Pneumocystis PneumoniaPhase 1/2CaspoNEBNCT06892951
CaspoNEB: Efficacy and Safety of Caspofungin Aerosols for the Curative Treatment of Pneumocystis Pneumonia
A Phase 1/2 study testing Caspofungin Acetate 50 MG and Physiologic saline in people with Pneumocystis Pneumonia and Pneumocystis Jirovecii Infection, run by University Hospital, Tours at 3 sites in France.
Trial summary
To assess the efficacy of administrating daily caspofungin aerosols versus placebo for seven days, in adjunction of conventional systemic antifungal therapy during curative treatment of Pneumocystis pneumonia, on the clinical outcome at the end of the nebulized therapy, in order to support a "GO / NO GO" decision… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pneumocystis Pneumonia, Pneumocystis Jirovecii Infection, Pneumocystis Infections
- What is being tested?
- Caspofungin Acetate 50 MG and Physiologic saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 3 sitesFrance
- Study dates
- 2 Dec 2025to Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female ≥18 years
- Medical management of Pneumocystis pneumonia based on :
- Microbiological diagnosis of Pneumocystis pneumonia
- Respiratory support (oxygen therapy or ventilatory assistance)
- Systemic co-trimoxazole therapy or systemic second-line anti-Pneumocystis salvage therapy (switch to another anti-Pneumocystis drug is possible, but should be notified) (initiated within 48 hours or less before enrolment)
- Person affiliated to a French social security system or equivalent
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- Written informed consent obtained from the participant or, if the patient is not able to give consent from representative (trusted person, family member) or if the delay in obtaining the consent is assumed not compatible with the enrollment requirements, a temporary approval can be obtained from the investigator. In all cases, the patient's written informed consent will have to be obtained as soon as possible.
- Non-inclusion criteria:
- Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship). Pregnancy test to be performed in all women from 15 to 45 years old who have not had an ovariectomy.
- Other indication(s) for systemic administration of an echinocandin drug
- Known allergy to echinocandin drugs
- Absolute contraindication to aerosol therapy
- Concomitant co-infection at time of diagnosis (except HIV infection)
- Severe liver impairment (i.e. documented severe liver cirrhosis (Child C), or Factor-V protein < 50% and/or INR for prothrombin time of blood coagulation > 1.5)
- history of toxic epidermal necrosis (TEN) and Steven-Johnson syndrome (SJS)
- Participation in other pharmacological study that focuses on echinocandins and/or anti-infectious aerosol therapy or other anti-pneumocystis treatment
- Participation in a trial with an investigational product known to have pulmonary toxicity or of which the safety is not known
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites, 3 recruiting
- Recruiting
CHU Orléans
Orléans
François BARBIER
- Not yet recruiting
CHU Tours
Tours, 37000
Elodie MOUSSET, MSc, +33 2 47 47 46 65, E.MOUSSET@chu-tours.fr
Guillaume DESOUBEAUX, MD PhD, +33 2 34 37 89 26, guillaume.desoubeaux@univ-tours.fr
- Recruiting
CHRU Tours
Tours
Stephan EHRMANN
About this study
Official title: Phase I/II Safety lead-in Randomized Blind Placebo-controlled Clinical Trial: Efficacy and Safety of Caspofungin Aerosols for the Curative Treatment of Pneumocystis Pneumonia in Adjunction of Conventional Systemic Antifungal Therapy
To assess the efficacy of administrating daily caspofungin aerosols versus placebo for seven days, in adjunction of conventional systemic antifungal therapy during curative treatment of Pneumocystis pneumonia, on the clinical outcome at the end of the nebulized therapy, in order to support a "GO / NO GO" decision towards a phase III trial of nebulized caspofungin in those patients.
Read the detailed description
Pneumocystis jirovecii is an airborne-transmissible fungus which can induce pneumonia with severely impaired lung function, especially in immunocompromised patients. At least 1,000 new cases of Pneumocystis pneumonia occur each year in France with approximately 50% of cases suffering from hypoxemia. Around 15% HIV+ and 50% HIV- subjects require mechanical ventilation, and mean duration of hospitalization is about 30 days. Average mortality rate is ≈20% at 3 months, higher for critically ill patients (30%-60%).
To date, cotrimoxazole represents the gold standard anti-Pneumocystis treatment commonly associated with systemic corticosteroids in case of moderate-to-severe infection. However, treatment is long (several weeks) to achieve clearance of the fungus, which might favor lung sequelae like persistent inflammation or post-infectious fibrosis. Furthermore, therapeutic failures have been reported as high as 9-44% of patients. Five other drugs have been commonly used as curative alternatives to cotrimoxazole against P. jirovecii: pentamidine, primaquine + clindamycin, dapsone and atovaquone. Some are responsible for serious side effects, while others are complex to administer or less efficient. All exhibit clinically important drug-drug interactions. Therefore, in such a context, it is important to test new drugs and/or alternative delivery routes for existing therapies.
Echinocandin drugs, including caspofungin, are usually administered daily to treat invasive candidiasis and aspergillosis. They target the fungal cell wall, thus inhibiting the β-(1,3)-D glucan synthase enzyme. Intravenous (IV) echinocandins are generally well tolerated and are not responsibles for major drug-drug interactions. IV caspofungin was also proven effective in animal models of Pneumocystis infection and significantly improve the overall survival. Two human studies showed that in-hospital and 3-month mortality rates were similar between patients receiving daily IV echinocandin and those receiving co-trimoxazole alone. Several case reports also showed 47 successful outcomes with IV caspofungin, alone or in combination with standard treatment. A recent study reported better response and lower in-hospital mortality in patients receiving the combination of cotrimoxazole + IV caspofungin with no severe adverse events. Therefore, IV echinocandins are now recommended in the European therapeutic guidelines for non-HIV patients as a salvage therapy (CII-grade) in association with co-trimoxazole.
However, high molecular weight and elevated protein binding hamper optimal diffusion of IV caspofungin towards the lung alveoli (<5% plasma concentration), where P. jirovecii thrives. Administration through an aerosol directly delivered into the lung may circumvent this limitation. Technical feasibility of echinocandin nebulization was demonstrated in vitro with several commercial nebulizers that provided aerosol particles with adequat size and pH to ensure lung tolerance. In vivo, nebulized caspofungin, at a dosage equivalent to the usual IV dosage, showed an excellent safety profile in rats. It also reduced the fungal burden by -99% and induced elevated and prolonged concentrations of the drug in the lungs (almost 50% of the total amounts of caspofungin initially deposited into the lungs of infected rats were still detectable at 48 hours) - largely above the usual minimal inhibitory concentrations of fungal pathogens -, while caspofungin detection was almost null in other organs and blood.
Therefore, we hypothesize herein the therapeutic interest of caspofungin aerosols in adjunction with conventional antifungal therapy, as first-line curative treatment, to enhance the clinical recovery and to reduce the morbidity due to Pneumocystis pneumonia. As no clinical trials have been worldwide initiated, human efficacy and safety data of nebulized caspofungin are still lacking and will be first investigated in this study in patients. Thus organized in two successive parts, this phase I/II clinical trial represents a mandatory prelude for this original administration modality of caspofungin.
- Being tested
- Caspofungin Acetate 50 MG, Physiologic saline
- Keywords
- ventilation, Pneumocystis, caspofungin, echinocandin, aerosol, inhalation, nebulization, interstitial pneumonia
- Medical subject headings
- Pneumonia, Pneumocystis, Pneumocystis Infections, Respiratory Aspiration, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caspofungin Acetate 50 MGDrug
The experimental treatment will be administered once daily for up to seven days, through the nebulization route by the means of a disposable vibrating mesh Aeroneb solo® nebulizer with the valved mask (Galway, Ireland). Before generating aerosol, resuspension of the caspofungin powder will be carried out in the same manner than for the IV route, into 10.5 mL saline serum. Preparation of the experimental drug (re-suspension) will be unblindly carried out in a distinct medical office by a nurse neither involved in the healthcare of the included patients, nor in the other parts of the study, data recording or outcome assessment. Once reconstituted, the suspension is expected to be limpid, with neither odour nor foam. Thereafter, its administration will be blindly completed by the clinical staff in charge of the enrolled patient.
Physiologic salineDrug
Procedures will be exactly the same than those described above for the experimental group, but caspofungin will be replaced during the seven days of intervention by 10mL of 0.9% saline nebulized in the control group for a 15 minute-long process of nebulization (from d-1 to d-7).
| Study group | Role | What they receive |
|---|---|---|
| Part 2 - randomized study (group 1) | Experimental | Conventional systemic antifungal treatment (systemic co-trimoxazole or systemic second line anti-Pneumocystis salvage therapy) + aerosols of echinocandin (50 mg caspofungin) during one to seven days (according to the regimen retained from the results of part 1 from day-1 to d-7) using vibrating mesh nebulization device Receives: Drug: Caspofungin Acetate 50 MG |
| Part 2 - randomized study (group 2) | Placebo comparator | Control group: (in part 2 only) Conventional systemic antifungal treatment (systemic co-trimoxazole or systemic second-line anti-Pneumocystis salvage therapy) + aerosols of placebo (0.9% saline in a volume equivalent to the experimental group) during one to seven days (according to the regimen retained from part 1 results) using vibrating mesh nebulization device Receives: Drug: Physiologic saline |
| Part 1 - open study | Experimental | open-label non-randomized group, with ascending scheme regarding the dose and rhythm of administration over one week, depending on the tolerance, and closely monitored in ICU to ensure that caspofungin is well tolerated via the inhaled route, and to provide data supporting the proposed administration scheme for part 2.
* the first two patients (included one by one) will receive two aerosols (5 mg) during the first week, four days apart on d-1 and d-5 (level 1);
* the third and fourth will receive two aerosols (15 mg) during the first week, four days apart on d-1 and d-5 (level 2);
* the fifth and sixth will receive two aerosols (50 mg) during the first week, four days apart on d-1 and d-5 (level 3);
* the seventh and eighth patients will receive four aerosols (50 mg) two days apart during one week, at d-1, then d-3, d-5 and d-7 (level 4);
* the last two patients will have daily aerosols during the first week, from d-1 to d-7 (level 5) Receives: Drug: Caspofungin Acetate 50 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: safety of inhaled caspofungin
- frequency of adverse events
- severity of adverse events
Measured: D-7 (day-7)
Part 2: proportion of patients alive and with a favorable clinical course* at the seventh day (day-7) after the first administration.
Composite outcome defined by at least one of the two following items persisting ≥24 hours in alive patients:
- Relative reduction (de-escalation or withdrawal) of respiratory assistance due to clinical improvement (depending on the initial support):
- extubation, or
- weaning of non-invasive ventilatory support, or
- weaning of nasal high-flow or low-flow oxygen therapy; (NB: all participating centers will implement uniform protocols for ventilatory assistance weaning)
- Occurrence of a +50% increase in oxygenation (PaO2 / FiO2 ratio vs. the worst value observed after inclusion).
Measured: D7 (day-7)
Secondary outcomes (6)
Individual components of the composite primary outcome at day-7 (d-7)
- All-cause mortality and Pneumocystis pneumonia-related mortality
- Improvement of respiratory function:
- Proportion of patients alive and with relative reduction (de-escalation or withdrawal) of respiratory assistance (in percentage)
- Proportion of patients alive and with a +50% increase in oxygenation (PaO2 / FiO2 ratio vs. the worst value observed after inclusion) (in percentage)
Measured: D7 (day-7)
Safety of nebulized caspofungin in patients with Pneumocystis pneumonia through
- Occurrence of serious and non-serious pulmonary adverse events and adverse effects at day-1 (d-1), d-2, d-3, d-4, d-5, d-6, and d-7 (with active monitoring of the nebulization procedure), and serious pulmonary adverse events and adverse effects at hospital discharge, d-28 and d-90
- Occurrence of other serious adverse events and adverse effects at day-1 (d-1), d-2, d-3, d-4, d-5, d-6, d-7, hospital discharge, d-28 and d-90
- Liver and kidney markers at day 1 (d-1), d-3, d-7, d-28 and d-90
- transaminases (in international units/liter)
- glutamate transferase (in international units/liter)
- alkaline phosphatase (in international units/liter)
- serum creatinine (in micromol/liter)
- urea (in millimol/liter)
- Blood counts (same dates)
- complete blood count (in giga/liter)
- platelets (in giga/liter)
- Serum electrolytes (same dates)
- sodium (in mmol/liter)
- potassium (in mmol/liter)
- chloride (in mmol/liter)
- bicarbonates (in mmol/liter)
Measured: day-1 (d-1), d-2, d-3, d-4, d-5, d-6, and d-7
Pharmacokinetics of nebulized caspofungin
in blood at 0, 2, 4, 6, 12, 24 hours, plus residual concentration at day-3 (d-3) and d-7 for the five first included patients receiving caspofungin, and in tracheo-bronchial aspirates at 4, 6, 24 h, at day-3 (d-3) and d-7 (or just before extubation if still alive at time of extubation) for the five first included patients receiving caspofungin and who are intubated. Caspofungin concentration measurements (in milligram/liter) will be centrally carried out at Tours university hospital at the end of the study only for patients who received nebulized caspofungin (intervention group), once the blind process will be lifted).
Measured: 0, 2, 4, 6, 12, 24 hours, plus residual concentration at day (d-3) and d-7
Mortality
- All-cause at hospital discharge, day-28 (d-28) and d-90
- Pneumocystis pneumonia-related at hospital discharge, day-28 (d-28) and d-90
Measured: day-28 (d-28) and d-90
Morbidity
- Number of days alive without any ventilatory / oxygen support
- Duration to clinical stability (from inclusion to hospital discharge:
- maximum daily temperature ≤ 37.8 °C
- maximum daily heart pace ≤ 100 bpm
- maximum daily respiratory pace ≤ 24 cpm
- minimum daily systolic blood pressure ≥ 90 mmHg
- arterial oxygenation saturation ≥ 90% or PaO2 ≥ 60 mmHg while breathing room air, or PaO2/FiO2 ratio ≥ 285 mmHg, without an increase in the intensity of the ventilatory support
- normal mental status
- Duration of invasive ventilatory support
- Duration of invasive and non-invasive ventilatory support
- Duration to clinical healing :
- clinical stability (cf. above)
- 24h weaning of mechanical respiratory support due to patient's clinical improvement
- Duration of hospital stay (in days)
- Duration of ICU stay (in days)
- Change in the sepsis-related organ failure assessments (SOFA) score
- Requirement of a second-line (salvage) anti-Pneumocystis curative therapy (yes or no)
Measured: day-1 (d-1), d-7 and d-21
Pulmonary and systemic markers of lung infection (to assess the fungal clearance)
- Evolution of hypoxemia:
- alveolar-to-arterial oxygen gradient, ratio of arterial partial pressure in oxygen and pulsed oxymetry to fraction of inspired oxygen (in millimeter Hg)
- LDH enzyme in blood (in international units/liter)
- BDG fungal antigen in blood (in pigogram / milliliter)
- RT-qPCR for P jirovecii nucleic acids in blood and in tracheal aspirates (in number of amplification cycles)
- Impact on the micro-organism diversity in respiratory airways and infections
- monitoring the expression of specific genes for distinguishing the relative representativeness between P. jirovecii asci and trophic forms from trachea-bronchial aspirates
- identification and counting of fungal colonies from trachea-bronchial aspirates (in number of colony-forming units (CFU))
- identification and counting of bacterial colonies from trachea-bronchial aspirates (in CFU)
- Genotyping of P. jirovecii strains based on microsatellites markers and sequencing of DHPS/DHFR genes in respiratory fluids
Measured: day-1 (d-1), d-3, d-7, d-28 and d-90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study start2 Dec 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Pneumocystis PneumoniaStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The protocol will be carried out in a sequential manner to first provide safety data and the optimal dosing regimen on inhaled caspofungin, prior to inclusion of all the other patients: 1. Part 1: open-label, one arm, non-randomized, three centres study including six patients with ascending scheme regarding the rhythm of administration over one week, depending on the tolerance and closely monitored in intensive care unit to ensure that caspofungin is well tolerated via the inhaled route and to provide data supporting the proposed dose for part 2 (PK modeling) 2. Part 2: comparative, two arms, add-on, multicenter, individually-randomized placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Angers, Centre Hospitalier Universitaire de Besancon, University Hospital, Bordeaux, University Hospital, Brest, Centre Hospitalier Universitaire Dijon, University Hospital, Grenoble, University Hospital, Lille, University Hospital, Limoges, Hospices Civils de Lyon, University Hospital, Montpellier, Nantes University Hospital, Centre Hospitalier Universitaire de Nice, Hospital Avicenne, Henri Mondor University Hospital, Hopital Foch, Hôpital Necker-Enfants Malades, Pitié-Salpêtrière Hospital, Poitiers University Hospital, Reims University hospital, Ohre Pharma, Aerogen, Wako Diagnostics, Cape Cod Incorporated, Institut National de la Santé Et de la Recherche Médicale, France, Tours university, Amiens University Hospital, Rennes University Hospital
- Responsible party
- Sponsor
- Investigators
- Guillaume DESOUBEAUX, Prof, Study director, University Hospital of TOURSStephan EHRMANN, Prof, Study director, University Hospital of TOURSAdrien LEMAIGNEN, Dr, Study director, University Hospital of TOURS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06892951
- Sponsor's protocol ID
- 2022-DR329-CaspoNEB
- Other IDs
- 2023-508861-34-00, 2023
- Acronym
- CaspoNEB
- Status last verified
- Oct 2026
- First submitted
- 18 Jan 2024
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All research data can be requested
Publications
Limper AH. Alveolar macrophage and glycoprotein responses to Pneumocystis carinii. Semin Respir Infect. 1998 Dec;13(4):339-47.
PubMed 9872631McKinnell JA, Cannella AP, Kunz DF, Hook EW 3rd, Moser SA, Miller LG, Baddley JW, Pappas PG. Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected persons. Transpl Infect Dis. 2012 Oct;14(5):510-8. doi: 10.1111/j.1399-3062.2012.00739.x. Epub 2012 May 1.
PubMed 22548840Lobo ML, Esteves F, de Sousa B, Cardoso F, Cushion MT, Antunes F, Matos O. Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for pneumocystis pneumonia: a pilot study in mice. PLoS One. 2013 Aug 5;8(8):e70619. doi: 10.1371/journal.pone.0070619. Print 2013.
PubMed 23940606Wong-Beringer A, Lambros MP, Beringer PM, Johnson DL. Suitability of caspofungin for aerosol delivery: physicochemical profiling and nebulizer choice. Chest. 2005 Nov;128(5):3711-6. doi: 10.1378/chest.128.5.3711.
PubMed 16304338Ehrmann S, Mercier E, Vecellio L, Ternant D, Paintaud G, Dequin PF. Pharmacokinetics of high-dose nebulized amikacin in mechanically ventilated healthy subjects. Intensive Care Med. 2008 Apr;34(4):755-62. doi: 10.1007/s00134-007-0935-1. Epub 2007 Nov 29.
PubMed 18046534Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019.0555.
PubMed 30776290Desoubeaux G, Lemaignen A, Ehrmann S. Scientific rationale for inhaled caspofungin to treat Pneumocystis pneumonia: A therapeutic innovation likely relevant to investigate in a near future.... Int J Infect Dis. 2020 Jun;95:464-467. doi: 10.1016/j.ijid.2020.03.029. Epub 2020 Mar 16. No abstract available.
PubMed 32194238Le Gal S, Toubas D, Totet A, Dalle F, Abou Bacar A, Le Meur Y, Nevez G; Anofel Association. Pneumocystis Infection Outbreaks in Organ Transplantation Units in France: A Nation-Wide Survey. Clin Infect Dis. 2020 May 6;70(10):2216-2220. doi: 10.1093/cid/ciz901.
PubMed 31633150Desoubeaux G, Dominique M, Morio F, Thepault RA, Franck-Martel C, Tellier AC, Ferrandiere M, Hennequin C, Bernard L, Salame E, Bailly E, Chandenier J. Epidemiological Outbreaks of Pneumocystis jirovecii Pneumonia Are Not Limited to Kidney Transplant Recipients: Genotyping Confirms Common Source of Transmission in a Liver Transplantation Unit. J Clin Microbiol. 2016 May;54(5):1314-20. doi: 10.1128/JCM.00133-16. Epub 2016 Mar 2.
PubMed 26935726Alanio A, Desoubeaux G, Sarfati C, Hamane S, Bergeron A, Azoulay E, Molina JM, Derouin F, Menotti J. Real-time PCR assay-based strategy for differentiation between active Pneumocystis jirovecii pneumonia and colonization in immunocompromised patients. Clin Microbiol Infect. 2011 Oct;17(10):1531-7. doi: 10.1111/j.1469-0691.2010.03400.x. Epub 2011 Apr 12.
PubMed 20946413Nevez G, Le Gal S. Caspofungin and Pneumocystis Pneumonia: It Is Time To Go Ahead. Antimicrob Agents Chemother. 2019 Sep 23;63(10):e01296-19. doi: 10.1128/AAC.01296-19. Print 2019 Oct. No abstract available.
PubMed 31548210Peghin M, Fishman JA, Grossi PA. Pneumocystis jiroveci : still troublesome to diagnose and treat. Curr Opin Infect Dis. 2025 Dec 1;38(6):522-529. doi: 10.1097/QCO.0000000000001155. Epub 2025 Oct 17.
PubMed 41151592
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Safety lead-in Randomized Blind Placebo-controlled Clinical Trial: Efficacy and Safety of Caspofungin Aerosols for the Curative Treatment of Pneumocystis Pneumonia in Adjunction of Conventional Systemic Antifungal Therapy
- ClinicalTrials.gov ID
- NCT06892951
- Acronym / sponsor ID
- CaspoNEB / 2022-DR329-CaspoNEB
- Keywords
- ventilation, Pneumocystis, caspofungin, echinocandin, aerosol, inhalation, nebulization, interstitial pneumonia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Collaborators
- University Hospital, Angers, Centre Hospitalier Universitaire de Besancon, University Hospital, Bordeaux, University Hospital, Brest, Centre Hospitalier Universitaire Dijon, University Hospital, Grenoble, University Hospital, Lille, University Hospital, Limoges, Hospices Civils de Lyon, University Hospital, Montpellier, Nantes University Hospital, Centre Hospitalier Universitaire de Nice, Hospital Avicenne, Henri Mondor University Hospital, Hopital Foch, Hôpital Necker-Enfants Malades, Pitié-Salpêtrière Hospital, Poitiers University Hospital, Reims University hospital, Ohre Pharma, Aerogen, Wako Diagnostics, Cape Cod Incorporated, Institut National de la Santé Et de la Recherche Médicale, France, Tours university, Amiens University Hospital, Rennes University Hospital
- Study start
- 2 Dec 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 25 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the efficacy of administrating daily caspofungin aerosols versus placebo for seven days, in adjunction of conventional systemic antifungal therapy during curative treatment of Pneumocystis pneumonia, on the clinical outcome at the end of the nebulized therapy, in order to support a "GO / NO GO" decision towards a phase III trial of nebulized caspofungin in those patients.
Detailed description
Pneumocystis jirovecii is an airborne-transmissible fungus which can induce pneumonia with severely impaired lung function, especially in immunocompromised patients. At least 1,000 new cases of Pneumocystis pneumonia occur each year in France with approximately 50% of cases suffering from hypoxemia. Around 15% HIV+ and 50% HIV- subjects require mechanical ventilation, and mean duration of hospitalization is about 30 days. Average mortality rate is ≈20% at 3 months, higher for critically ill patients (30%-60%).
To date, cotrimoxazole represents the gold standard anti-Pneumocystis treatment commonly associated with systemic corticosteroids in case of moderate-to-severe infection. However, treatment is long (several weeks) to achieve clearance of the fungus, which might favor lung sequelae like persistent inflammation or post-infectious fibrosis. Furthermore, therapeutic failures have been reported as high as 9-44% of patients. Five other drugs have been commonly used as curative alternatives to cotrimoxazole against P. jirovecii: pentamidine, primaquine + clindamycin, dapsone and atovaquone. Some are responsible for serious side effects, while others are complex to administer or less efficient. All exhibit clinically important drug-drug interactions. Therefore, in such a context, it is important to test new drugs and/or alternative delivery routes for existing therapies.
Echinocandin drugs, including caspofungin, are usually administered daily to treat invasive candidiasis and aspergillosis. They target the fungal cell wall, thus inhibiting the β-(1,3)-D glucan synthase enzyme. Intravenous (IV) echinocandins are generally well tolerated and are not responsibles for major drug-drug interactions. IV caspofungin was also proven effective in animal models of Pneumocystis infection and significantly improve the overall survival. Two human studies showed that in-hospital and 3-month mortality rates were similar between patients receiving daily IV echinocandin and those receiving co-trimoxazole alone. Several case reports also showed 47 successful outcomes with IV caspofungin, alone or in combination with standard treatment. A recent study reported better response and lower in-hospital mortality in patients receiving the combination of cotrimoxazole + IV caspofungin with no severe adverse events. Therefore, IV echinocandins are now recommended in the European therapeutic guidelines for non-HIV patients as a salvage therapy (CII-grade) in association with co-trimoxazole.
However, high molecular weight and elevated protein binding hamper optimal diffusion of IV caspofungin towards the lung alveoli (<5% plasma concentration), where P. jirovecii thrives. Administration through an aerosol directly delivered into the lung may circumvent this limitation. Technical feasibility of echinocandin nebulization was demonstrated in vitro with several commercial nebulizers that provided aerosol particles with adequat size and pH to ensure lung tolerance. In vivo, nebulized caspofungin, at a dosage equivalent to the usual IV dosage, showed an excellent safety profile in rats. It also reduced the fungal burden by -99% and induced elevated and prolonged concentrations of the drug in the lungs (almost 50% of the total amounts of caspofungin initially deposited into the lungs of infected rats were still detectable at 48 hours) - largely above the usual minimal inhibitory concentrations of fungal pathogens -, while caspofungin detection was almost null in other organs and blood.
Therefore, we hypothesize herein the therapeutic interest of caspofungin aerosols in adjunction with conventional antifungal therapy, as first-line curative treatment, to enhance the clinical recovery and to reduce the morbidity due to Pneumocystis pneumonia. As no clinical trials have been worldwide initiated, human efficacy and safety data of nebulized caspofungin are still lacking and will be first investigated in this study in patients. Thus organized in two successive parts, this phase I/II clinical trial represents a mandatory prelude for this original administration modality of caspofungin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- The protocol will be carried out in a sequential manner to first provide safety data and the optimal dosing regimen on inhaled caspofungin, prior to inclusion of all the other patients: 1. Part 1: open-label, one arm, non-randomized, three centres study including six patients with ascending scheme regarding the rhythm of administration over one week, depending on the tolerance and closely monitored in intensive care unit to ensure that caspofungin is well tolerated via the inhaled route and to provide data supporting the proposed dose for part 2 (PK modeling) 2. Part 2: comparative, two arms, add-on, multicenter, individually-randomized placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Part 2 - randomized study (group 1) | Experimental | Drug: Caspofungin Acetate 50 MGConventional systemic antifungal treatment (systemic co-trimoxazole or systemic second line anti-Pneumocystis salvage therapy) + aerosols of echinocandin (50 mg caspofungin) during one to seven days (according to the regimen retained from the results of part 1 from day-1 to d-7) using vibrating mesh nebulization device |
| Part 2 - randomized study (group 2) | Placebo comparator | Drug: Physiologic salineControl group: (in part 2 only) Conventional systemic antifungal treatment (systemic co-trimoxazole or systemic second-line anti-Pneumocystis salvage therapy) + aerosols of placebo (0.9% saline in a volume equivalent to the experimental group) during one to seven days (according to the regimen retained from part 1 results) using vibrating mesh nebulization device |
| Part 1 - open study | Experimental | Drug: Caspofungin Acetate 50 MGopen-label non-randomized group, with ascending scheme regarding the dose and rhythm of administration over one week, depending on the tolerance, and closely monitored in ICU to ensure that caspofungin is well tolerated via the inhaled route, and to provide data supporting the proposed administration scheme for part 2. * the first two patients (included one by one) will receive two aerosols (5 mg) during the first week, four days apart on d-1 and d-5 (level 1); * the third and fourth will receive two aerosols (15 mg) during the first week, four days apart on d-1 and d-5 (level 2); * the fifth and sixth will receive two aerosols (50 mg) during the first week, four days apart on d-1 and d-5 (level 3); * the seventh and eighth patients will receive four aerosols (50 mg) two days apart during one week, at d-1, then d-3, d-5 and d-7 (level 4); * the last two patients will have daily aerosols during the first week, from d-1 to d-7 (level 5) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male and female ≥18 years
- Medical management of Pneumocystis pneumonia based on :
- Person affiliated to a French social security system or equivalent
- Written informed consent obtained from the participant or, if the patient is not able to give consent from representative (trusted person, family member) or if the delay in obtaining the consent is assumed not compatible with the enrollment requirements, a temporary approval can be obtained from the investigator. In all cases, the patient's written informed consent will have to be obtained as soon as possible.
- Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship). Pregnancy test to be performed in all women from 15 to 45 years old who have not had an ovariectomy.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caspofungin Acetate 50 MGThe experimental treatment will be administered once daily for up to seven days, through the nebulization route by the means of a disposable vibrating mesh Aeroneb solo® nebulizer with the valved mask (Galway, Ireland). Before generating aerosol, resuspension of the caspofungin powder will be carried out in the same manner than for the IV route, into 10.5 mL saline serum. Preparation of the experimental drug (re-suspension) will be unblindly carried out in a distinct medical office by a nurse neither involved in the healthcare of the included patients, nor in the other parts of the study, data recording or outcome assessment. Once reconstituted, the suspension is expected to be limpid, with neither odour nor foam. Thereafter, its administration will be blindly completed by the clinical staff in charge of the enrolled patient. | Drug | Part 1 - open study, Part 2 - randomized study (group 1) |
| Physiologic salineProcedures will be exactly the same than those described above for the experimental group, but caspofungin will be replaced during the seven days of intervention by 10mL of 0.9% saline nebulized in the control group for a 15 minute-long process of nebulization (from d-1 to d-7). | Drug | Part 2 - randomized study (group 2) |
Primary outcome
Part 1: safety of inhaled caspofungin
Time frame: D-7 (day-7)
* frequency of adverse events * severity of adverse events
Part 2: proportion of patients alive and with a favorable clinical course* at the seventh day (day-7) after the first administration.
Time frame: D7 (day-7)
Composite outcome defined by at least one of the two following items persisting ≥24 hours in alive patients: * Relative reduction (de-escalation or withdrawal) of respiratory assistance due to clinical improvement (depending on the initial support): * extubation, or * weaning of non-invasive ventilatory support, or * weaning of nasal high-flow or low-flow oxygen therapy; (NB: all participating centers will implement uniform protocols for ventilatory assistance weaning) * Occurrence of a +50% increase in oxygenation (PaO2 / FiO2 ratio vs. the worst value observed after inclusion).
6 secondary outcomes
Individual components of the composite primary outcome at day-7 (d-7)
Time frame: D7 (day-7)
Safety of nebulized caspofungin in patients with Pneumocystis pneumonia through
Time frame: day-1 (d-1), d-2, d-3, d-4, d-5, d-6, and d-7
Pharmacokinetics of nebulized caspofungin
Time frame: 0, 2, 4, 6, 12, 24 hours, plus residual concentration at day (d-3) and d-7
Mortality
Time frame: day-28 (d-28) and d-90
Morbidity
Time frame: day-1 (d-1), d-7 and d-21
Pulmonary and systemic markers of lung infection (to assess the fungal clearance)
Time frame: day-1 (d-1), d-3, d-7, d-28 and d-90
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Results publication: PubMed 9872631Limper AH. Alveolar macrophage and glycoprotein responses to Pneumocystis carinii. Semin Respir Infect. 1998 Dec;13(4):339-47.
- Results publication: PubMed 22548840McKinnell JA, Cannella AP, Kunz DF, Hook EW 3rd, Moser SA, Miller LG, Baddley JW, Pappas PG. Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected persons. Transpl Infect Dis. 2012 Oct;14(5):510-8. doi: 10.1111/j.1399-3062.2012.00739.x. Epub 2012 May 1.
- Results publication: PubMed 23940606Lobo ML, Esteves F, de Sousa B, Cardoso F, Cushion MT, Antunes F, Matos O. Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for pneumocystis pneumonia: a pilot study in mice. PLoS One. 2013 Aug 5;8(8):e70619. doi: 10.1371/journal.pone.0070619. Print 2013.
- Results publication: PubMed 16304338Wong-Beringer A, Lambros MP, Beringer PM, Johnson DL. Suitability of caspofungin for aerosol delivery: physicochemical profiling and nebulizer choice. Chest. 2005 Nov;128(5):3711-6. doi: 10.1378/chest.128.5.3711.
- Results publication: PubMed 18046534Ehrmann S, Mercier E, Vecellio L, Ternant D, Paintaud G, Dequin PF. Pharmacokinetics of high-dose nebulized amikacin in mechanically ventilated healthy subjects. Intensive Care Med. 2008 Apr;34(4):755-62. doi: 10.1007/s00134-007-0935-1. Epub 2007 Nov 29.
- Results publication: PubMed 30776290Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019.0555.
- Results publication: PubMed 32194238Desoubeaux G, Lemaignen A, Ehrmann S. Scientific rationale for inhaled caspofungin to treat Pneumocystis pneumonia: A therapeutic innovation likely relevant to investigate in a near future.... Int J Infect Dis. 2020 Jun;95:464-467. doi: 10.1016/j.ijid.2020.03.029. Epub 2020 Mar 16. No abstract available.
- Results publication: PubMed 31633150Le Gal S, Toubas D, Totet A, Dalle F, Abou Bacar A, Le Meur Y, Nevez G; Anofel Association. Pneumocystis Infection Outbreaks in Organ Transplantation Units in France: A Nation-Wide Survey. Clin Infect Dis. 2020 May 6;70(10):2216-2220. doi: 10.1093/cid/ciz901.
- Results publication: PubMed 26935726Desoubeaux G, Dominique M, Morio F, Thepault RA, Franck-Martel C, Tellier AC, Ferrandiere M, Hennequin C, Bernard L, Salame E, Bailly E, Chandenier J. Epidemiological Outbreaks of Pneumocystis jirovecii Pneumonia Are Not Limited to Kidney Transplant Recipients: Genotyping Confirms Common Source of Transmission in a Liver Transplantation Unit. J Clin Microbiol. 2016 May;54(5):1314-20. doi: 10.1128/JCM.00133-16. Epub 2016 Mar 2.
- Results publication: PubMed 20946413Alanio A, Desoubeaux G, Sarfati C, Hamane S, Bergeron A, Azoulay E, Molina JM, Derouin F, Menotti J. Real-time PCR assay-based strategy for differentiation between active Pneumocystis jirovecii pneumonia and colonization in immunocompromised patients. Clin Microbiol Infect. 2011 Oct;17(10):1531-7. doi: 10.1111/j.1469-0691.2010.03400.x. Epub 2011 Apr 12.
- Results publication: PubMed 31548210Nevez G, Le Gal S. Caspofungin and Pneumocystis Pneumonia: It Is Time To Go Ahead. Antimicrob Agents Chemother. 2019 Sep 23;63(10):e01296-19. doi: 10.1128/AAC.01296-19. Print 2019 Oct. No abstract available.
- Derived from this study: PubMed 41151592Peghin M, Fishman JA, Grossi PA. Pneumocystis jiroveci : still troublesome to diagnose and treat. Curr Opin Infect Dis. 2025 Dec 1;38(6):522-529. doi: 10.1097/QCO.0000000000001155. Epub 2025 Oct 17.
- Supplier of the deviceLink provided by the sponsor.
- Supplier of the drugLink provided by the sponsor.
- Supplier of the diagnostic kitLink provided by the sponsor.
- Supplier of the diagnostic kitLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All research data can be requested
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Guillaume DESOUBEAUX, Prof study director
University Hospital of TOURS
Stephan EHRMANN, Prof study director
University Hospital of TOURS
Adrien LEMAIGNEN, Dr study director
University Hospital of TOURS
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Caspofungin Acetate 50 MG and Physiologic saline in people with Pneumocystis Pneumonia and Pneumocystis Jirovecii Infection, run by University Hospital, Tours at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guillaume DESOUBEAUX, Prof (+33(0)2 34 37 89 26, guillaume.desoubeaux@univ-tours.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: safety of inhaled caspofungin (time frame: D-7 (day-7)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06892951, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.