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.
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.
Drug: Lanadelumab
Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4.
Other Name: Array
Other: Placebo
Participants will receive placebo matching IV infusion on Day 1 and Day 4.
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).
Cardiology Associates Research Company
Daytona Beach, Florida, 32117
Investigator: Site Contact
Contact: 386-677-6672
Investigator: David Henderson
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Investigator: Site Contact
Contact: 216-844-3201
Investigator: Rana Hejal
Study Director, Study Director
Takeda Development Center Americas, Inc.