Status Acronym ISRCTN EUCT NCT (clinicaltrials.gov) DRKS
Active MR907-2502 2024-519575-26-00 NCT06794554

A phase 2, multicentre, open-label, single arm study to evaluate the effectiveness and safety of rezafungin (as acetate) in the treatment of chronic pulmonary aspergillosis (CPA) in patients with limited treatment options

Purpose / Objectives

Primary Outcome

To evaluate the effectiveness of 6 months’ rezafungin in the treatment of chronic pulmonary aspergillosis in subjects with limited treatment options according to clinical and radiological response as measured by the St George's Respiratory Questionnaire, weight, and CT imaging

Secondary Outcomes

  • Change in Aspergillus IgG levels at 3 and 6 months from baseline,
  • Change in St George’s Respiratory questionnaire score at 3 and 6 months from baseline,
  • Change in Respiratory Symptom Score at 3 and 6 months from baseline,
  • Change in EQ-5D-5L score at 3 and 6 months from baseline,
  • Change in weight at 3 and 6 months from baseline,
  • Need for a change in antibiotic or steroid prescription,
  • Absence of persistently positive respiratory sample for Aspergillus spp.,
  • Change in frequency of echinocandin resistant isolates,
  • Hospitalisations attributed to deterioration in any category.

 

Safety and tolerability of up to 6 months’ treatment with rezafungin; this will be assessed by nature and severity of AEs and SAEs, physical examinations and laboratory tests at 3 and 6 months.

Diagnosis

  • Chronic pulmonary aspergillosis

Target population

Age

18-99

Inclusion criteria

<!-- [if !supportLists]-->1.    <!--[endif]-->Willing and able to provide written informed consent.

<!-- [if !supportLists]-->2.    <!--[endif]-->Males or females ≥18 years of age

<!-- [if !supportLists]-->3.    <!--[endif]-->Established diagnosis of CPA according to ESCMID/ERS criteria (2016) which includes all the following, which should be present for ≥3 months:

<!-- [if !supportLists]-->o    <!--[endif]-->one or more clinical symptoms (persistent cough, recurrent haemoptysis, weight loss, malaise, night sweats, fever and dyspnoea)

<!-- [if !supportLists]-->o    <!--[endif]-->slowly progressive or persistent radiological findings (one or more cavities and surrounding fibrosis, infiltrates, consolidation, with or without fungal ball or progressive pleural thickening) on computed tomography (CT) of the thorax

<!-- [if !supportLists]-->o    <!--[endif]-->immunological, microbiological or molecular evidence of Aspergillus infection (growth of Aspergillus in respiratory secretions or serum galactomannan index >0.5 or BALF galactomannan index >1), positive Aspergillus IgG, or positive PCR

<!-- [if !supportLists]-->o    <!--[endif]-->exclusion of active tuberculosis or non-tuberculous mycobacterial pulmonary infection or disorders that will prevent evaluation of outcome over 6 months. Patients on anti- mycobacterial therapy can be enrolled if their mycobacterial infection is stabilised.

<!-- [if !supportLists]-->4.    <!--[endif]-->Subjects must be unable to receive systemic azole antifungal therapy due to any of the following: documented or anticipated resistance, intolerance, contraindication (e.g. due to drug-drug interactions or organ dysfunction), inability to take oral medication, or lack of availability. NOTE: the administration of rezafungin is monotherapy only, and subjects currently on azoles who are able to remain on therapy are not eligible

<!-- [if !supportLists]-->5.    <!--[endif]-->Antifungal treatment is indicated according to the opinion of the investigator due to radiological changes consistent with CPA progression OR high burden of symptoms

<!-- [if !supportLists]-->6.    <!--[endif]-->Female subjects of child-bearing potential <2 years post-menopausal (unless surgically sterile) must agree to and comply with using one barrier method (e.g., female condom with spermicide) plus one other highly effectivemethod of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence (only possible if it corresponds to the subject's usual lifestyle) while participating in this study, and for 30 days after the last dose of study drug. Male subjects must be vasectomized, abstain from heterosexual intercourse, or agree to use barrier contraception (condom with spermicide), and agree not to donate sperm while participating in the study and for 120 days from the last IV dose of study drug, unless the partner is >2 years post-menopausal or otherwise sterile.

<!-- [if !supportLists]-->o    <!--[endif]-->Definitions: Woman of childbearing potential: fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

<!-- [if !supportLists]-->o   <!--[endif]-->A postmenopausal state: no menses for 12 months without an alternative medical cause.

<!-- [if !supportLists]-->o   <!--[endif]-->Abstinence: refraining from heterosexual intercourse (only if it corresponds to the subject's usual lifestyle)

7.    <!--[endif]-->Willingness to comply with all aspects and assessments required in this study

Exclusion criteria

  1.  <!--[endif]-->Subjects with invasive aspergillosis, aspergillus nodules, or simple aspergilloma
  2. <!-- [if !supportLists]-->Known or suspected hypersensitivity to rezafungin for Injection or any of its excipients
  3. <!-- [if !supportLists]-->Current participation in another interventional treatment trial with an investigational agent. Participation in another interventional treatment trial is permitted during the follow-up period of the study
  4. <!-- [if !supportLists]-->Recent use of an investigational medicinal product within 28 days or 5 half-lives of the investigational medicinal product, whichever is greater, to prevent overlapping toxicities when this study’s investigational product is dosed, or presence of an investigational device at the time of screening. In some cases, use of investigational products may be acceptable in consultation with the Sponsor’s Medical Monitor
  5. <!-- [if !supportLists]-->Administration of any other echinocandin or intravenous antifungal treatment within 3 months of screening
  6. Administration of ≥15mg prednisolone daily (or other equivalent immunosuppressant) for at least 3 weeks within 4 weeks of screening OR a peripheral neutrophil count <0.5x109/L 
  7. <!-- [if !supportLists]-->Acute respiratory infections considered inadequately treated in the opinion of the Principal Investigator. Any subjects diagnosed with an acute respiratory infection during the screening period should be re-screened following the required course of appropriate treatment and enrolled when considered adequately treated.
  8. <!-- [if !supportLists]-->Subjects with active malignancy who are receiving chemotherapy or radiation therapy
  9. <!-- [if !supportLists]-->Subjects on the palliative care pathway
  10. <!--[endif]-->Any other condition or laboratory abnormality that, in the opinion of the Investigator, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study
  11. <!-- [if !supportLists]-->A. Meets National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, criteria for ataxia, tremor, motor neuropathy, or sensory neuropathy of Grade 2 or higher
    B.  <!--[endif]-->History of severe ataxia, tremor, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson’s Disease or Huntington’s Disease
  12. Planned or ongoing therapy at Screening with a known severe neurotoxic medication or with a known moderate neurotoxic medication in a patient with ataxia, tremor, motor neuropathy, or sensory neuropathy of CTCAE version 5.0 Grade 1 or higher
  13. <!-- [if !supportLists]-->Pregnant or lactating females

Study design

  • Phase II
  • Multicenter
  • Prospective
  • Tumor Biology, Infection and Immunity
  • One-arm
  • Open Label

Intervention

Providing all eligibility criteria are met, subjects will be enrolled on to the study and will receive a weekly IV infusion of rezafungin. After completion of 26 weeks (6 months) of treatment, subjects should return for an End of Treatment (EOT) visit 1 week after their last study drug administration and then a follow-up visit at week 30.

 

Documents (password protected)

Responsibilities in overall study

Sponsor

Mundipharma GmbH

(National) Coordinating Investigator

Dr. Chris Kosmidis