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Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

Primary Purpose

Lung Injury

Status

Recruiting

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

Lanadelumab

Saline control

About this trial

This is an interventional treatment trial for Lung Injury

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

St Vincent's Hospital MelbourneRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Saline control

Lanadelumab 30 mg

Lanadelumab 100 mg

Lanadelumab 300 mg

Arm Description

Saline control

Lanadelumab 30 mg

Lanadelumab 100 mg

Lanadelumab 300 mg

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Blood bradykinin concentration

Full Information

NCT ID

NCT04848272

First Posted

April 13, 2021

Last Updated

May 4, 2022

Sponsor

St Vincent's Institute of Medical Research

1. Study Identification

Unique Protocol Identification Number

NCT04848272

Brief Title

Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

Official Title

Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

August 9, 2021 (Actual)

Primary Completion Date

December 2022 (Anticipated)

Study Completion Date

June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

St Vincent's Institute of Medical Research

4. Oversight

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.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

Detailed Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Open-label placebo-controlled dose-escalation Phase 1 study

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Saline control

Arm Type

Placebo Comparator

Arm Description

Saline control

Arm Title

Lanadelumab 30 mg

Arm Type

Experimental

Arm Description

Lanadelumab 30 mg

Arm Title

Lanadelumab 100 mg

Arm Type

Experimental

Arm Description

Lanadelumab 100 mg

Arm Title

Lanadelumab 300 mg

Arm Type

Experimental

Arm Description

Lanadelumab 300 mg

Intervention Type

Drug

Intervention Name(s)

Lanadelumab

Other Intervention Name(s)

Takhzyro

Intervention Description

Monoclonal antibody that targets active plasma kallikrein

Intervention Type

Other

Intervention Name(s)

Saline control

Intervention Description

Saline control

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Related Adverse Events

Description

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Blood bradykinin concentration

Description

Blood bradykinin concentration

Time Frame

0, 6, 12, and 24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility 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.

Facility Information:

Facility Name

St Vincent's Hospital Melbourne

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3065

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Duncan J Campbell, MB.BS., PhD

Phone

61 429959601

dcampbell@svi.edu.au

First Name & Middle Initial & Last Name & Degree

Barry Dixon, MB.BS., PhD

Phone

61 439618815

barry.dixon@svha.org.au

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

Learn more about this trial

Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

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