- Number Of Sites
- 33
- Number Of Participants
- 190
Sites
- Site Name
- Centre Hospitalier De Perpignan
- Department Name
- Pneumology
- Principal Investigator Name
- Léa COLOMBAIN
- Principal Investigator Email
- lea.colombain@ch-perpignan.fr
- Contact Person Name
- Léa COLOMBAIN
- Contact Person Email
- lea.colombain@ch-perpignan.fr
- Site Name
- Assistance Publique Hopitaux De Marseille
- Department Name
- Pneumology
- Principal Investigator Name
- Martine REYNAUD-GAUBERT
- Principal Investigator Email
- MartineLouise.REYNAUD@ap-hm.fr
- Contact Person Name
- Martine REYNAUD-GAUBERT
- Contact Person Email
- MartineLouise.REYNAUD@ap-hm.fr
- Site Name
- Centre Hospitalier D'Abbeville
- Department Name
- Pneumology
- Principal Investigator Name
- Estelle HOGUET
- Principal Investigator Email
- hoguet.estelle@ch-abbeville.fr
- Contact Person Name
- Estelle HOGUET
- Contact Person Email
- hoguet.estelle@ch-abbeville.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Pneumology
- Principal Investigator Name
- Loic KASSEGNE
- Principal Investigator Email
- loic.kassegne@chru-strasbourg.fr
- Contact Person Name
- Loic KASSEGNE
- Contact Person Email
- loic.kassegne@chru-strasbourg.fr
- Site Name
- Centre Hospitalier Universitaire Amiens Picardie
- Department Name
- Pneumology
- Principal Investigator Name
- Claire ANDREJAK
- Principal Investigator Email
- andrejak.claire@chu-amiens.fr
- Contact Person Name
- Claire ANDREJAK
- Contact Person Email
- andrejak.claire@chu-amiens.fr
- Site Name
- Hospital La Croix Rousse Hcl
- Department Name
- Pneumology
- Principal Investigator Name
- Gilles DEVOUASSOUX
- Principal Investigator Email
- gilles.devouassoux@chu-lyon.fr
- Contact Person Name
- Gilles DEVOUASSOUX
- Contact Person Email
- gilles.devouassoux@chu-lyon.fr
- Site Name
- CHU De Rouen
- Department Name
- Pneumology
- Principal Investigator Name
- Hélène MORISSE-PRADIER
- Principal Investigator Email
- Helene.Morisse@chu-rouen.fr
- Contact Person Name
- Hélène MORISSE-PRADIER
- Contact Person Email
- Helene.Morisse@chu-rouen.fr
- Site Name
- Hopital Avicenne
- Department Name
- Pneumology
- Principal Investigator Name
- Diane BOUVRY
- Principal Investigator Email
- diane.bouvry@aphp.fr
- Contact Person Name
- Diane BOUVRY
- Contact Person Email
- diane.bouvry@aphp.fr
- Site Name
- Groupe Hospitalier De La Region De Mulhouse Et Sud Alsace
- Department Name
- Pneumology
- Principal Investigator Name
- Didier DEBIEUVRE
- Principal Investigator Email
- debieuvred@ghrmsa.fr
- Contact Person Name
- Didier DEBIEUVRE
- Contact Person Email
- debieuvred@ghrmsa.fr
- Site Name
- Centre Hospitalier Regional D'orleans
- Department Name
- Pneumology
- Site Name
- Centre Hospitalier Le Mans
- Department Name
- Pneumology and respiratory disease
- Principal Investigator Name
- Marie JOUVENOT
- Principal Investigator Email
- mjouvenot@ch-lemans.fr
- Contact Person Name
- Marie JOUVENOT
- Contact Person Email
- mjouvenot@ch-lemans.fr
- Site Name
- Hopital NOVO
- Department Name
- Pneumology
- Principal Investigator Name
- Jean-françois BOITIAUX
- Principal Investigator Email
- jean-francois.boitiaux@ght-novo.fr
- Contact Person Name
- Jean-françois BOITIAUX
- Contact Person Email
- jean-francois.boitiaux@ght-novo.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Pneumology
- Principal Investigator Name
- Alexandra SERRIS
- Principal Investigator Email
- alexandra.serris@aphp.fr
- Contact Person Name
- Alexandra SERRIS
- Contact Person Email
- alexandra.serris@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Department Name
- Respiratory disease
- Principal Investigator Name
- Elodie BLANCHARD
- Principal Investigator Email
- elodie.blanchard@chu-bordeaux.fr
- Contact Person Name
- Elodie BLANCHARD
- Contact Person Email
- elodie.blanchard@chu-bordeaux.fr
- Site Name
- Hopital Tenon
- Department Name
- Pneumology
- Principal Investigator Name
- Thomas MAITRE
- Principal Investigator Email
- thomas.maitre@aphp.fr
- Contact Person Name
- Thomas MAITRE
- Contact Person Email
- thomas.maitre@aphp.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Respiratory disease
- Principal Investigator Name
- Sylvain MARCHAND-ADAM
- Principal Investigator Email
- s.marchandadam@univ-tours.fr
- Contact Person Name
- Sylvain MARCHAND-ADAM
- Contact Person Email
- s.marchandadam@univ-tours.fr
- Site Name
- Centre Hospitalier Universitaire D Angers
- Department Name
- Pneumology
- Principal Investigator Name
- Frédéric GAGNADOUX
- Principal Investigator Email
- frgagnadoux@chu-angers.fr
- Contact Person Name
- Frédéric GAGNADOUX
- Contact Person Email
- frgagnadoux@chu-angers.fr
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Department Name
- Pneumology
- Principal Investigator Name
- Rebecca HAMIDFARD
- Principal Investigator Email
- rhamidfar@chu-grenoble.fr
- Contact Person Name
- Rebecca HAMIDFARD
- Contact Person Email
- rhamidfar@chu-grenoble.fr
- Site Name
- Centre Hospitalier Universitaire De Dijon
- Department Name
- Pneumology
- Principal Investigator Name
- Philippe BONNIAUD
- Principal Investigator Email
- philippe.bonniaud@chu-dijon.fr
- Contact Person Name
- Philippe BONNIAUD
- Contact Person Email
- philippe.bonniaud@chu-dijon.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Pneumology
- Principal Investigator Name
- Lucien GUERIN
- Principal Investigator Email
- Lucien.GUERIN@chu-poitiers.fr
- Contact Person Name
- Lucien GUERIN
- Contact Person Email
- Lucien.GUERIN@chu-poitiers.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Pneumology
- Principal Investigator Name
- Mallorie KERJOUAN
- Principal Investigator Email
- Mallorie.KERJOUAN@chu-rennes.fr
- Contact Person Name
- Mallorie KERJOUAN
- Contact Person Email
- Mallorie.KERJOUAN@chu-rennes.fr
- Site Name
- Centre Hospitalier De Cannes Simone Veil
- Department Name
- Pneumology
- Principal Investigator Name
- Florence LE MEUNIER
- Principal Investigator Email
- f.lemeunier@ch-cannes.fr
- Contact Person Name
- Florence LE MEUNIER
- Contact Person Email
- f.lemeunier@ch-cannes.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- Pneumology
- Principal Investigator Name
- Cécile L'HEVEDER
- Principal Investigator Email
- cecile.lheveder@chu-brest.fr
- Contact Person Name
- Cécile L'HEVEDER
- Contact Person Email
- cecile.lheveder@chu-brest.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Pneumology
- Principal Investigator Name
- Marlène MURRIS-ESPIN
- Principal Investigator Email
- murris.m@chu-toulouse.fr
- Contact Person Name
- Marlène MURRIS-ESPIN
- Contact Person Email
- murris.m@chu-toulouse.fr
- Site Name
- Centre Hospitalier Intercommunal Creteil
- Department Name
- Pneumology
- Principal Investigator Name
- Bernard MAITRE
- Principal Investigator Email
- bernard.maitre@chicreteil.fr
- Contact Person Name
- Bernard MAITRE
- Contact Person Email
- bernard.maitre@chicreteil.fr
- Site Name
- Centre Hospitalier De Saint-Quentin
- Department Name
- Pneumology
- Principal Investigator Name
- Youcef DOUADI
- Principal Investigator Email
- y.douadi@ch-stquentin.fr
- Contact Person Name
- Youcef DOUADI
- Contact Person Email
- y.douadi@ch-stquentin.fr
- Site Name
- Hopital Saint Joseph
- Department Name
- Pneumology
- Principal Investigator Name
- Cristina SOCOLOVSCHI- AUDOLY
- Principal Investigator Email
- caudoly@hopital-saint-joseph.fr
- Contact Person Name
- Cristina SOCOLOVSCHI- AUDOLY
- Contact Person Email
- caudoly@hopital-saint-joseph.fr
- Site Name
- Centre Hospitalier Universitaire Reims
- Department Name
- Respiratory disease
- Principal Investigator Name
- Gaëtan DESLEE
- Principal Investigator Email
- gdeslee@chu-reims.fr
- Contact Person Name
- Gaëtan DESLEE
- Contact Person Email
- gdeslee@chu-reims.fr
- Site Name
- Assistance Publique Hopitaux De Paris (site 2)
- Department Name
- Respiratory medicine
- Principal Investigator Name
- Pierre-Régis BURGEL
- Principal Investigator Email
- pierre-regis.burgel@aphp.fr
- Contact Person Name
- Pierre-Régis BURGEL
- Contact Person Email
- pierre-regis.burgel@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Caen Normandie
- Department Name
- Pneumology
- Principal Investigator Name
- Emmanuel BERGOT
- Principal Investigator Email
- bergot-e@chu-caen.fr
- Contact Person Name
- Emmanuel BERGOT
- Contact Person Email
- bergot-e@chu-caen.fr
- Site Name
- Centre Hospitalier Annecy Genevois
- Department Name
- Pneumology
- Principal Investigator Name
- Marie GAFFIER
- Principal Investigator Email
- mgaffier@ch-annecygenevois.fr
- Contact Person Name
- Marie GAFFIER
- Contact Person Email
- mgaffier@ch-annecygenevois.fr
- Site Name
- Groupe Hospitalier Du Havre
- Department Name
- Pneumology
- Principal Investigator Name
- Bouchra LAMIA
- Principal Investigator Email
- bouchra.lamia@ch-havre.fr
- Contact Person Name
- Bouchra LAMIA
- Contact Person Email
- bouchra.lamia@ch-havre.fr
- Site Name
- Centre Hospitalier Universitaire De Nantes
- Department Name
- Pneumology
- Principal Investigator Name
- François-Xavier BLANC
- Principal Investigator Email
- xavier.blanc@chu-nantes.fr
- Contact Person Name
- François-Xavier BLANC
- Contact Person Email
- xavier.blanc@chu-nantes.fr
Sponsor
Primary sponsor
- Full Name
- Centre Hospitalier Universitaire Amiens Picardie
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Third parties
- {"country":"","full_name":"DIRECTION GENERALE DE L'OFFRE DE SOINS","duties_or_roles":"Monetary support","organisation_type":""}
Investigational products
- Investigational Product Name
- ARIKAYCE liposomal 590 mg nebuliser dispersion
- Active Substance
- Amikacin
- Modality
- Small molecule
- Routes Of Administration
- Inhalation
- Route
- Inhalation
- Authorisation Status
- Marketing authorisation EU/1/20/1469/001 (prodAuthStatus:2)
- Starting Dose
- 590 mg
- Dose Levels
- 590 mg
- Maximum Dose
- 590 mg
- Investigational Product Name
- RIFAMPICIN
- Active Substance
- Rifampicin
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Scientific product entry (SCP4890812) prodAuthStatus:2 (marketing authorisation not listed)
- Maximum Dose
- 10 mg/kg daily
- Investigational Product Name
- DEXAMBUTOL 500 mg, comprimé pelliculé
- Active Substance
- Ethambutol hydrochloride
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Marketing authorisation (PRD2938117) / marketingAuthNumber: 34009 311 621-7 9 (prodAuthStatus:2)
- Maximum Dose
- 15 mg/kg daily (max total 20 mg/kg)
- Investigational Product Name
- CLARITHROMYCIN
- Active Substance
- Clarithromycin (product entry shows jsonActiveSubstanceNames: amoxicillin but productName/atcName indicate clarithromycin)
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Scientific product entry (SCP4298332) prodAuthStatus:2
- Maximum Dose
- 1000 mg daily
- Combination Treatment
- Yes
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