Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

• ClinicalTrials.gov Identifier: NCT04848272
• Recruitment Status: Active, not recruiting
• First Posted: April 19, 2021
• Last Update Posted: April 17, 2024
• Sponsor: St Vincent's Institute of Medical Research
• Information provided by (Responsible Party): Duncan Campbell, St Vincent's Institute of Medical Research

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Lung Injury	Drug: Lanadelumab; Other: Saline control	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: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open-label placebo-controlled dose-escalation Phase 1 study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury
• Actual Study Start Date: August 9, 2021
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

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 Name: Takhzyro
Experimental: Lanadelumab 100 mg; Lanadelumab 100 mg	Drug: Lanadelumab; Monoclonal antibody that targets active plasma kallikrein; Other Name: Takhzyro
Experimental: Lanadelumab 300 mg; Lanadelumab 300 mg	Drug: Lanadelumab; Monoclonal antibody that targets active plasma kallikrein; Other Name: Takhzyro

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Related Adverse Events [ Time Frame: 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 [ Time Frame: 0, 6, 12, and 24 hours ]
   Blood bradykinin concentration

Eligibility Criteria

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

Criteria

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

Locations

Australia, Victoria

St Vincent's Hospital Melbourne

Melbourne, Victoria, Australia, 3065

Sponsors and Collaborators

St Vincent's Institute of Medical Research

More Information

• Responsible Party: Duncan Campbell, Associate Professor, St Vincent's Institute of Medical Research
• ClinicalTrials.gov Identifier: NCT04848272
• Other Study ID Numbers: SVI-01
• First Posted: April 19, 2021
• Last Update Posted: April 17, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymised individual participant data (IPD) available to other researchers
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: After completion of study
• Access Criteria: To be determined

• 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

Additional relevant MeSH terms:

Lung Injury; Wounds and Injuries; Lung Diseases; Respiratory Tract Diseases; Thoracic Injuries