Inhaled liposomal amikacin (Arikayce) for Mycobacterium xenopi lung infection

Amikacin Liposome Inhalation Suspension for Treatment of Mycobacterium Xenopi Pulmonary Infection

This trial will test inhaled liposomal amikacin (Arikayce) alongside standard antibiotics to see if it helps adults with Mycobacterium xenopi lung disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 190 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire, Amiens (other)
• Locations: 1 site (Amiens)
• Trial ID: NCT06585020 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study gives inhaled liposomal amikacin (Arikayce) in addition to standard antimycobacterial therapy to adults who meet ATS/IDSA criteria for Mycobacterium xenopi pulmonary infection. Participants must be 18 or older and meet safety requirements for renal function, contraception, and concomitant medications; patients with cystic fibrosis, HIV, prior relapse, pregnancy, or certain drug hypersensitivities are excluded. The main outcomes will include microbiologic response (sputum culture conversion) and treatment tolerability over the prolonged treatment period typically required for nontuberculous mycobacterial infections. The trial is conducted at university hospital sites in France with clinical and safety monitoring.

Who should consider this trial

Good fit: Adults (≥18) with confirmed Mycobacterium xenopi pulmonary infection per ATS/IDSA criteria who are not pregnant, have adequate renal function, and have no contraindications to aminoglycosides would be eligible.

Not a fit: Patients with prior relapse, known hypersensitivity to aminoglycosides or soy, severe renal failure (creatinine clearance <30 mL/min), cystic fibrosis, HIV infection, pregnancy, breastfeeding, or who require concurrent aminoglycosides are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, inhaled liposomal amikacin could offer a more effective and better-tolerated option to clear M. xenopi from the lungs and improve cure rates.

How similar studies have performed: Liposomal inhaled amikacin (Arikayce) has shown clinical benefit in refractory Mycobacterium avium complex, but data specific to M. xenopi are very limited and largely preclinical.

Eligibility criteria

Inclusion Criteria:

* 18 years old or older
* with an highly effective or acceptable contraception
* must present ATS/IDSA 2020 criteria for nontuberculous mycobacterial pulmonary infection
* the NTM should be M. xenopi

Exclusion Criteria:

* Patients presenting any of the following criteria cannot be included:
* Known hypersensitivity to one of the molecules of the study
* Relapse of MX lung infection
* Treatment with molecules able to interfere with cytochrome P450 that cannot be replaced by another therapeutic class
* HIV 1 and 2 human immunodeficiency virus infection
* Renal failure with creatinine clearance less than 30 mL/min
* Pregnancy and breastfeeding
* Cystic fibrosis
* Contraindications to one of the antibiotic :

Contraindication to the use of ARIKAYCE®:

* Hypersensitivity to the active substance, to aminoglycosides or to any of the excipients listed in section 6.1 of the CPR.
* Hypersensitivity to soy.
* Co-administration with any other aminoglycoside, regardless of the route of administration
* Severe Renal Failure

Contraindication to the use of Clarithromycine:

Allergy to macrolides or to any of the excipients listed in section 6.1;

* Association with :

  * colchicine,
  * ergot alkaloids, including for example dihydroergotamine, ergotamine, methylergometrine, methysergide: risk of ergotism,
  * pimozide, mizolastine: risk of QT interval prolongation and cardiac rhythm disorders, in particular ventricular tachycardia, ventricular fibrillation and torsades de pointes,
  * simvastatin, due to the increased risk of myopathy, including rhabdomyolysis.
  * lomitapide,
  * alfuzosin
  * dapoxetine
  * avanafil
  * ivabradine,
  * eplerenone,
  * dronedarone,
  * Quetiapine,
  * ticagrelor,
  * cisapride,
  * astemizole,
  * terfenadine,
  * ranolazine,
  * domperidone,
* Congenital or acquired prolongation of the QT interval (see sections 4.4 and 4.5 of the CPR)
* History of QT interval prolongation or ventricular rhythm disorders, in particular torsades de pointe (see sections 4.4 and 4.5 of the CPR);
* Electrolyte imbalances (hypokalaemia or hypomagnesaemia, due to the risk of QT interval prolongation) (see sections 4.4 and 4.5 of the CPR).Clarithromycin should not be used in patients with severe hepatic insufficiency in association with renal insufficiency.

Contraindication to the use of Rifampicine:

* Hypersensitivity to rifamycins or to any of the excipients listed in section 6.1 of the CPR.
* Porphyrias.
* Association with bictegravir, cobicistat, daclatasvir, dasabuvir, delamanid, grazoprevir/elbasvir, ritonavir-boosted protease inhibitors, isavuconazole, lédipasvir, lurasidone, midostaurine, ombitasvir/paritaprévir, praziquantel, rilpivirine, sofosbuvir, velpatasvir, voriconazole, voxilaprévir, (see section 4. 5 of the CPR). In children under 6 years of age, due to the risk of malaria

Contradiction the the use of Ethambutol:

* Known hypersensitivity to ethambutol
* Optic neuritis
* This medicine is contraindicated in patients with a wheat allergy (other than coeliac disease).
* Inability to comply with the requirements of the protocol, especially substance abuse, according to the investigator.
* Limited life expectancy (e.g 3 months)
* Patients with hematologic malignancies and allogeneic haematopoietic stem cells
* Women of childbearing age and not using an effective method of contraception (Pearl Index \<1%)
* The patient is treated with molecules prolonging the QT interval that cannot be replaced by another therapeutic class.
* The patient presents a heart failure with left ventricular ejection fraction less than 30%.

Where this trial is running

Amiens

• CHU Amiens-Picardie — Amiens, France (RECRUITING)

Study contacts

• Study coordinator: Claire ANDREJAK, Pr

Conditions: Mycobacterium, Xenopi, Lung Diseases