COVID-19 PneumoniaPhase 1NCT04460105
Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia
A Phase 1 study testing Lanadelumab in people with COVID-19 Pneumonia, run by Shire.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Pneumonia
- What is being tested?
- Lanadelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 31 Oct 2020to 27 Jan 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
About this study
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
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.
Read the 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.
- Conditions
- COVID-19 Pneumonia
- Being tested
- Lanadelumab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LanadelumabDrug
Also called SHP643, TAK-743, DX-2930
Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4.
PlaceboOther
Participants will receive placebo matching IV infusion on Day 1 and Day 4.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From start of study drug administration to follow-up (up to Day 29)
Secondary outcomes (4)
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.
Measured: 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)
Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.
Measured: 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)
Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.
Measured: 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)
Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start31 Oct 2020 (estimated)
- Primary completion27 Jan 2021 (estimated)
- Study completion27 Jan 2021 (estimated)
Why it stopped: Study was withdrawn due to challenges in site recruitment and lack of patient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19 PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda Development Center Americas, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04460105
- Sponsor's protocol ID
- TAK-743-1002
- Status last verified
- Oct 2020
- First submitted
- 30 Jun 2020
- Last updated
- 12 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04460105
- Acronym / sponsor ID
- TAK-743-1002
- Conditions
- COVID-19 Pneumonia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was withdrawn due to challenges in site recruitment and lack of patient enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 31 Oct 2020 (estimated)
- Primary completion
- 27 Jan 2021 (estimated)
- Study completion
- 27 Jan 2021 (estimated)
- First posted
- 7 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lanadelumab | Experimental | Drug: LanadelumabParticipants 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). |
| Placebo | Placebo comparator | Other: PlaceboParticipants 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LanadelumabAlso: SHP643, TAK-743, DX-2930Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4. | Drug | Lanadelumab |
| PlaceboParticipants will receive placebo matching IV infusion on Day 1 and Day 4. | Other | Placebo |
Primary outcome
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.
4 secondary outcomes
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
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 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 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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2020.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda Development Center Americas, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lanadelumab in people with COVID-19 Pneumonia, run by Shire.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 12 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Treatment emergent adverse events (TEAEs) (time frame: From start of study drug administration to follow-up (up to Day 29)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2020.