Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

St Vincent's Institute of Medical Research (Other)
Overall Status
Recruiting ID

Study Details

Study Description

Brief Summary

Phase 1 study investigating safety of lanadelumab administration to patients with lung injury

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This study will investigate the safety of inhibition of plasma kallikrein by lanadelumab administration in patients with lung injury.

Study Design

Study Type:
Anticipated Enrollment :
48 participants
Intervention Model:
Sequential Assignment
Intervention Model Description:
Open-label placebo-controlled dose-escalation Phase 1 studyOpen-label placebo-controlled dose-escalation Phase 1 study
None (Open Label)
Primary Purpose:
Official Title:
Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury
Actual Study Start Date :
Aug 9, 2021
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Saline control

Saline control

Other: Saline control
Saline control

Experimental: Lanadelumab 30 mg

Lanadelumab 30 mg

Drug: Lanadelumab
Monoclonal antibody that targets active plasma kallikrein
Other Names:
  • Takhzyro
  • Experimental: Lanadelumab 100 mg

    Lanadelumab 100 mg

    Drug: Lanadelumab
    Monoclonal antibody that targets active plasma kallikrein
    Other Names:
  • Takhzyro
  • Experimental: Lanadelumab 300 mg

    Lanadelumab 300 mg

    Drug: Lanadelumab
    Monoclonal antibody that targets active plasma kallikrein
    Other Names:
  • Takhzyro
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment-Related Adverse Events [28 days]

      Blood gases, pH, bicarbonate, carbon dioxide and lactic acid levels. If the participant is receiving mechanical ventilation, the ventilator settings will be constantly monitored. Chest X-ray, as indicated. Constant monitoring of haemodynamics (pulse rate, blood pressure) via an arterial cannula, use of vasoactive medications, and constant monitoring of ECG. Fluid balance, including urine output. Serum creatinine, electrolytes, liver function, creatinine kinase, FBE and coagulation will be measured daily or less frequently as decided by the treating team. If there is suspicion of infection, then appropriate samples will be taken for microbiological examination. Neurological function will be assessed several times per day.

    Secondary Outcome Measures

    1. Blood bradykinin concentration [0, 6, 12, and 24 hours]

      Blood bradykinin concentration

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years to 90 Years
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    • Age >18 years admitted to the ICU with primary diagnosis of lung injury. The criteria for the diagnosis of lung injury include five principal elements: hypoxemia (blood oxygen saturation (PaO2) ≤92% when breathing ambient air, ratio of PaO2 to the fraction of inspired oxygen (FiO2) ≤300), diffuse pulmonary infiltrates on chest radiographs, decreased lung compliance, and the absence of congestive heart failure.

    • Both males and females will be recruited in the proportion in which they are admitted to the ICU with lung injury.

    • Arterial cannula in place as part of usual care for the measurement of blood gases.

    • Patients may or may not be intubated and mechanically ventilated.

    • Able to provide informed consent, or if unable to do so, a responsible person:

    medical treatment decision maker is available (by telephone if necessary) who can be approached to seek consent.

    Exclusion Criteria:
    • Other causes of lung infiltrates: pulmonary oedema, alveolar haemorrhage, adverse drug reactions, radiation injury and the idiopathic pneumonitis syndrome.

    • Significant dysfunction of non-pulmonary organs in the opinion of the treating ICU consultant.

    • Death is deemed imminent or inevitable or there is underlying disease with a life expectancy of less than 90 days.

    • Previously enrolled in this study.

    • Enrolled in another study.

    • Usually receives home oxygen.

    • Usually receives any type of assisted ventilation at home. e.g. continuous positive airway pressure for obstructive sleep apnoea.

    • Pregnant or might be pregnant. Women aged 18 to 49 are excluded unless there is documented menopause, hysterectomy or surgical sterilisation, or a pregnancy test is negative.

    • Objection from the treating clinician.

    • Consent refused by the patient or substitute decision maker.

    Contacts and Locations


    Site City State Country Postal Code
    1 St Vincent's Hospital Melbourne Melbourne Victoria Australia 3065

    Sponsors and Collaborators

    • St Vincent's Institute of Medical Research


    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Duncan Campbell, Associate Professor, St Vincent's Institute of Medical Research Identifier:
    Other Study ID Numbers:
    • SVI-01
    First Posted:
    Apr 19, 2021
    Last Update Posted:
    May 6, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Product Manufactured in and Exported from the U.S.:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 6, 2022