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Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04460105
Recruitment Status : Withdrawn (Study was withdrawn due to challenges in site recruitment and lack of patient enrollment)
First Posted : July 7, 2020
Last Update Posted : October 12, 2020
Sponsor:
Collaborator:
Takeda Development Center Americas, Inc.
Information provided by (Responsible Party):
Takeda ( Shire )

Brief Summary:
The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in adults hospitalized with COVID-19 pneumonia.

Condition or disease Intervention/treatment Phase
COVID-19 Pneumonia Drug: Lanadelumab Other: Placebo Phase 1

Detailed Description:
This study consists of two cohorts (Cohort 1 [Single-dose Cohort], and Cohort 2 [Repeat-dose Cohort]). Up to approximately 24 participants will be enrolled in this study, in which up to 12 participants may be enrolled into Cohort 1. However, Cohort 1 will be closed upon implementation of Amendment 2. Approximately 12 participants will be enrolled in Cohort 2. Participants will be randomized in 3:1 ratio (9 lanadelumab: 3 placebo) in each Cohort.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 Pneumonia
Estimated Study Start Date : October 31, 2020
Estimated Primary Completion Date : January 27, 2021
Estimated Study Completion Date : January 27, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Lanadelumab
Participants receive 300 milligram (mg) of lanadelumab intravenous (IV) infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).
Drug: Lanadelumab
Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4.
Other Names:
  • SHP643
  • TAK-743
  • DX-2930

Placebo Comparator: Placebo
Participants will receive placebo matching IV infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).
Other: Placebo
Participants will receive placebo matching IV infusion on Day 1 and Day 4.




Primary Outcome Measures :
  1. Number of Participants with Treatment emergent adverse events (TEAEs) [ Time Frame: From start of study drug administration to follow-up (up to Day 29) ]
    Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab [ Time Frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours post-dose ]
    Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.

  2. Percentage Change from Baseline in Plasma Kallikrein Activity (pKal) [ Time Frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose ]
    Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.

  3. Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK) [ Time Frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose ]
    Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.

  4. Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH) [ Time Frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose ]
    Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females 18 years of age or older at the time of signing of the informed consent form (ICF).
  • Hospitalized with evidence of COVID-19 pneumonia defined as:

    1. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection documented with polymerase chain reaction (PCR) of any specimen; e.g. respiratory, blood, urine, stool, other body fluid
    2. Presence of respiratory distress as indicated by peripheral capillary oxygen saturation (SpO2) lesser than or equal to (=<) 93 percent (%) on room air or respiratory rate greater than or equal to (>=) 30 breaths per minute (breaths/min).
  • The participant (or a legally acceptable representative) has provided written informed consent approved by the institutional review board (IRB)/ independent ethics committee (IEC) before any study-specific procedures are performed.
  • Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.

Exclusion Criteria:

  • Invasive mechanical ventilation (IMV) extracorporeal membrane oxygenation (ECMO) or with evidence of severe respiratory distress such that IMV/ECMO is imminent within 12 hours of randomization.
  • Where, in the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
  • Requiring vasopressor support (use of fluid support is not exclusionary)
  • Known or suspected venous thromboembolism.
  • Known or suspected hypersensitivity to lanadelumab or any of its excipients.
  • Dosing with an investigational drug or exposure to an investigational device within 4 weeks prior to screening.
  • Previous (within 3 months of screening) or current use of immunomodulators (e.g. methotrexate, azathioprine, 6-mercaptopurine, tumor necrosis factor [TNF] alpha inhibitor, Janus kinase [JAK] inhibitor, alpha-integrin).
  • Previous (within 3 months of screening) or current use of plasma kallikrein inhibitor or bradykinin receptor blocker.
  • Use of supplemental oxygen for a medical condition prior to receiving COVID-19 diagnosis.
  • Previously diagnosed with acquired immunodeficiency syndrome (AIDS).
  • Active tuberculosis or clinical suspicion of latent tuberculosis.
  • Any of the following laboratory abnormalities at screening:

    1. Hemoglobin <= 8 grams per deciliter (g/dL)
    2. White blood cells <= 3000/ microliters (μL)
    3. Platelets <= 75,000/μL
    4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 3×upper limit of normal (ULN); alkaline phosphatase (ALP) >= 3×ULN; or total bilirubin greater than (>) 2×ULN (unless the bilirubin elevation is a result of Gilbert's syndrome)
    5. Creatinine >= 2×ULN
  • Pregnant or breastfeeding.
  • Any significant condition (any surgical or medical condition) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (e.g. significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04460105


Sponsors and Collaborators
Shire
Takeda Development Center Americas, Inc.
Investigators
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Study Director: Study Director Takeda Development Center Americas (TDCA)
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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT04460105    
Other Study ID Numbers: TAK-743-1002
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: October 12, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections