COVID-19 PneumoniaPhase 3NCT04901689
Leronlimab in Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation
A Phase 3 study testing Leronlimab in people with COVID-19 Pneumonia, run by Hospital Israelita Albert Einstein at 23 sites in Brazil.
Trial summary
Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). Disruption of the C-C chemokine ligand 5 (CCL5)-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune… 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?
- Leronlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 316 participants
- Where
- 23 sitesBrazil
- Study dates
- 23 Oct 2021to Feb 2023
- Phase
- Phase 3
- 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
- Male or females aged ≥ 18 years
- Critically ill patients with COVID-19 (defined as Ordinal Scale score of 7): Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for less than 72 hours.
- Evidence of pneumonia (pulmonary infiltrates) at chest radiography or computed tomography compatible with COVID-19.
- Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR).
- Subject (or legally authorized representative) provides written or oral informed consent prior to initiation of any study procedures.
- Women of childbearing potential and their partner must agree to use at least one highly effective method of contraception (e.g., hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices, bilateral tubal occlusion, or sexual abstinence) for the duration of the study.
Who cannot join
- Subjects who had been on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for >72 hours prior to the screening.
- Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
- Inability to provide informed consent (from subject or legally authorized representative) or to comply with test requirements.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk associated with study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Pregnancy or breast feeding.
- Subject participating in another study with for an investigational treatment.
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- Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of COVID-19), that may increase the risk for the study participant based on investigator judgement.
- Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (e.g., azathioprine, cyclosporine).
- Patients with estimated discharge or transfer for other hospital in the first 72 hours of study inclusion.
- Patients with low probability of survival in the first 48 hours of study inclusion.
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Brazil23 sites
Centro de Pesquisa Clínica do Coração
Aracaju, Sergipe
Fundação PIO XII
Barretos, São Paulo
Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista
Bragança Paulista, São Paulo
Hospital do Coração do Brasil
Brasília, Federal District
Instituto de Pesquisa Clínica de Campinas
Campinas, São Paulo
Hospital Santa Ignes
Indaiatuba, São Paulo
Clinica São Roque
Ipiaú, Estado de Bahia
Hospital Dr Jayme dos Santos Neves
Laranjeiras, Espírito Santo
Instituto Atena de Pesquisa Clínica
Natal, Rio Grande do Norte
Hospital São Vicente de Paulo
Passo Fundo, Rio Grande do Sul
Santa Casa de Misericórdia de Passos
Passos, Minas Gerais
Hospital Mãe de Deus
Porto Alegre, Rio Grande do Sul
Irmandade da Santa Casa de Misericórdia Porto Alegre
Porto Alegre, Rio Grande do Sul
Hospital São Lucas Copacabana
Rio de Janeiro, Rio de Janeiro
Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
Salvador, Estado de Bahia
Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José do Rio Preto, São Paulo
Hospital 9 de Julho
São Paulo, Please Select
BP Mirante
São Paulo, São Paulo
Hospital Alemão Oswaldo Cruz
São Paulo, São Paulo
Hospital Beneficência Portuguesa
São Paulo, São Paulo
Hospital Israelita Albert Einstein
São Paulo
Hospital M'Boi Mirim
São Paulo
Santa Casa de Votuporanga
Votuporanga, São Paulo
About this study
Official title: A Phase 3, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Leronlimab in Combination With Standard of Care for Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation
Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). Disruption of the C-C chemokine ligand 5 (CCL5)-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in coronavirus disease 2019 (COVID-19).
The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).
Read the detailed description
Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). CCR5 is expressed predominantly on T cells but also found on macrophages, dendritic cells, and eosinophils to mediate chemotaxis in response to its cognate ligands that include CCL5 (RANTES), CCL3 (MIP-1α), and CCL4 (MIP-1β). These ligands are integral in the recruitment of these immune cells to inflammatory sites. The immunopathogenesis of COVID-19 likely involves the excessive influx of immune cells into the lung. Disruption of the CCL5-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in COVID-19.
The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).
This is a Phase 3, 2-arm, randomized, double blind, placebo controlled, multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) as an add on therapy to the institutional standard of care (SoC) for the management of critically ill patients with COVID-19 pneumonia.
Patients will be randomized in a 1:1 ratio to receive up to four doses of 700 mg leronlimab (PRO 140) or placebo. Leronlimab or placebo will be administered by 30-minute intravenous (IV) infusion weekly over a 4-week treatment period. No treatments will be administered post-discharge.
The participant will be evaluated on each study day while hospitalized up until and including Day 28. The daily visits will capture clinical status - ordinal scale and the occurrence of adverse events. A complete follow-up assessment will be performed at Days 7, 14, 21, 28, 42 and 60 for those who are hospitalized at these specific timepoints. Follow-up visits can be conducted as telephone or video contact visits, if subject is discharged from the hospital prior to the complete follow-up visits.
- Conditions
- COVID-19 Pneumonia
- Being tested
- Leronlimab, Placebo
- Keywords
- COVID-19, Pneumonia, Leronlimab
- Medical subject headings
- COVID-19, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeronlimabDrug
Leronlimab 700 mg
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Leronlimab (700 mg) | Experimental | Leronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge Receives: Drug: Leronlimab |
| Placebo | Placebo comparator | Placebo intravenously once a week (up to 4 doses) until hospital discharge Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative proportion of clinical recovery
Patients will be considered to have recovered if they attain categories 1, 2, or 3 on the eight-category ordinal scale within 28 days, as follows:
- Not hospitalized, no limitations on activities
- Not hospitalized, limitation on activities and/or requiring home oxygen
- Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
- Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
- Hospitalized, requiring supplemental oxygen
- Hospitalized, on non-invasive ventilation or high flow oxygen devices
- Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
- Death
Measured: 28 days
Secondary outcomes (7)
Proportion of patients clinically recovered
Ordinal Scale of 1, 2 or 3
Measured: At days 14, 28, 42, and 60
All-cause mortality
All-cause mortality
Measured: At days 14, 28, 42, and 60
Proportion of patients discharged alive
Ordinal Scale 1 or 2
Measured: At days 14, 28, 42, and 60
Clinical Status
Ordinal Scale
Measured: Days 14, 28, 42, and 60
Duration of invasive mechanical ventilation or ECMO
Days
Measured: 28 days
Length of hospital stay
Days
Measured: 28 days
Length of ICU stay
Days
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2021
- Study start23 Oct 2021
- Primary completionFeb 2023 (estimated)
- Study completionFeb 2023 (estimated)
Why it stopped: Pending DSMB evaluation
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 316 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Israelita Albert Einstein
- Sponsor type
- University, hospital or other
- Collaborators
- CytoDyn, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04901689
- Sponsor's protocol ID
- ARO_21_018_002
- Status last verified
- May 2021
- First submitted
- 24 May 2021
- Last updated
- 15 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Leronlimab in Combination With Standard of Care for Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation
- ClinicalTrials.gov ID
- NCT04901689
- Acronym / sponsor ID
- ARO_21_018_002
- Conditions
- COVID-19 Pneumonia
- Keywords
- COVID-19, Pneumonia, Leronlimab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Pending DSMB evaluation
- Enrolment
- 316 participants (estimated)
- Lead sponsor
- Hospital Israelita Albert EinsteinUniversity, hospital or other
- Collaborators
- CytoDyn, Inc.
- Study start
- 23 Oct 2021 (actual)
- Primary completion
- Feb 2023 (estimated)
- Study completion
- Feb 2023 (estimated)
- First posted
- 25 May 2021 (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.
Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). Disruption of the C-C chemokine ligand 5 (CCL5)-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in coronavirus disease 2019 (COVID-19).
The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).
Detailed description
Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). CCR5 is expressed predominantly on T cells but also found on macrophages, dendritic cells, and eosinophils to mediate chemotaxis in response to its cognate ligands that include CCL5 (RANTES), CCL3 (MIP-1α), and CCL4 (MIP-1β). These ligands are integral in the recruitment of these immune cells to inflammatory sites. The immunopathogenesis of COVID-19 likely involves the excessive influx of immune cells into the lung. Disruption of the CCL5-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in COVID-19.
The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).
This is a Phase 3, 2-arm, randomized, double blind, placebo controlled, multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) as an add on therapy to the institutional standard of care (SoC) for the management of critically ill patients with COVID-19 pneumonia.
Patients will be randomized in a 1:1 ratio to receive up to four doses of 700 mg leronlimab (PRO 140) or placebo. Leronlimab or placebo will be administered by 30-minute intravenous (IV) infusion weekly over a 4-week treatment period. No treatments will be administered post-discharge.
The participant will be evaluated on each study day while hospitalized up until and including Day 28. The daily visits will capture clinical status - ordinal scale and the occurrence of adverse events. A complete follow-up assessment will be performed at Days 7, 14, 21, 28, 42 and 60 for those who are hospitalized at these specific timepoints. Follow-up visits can be conducted as telephone or video contact visits, if subject is discharged from the hospital prior to the complete follow-up visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Leronlimab (700 mg) | Experimental | Drug: LeronlimabLeronlimab 700 mg intravenously once a week (up to 4 doses) until hospital discharge |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo intravenously once a week (up to 4 doses) until hospital discharge |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or females aged ≥ 18 years
- Critically ill patients with COVID-19 (defined as Ordinal Scale score of 7): Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for less than 72 hours.
- Evidence of pneumonia (pulmonary infiltrates) at chest radiography or computed tomography compatible with COVID-19.
- Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR).
- Subject (or legally authorized representative) provides written or oral informed consent prior to initiation of any study procedures.
Key exclusion criteria (10 listed)
- Subjects who had been on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) for >72 hours prior to the screening.
- Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
- Inability to provide informed consent (from subject or legally authorized representative) or to comply with test requirements.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk associated with study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Pregnancy or breast feeding.
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 |
|---|---|---|
| LeronlimabLeronlimab 700 mg | Drug | Leronlimab (700 mg) |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Cumulative proportion of clinical recovery
Time frame: 28 days
Patients will be considered to have recovered if they attain categories 1, 2, or 3 on the eight-category ordinal scale within 28 days, as follows: 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities and/or requiring home oxygen 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 5. Hospitalized, requiring supplemental oxygen 6. Hospitalized, on non-invasive ventilation or high flow oxygen devices 7. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 8. Death
7 secondary outcomes
Proportion of patients clinically recovered
Time frame: At days 14, 28, 42, and 60
All-cause mortality
Time frame: At days 14, 28, 42, and 60
Proportion of patients discharged alive
Time frame: At days 14, 28, 42, and 60
Clinical Status
Time frame: Days 14, 28, 42, and 60
Duration of invasive mechanical ventilation or ECMO
Time frame: 28 days
Length of hospital stay
Time frame: 28 days
Length of ICU stay
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2022.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Leronlimab in people with COVID-19 Pneumonia, run by Hospital Israelita Albert Einstein at 23 sites in Brazil.
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 10 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: paused, as of the sponsor's last update on 15 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Cumulative proportion of clinical recovery (time frame: 28 days). 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 15 Apr 2022.