Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia

NCT04460105 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: TAK-743-1002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

COVID-19 Pneumonia

Outcome Measures

Primary Outcomes (1)

• 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.

  From start of study drug administration to follow-up (up to Day 29)

Secondary Outcomes (4)

• Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab

  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

• Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)

  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 Cleaved High Molecular Weight Kininogen (cHMWK)

  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-Inhibitor (C1-INH)

  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

Study Arms (2)

Lanadelumab

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Lanadelumab DRUG

Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4.

Also known as: SHP643, TAK-743, DX-2930

Lanadelumab

Placebo OTHER

Participants will receive placebo matching IV infusion on Day 1 and Day 4.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

MeSH Terms

Interventions

lanadelumab

Study Officials

• Study Director

  Takeda Development Center Americas, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 7, 2020
• Study Start: October 31, 2020
• Primary Completion: January 27, 2021
• Study Completion: January 27, 2021
• Last Updated: October 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.