Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia
Primary Purpose
COVID-19 Pneumonia
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Lanadelumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 Pneumonia
Eligibility 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:
- 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
- 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:
- Hemoglobin <= 8 grams per deciliter (g/dL)
- White blood cells <= 3000/ microliters (μL)
- Platelets <= 75,000/μL
- 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)
- 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).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Lanadelumab
Placebo
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
Number of Participants with Treatment emergent adverse events (TEAEs)
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
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.
Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)
Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.
Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)
Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.
Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)
Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.
Full Information
NCT ID
NCT04460105
First Posted
June 30, 2020
Last Updated
October 9, 2020
Sponsor
Shire
Collaborators
Takeda Development Center Americas, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04460105
Brief Title
Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Study was withdrawn due to challenges in site recruitment and lack of patient enrollment
Study Start Date
October 31, 2020 (Anticipated)
Primary Completion Date
January 27, 2021 (Anticipated)
Study Completion Date
January 27, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
Collaborators
Takeda Development Center Americas, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lanadelumab
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Lanadelumab
Other Intervention Name(s)
SHP643, TAK-743, DX-2930
Intervention Description
Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Participants will receive placebo matching IV infusion on Day 1 and Day 4.
Primary Outcome Measure Information:
Title
Number of Participants with Treatment emergent adverse events (TEAEs)
Description
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.
Time Frame
From start of study drug administration to follow-up (up to Day 29)
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
Description
Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.
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
Title
Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)
Description
Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.
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
Title
Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)
Description
Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.
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
Title
Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)
Description
Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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
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:
Hemoglobin <= 8 grams per deciliter (g/dL)
White blood cells <= 3000/ microliters (μL)
Platelets <= 75,000/μL
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)
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda Development Center Americas, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Learn more about this trial
Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia
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