Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

NCT04848272 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: SVI-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Lung Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Blood bradykinin concentration

  0, 6, 12, and 24 hours

Study Arms (4)

Saline control

PLACEBO COMPARATOR

Saline control

Other: Saline control

Lanadelumab 30 mg

EXPERIMENTAL

Lanadelumab 30 mg

Drug: Lanadelumab

Lanadelumab 100 mg

EXPERIMENTAL

Lanadelumab 100 mg

Drug: Lanadelumab

Lanadelumab 300 mg

EXPERIMENTAL

Lanadelumab 300 mg

Drug: Lanadelumab

Interventions

Lanadelumab DRUG

Monoclonal antibody that targets active plasma kallikrein

Also known as: Takhzyro

Lanadelumab 100 mg; Lanadelumab 30 mg; Lanadelumab 300 mg

Saline control OTHER

Saline control

Saline control

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St Vincent's Institute of Medical Research: lead

Study Sites (1)

St Vincent's Hospital Melbourne

Melbourne, Victoria, 3065, Australia

Location

MeSH Terms

Conditions

Lung Injury

Interventions

lanadelumab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Open-label placebo-controlled dose-escalation Phase 1 study

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 19, 2021
• Study Start: August 9, 2021
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After completion of study
• Access Criteria: To be determined

Locations

AU (1)