Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

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

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Injury
• Intervention / Treatment: Other: Saline control; Drug: Lanadelumab

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline control	Other: Saline control; Saline control
Experimental: Lanadelumab 30 mg	Drug: Lanadelumab; Monoclonal antibody that targets active plasma kallikrein; Other Names: Takhzyro
Experimental: Lanadelumab 100 mg	Drug: Lanadelumab; Monoclonal antibody that targets active plasma kallikrein; Other Names: Takhzyro
Experimental: Lanadelumab 300 mg	Drug: Lanadelumab; Monoclonal antibody that targets active plasma kallikrein; Other Names: Takhzyro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events	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.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood bradykinin concentration	Blood bradykinin concentration	0, 6, 12, and 24 hours

Collaborators and Investigators

• Sponsor: St Vincent's Institute of Medical Research

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Thoracic Injuries; Wounds and Injuries; Lung Injury
• Other Study ID Numbers: SVI-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised individual participant data (IPD) available to other researchers
• IPD Sharing Time Frame: After completion of study
• IPD Sharing Access Criteria: To be determined
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No