Bevacizumab for Acute Respiratory Distress Syndrome

Recruiting at 3 trial locations

Overseen By Just Breathe Trial Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: PPD DEVELOPMENT, LP

Must not be taking: Aspirin, Clopidogrel, DOACs

Disqualifiers: Cirrhosis, Dialysis, Hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: In-hospital stay

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but it does mention that participants on anticoagulants must have stable doses for at least 2 weeks before starting the study. Also, certain medications like high-dose aspirin or specific anticoagulants without reversal agents may need to be stopped.

What is known about the safety of bevacizumab in humans?

Bevacizumab, used for treating various cancers, can cause side effects like bleeding, high blood pressure, and blood clots. Some serious but rare side effects include stroke and heart problems. These side effects are generally manageable with standard medical care. ^{1 2 3 4 5}

How is the drug Bevacizumab unique for treating acute respiratory distress syndrome (ARDS)?

Bevacizumab is unique for treating ARDS because it targets vascular endothelial growth factor (VEGF), which is involved in increasing lung permeability and edema (fluid buildup). Unlike other treatments, Bevacizumab may help reduce these effects by inhibiting VEGF, potentially stabilizing the lung's blood vessels and reducing fluid leakage. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Cohort C: Participants will be randomized to receive either a placebo or bevacizumab. This record describes the default procedures and analyses for Cohort C. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

Eligibility Criteria

This trial is for hospitalized adults with Acute Respiratory Distress Syndrome (ARDS). Participants must meet additional criteria not specified here to join. People who don't fit the inclusion criteria or meet any exclusion factors can't participate.

Inclusion Criteria

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Timeline

Screening

Participants are screened for eligibility to participate in the trial

<24 hours

Treatment

Participants receive either bevacizumab or placebo starting on Day 1 through discharge from the hospital

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment through the end of study

90 days

Treatment Details

Interventions

• Bevacizumab

Trial Overview The study compares two groups: one receiving bevacizumab and the other a placebo, in a randomized, double-blinded setup to ensure neither the participants nor the researchers know who gets which treatment until after the results are collected.

Participant Groups

Group I: Cohort C: bevacizumab Experimental Treatment 1 Intervention

Group II: Cohort C: placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

PPD DEVELOPMENT, LP

Lead Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD Development, LP

Lead Sponsor

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Edesa Biotech Inc.

Industry Sponsor

Trials

6

Recruited

2,100+

Biomedical Advanced Research and Development Authority BARDA (Funder)

Collaborator

Trials

4

Recruited

1,200+

InflaRx GmbH

Industry Sponsor

Trials

16

Recruited

2,300+

Founded

2007

Headquarters

Jena, Germany

Known For

Inflammation research

Top Products

Gohibic (vilobelimab)

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Bevacizumab therapy is associated with several adverse events, the most common being hypertension, which requires regular monitoring and management with antihypertensive medications during treatment.

Close monitoring for other serious complications, such as proteinuria and thromboembolic events, is crucial, as timely management can help prevent severe outcomes and improve patient safety throughout the course of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding and managing the possible adverse effects associated with bevacizumab. Shord, SS., Bressler, LR., Tierney, LA., et al.[2020]

A comprehensive analysis of 96,477 adverse event reports related to bevacizumab revealed 2,847 cases of hemorrhage, highlighting significant safety concerns associated with its use in treating advanced malignant tumors.

The study identified 37 specific hemorrhagic signals linked to bevacizumab, particularly affecting the vascular, gastrointestinal, and nervous systems, with colorectal, lung, and breast cancers being the most commonly associated malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacovigilance study of adverse event profiles and haemorrhagic safety of bevacizumab based on the FAERS database. Tang, L., Ding, C., Li, H., et al.[2023]

Bevacizumab, an antibody targeting VEGF, is effective for treating various cancers, including metastatic colon cancer and non-small-cell lung cancer, but it carries significant risks of severe side effects such as arterial thromboembolism and stroke.

The report highlights two fatal cases of arterial thromboembolic events in cancer patients treated with bevacizumab, emphasizing the need for careful monitoring and documentation of adverse effects associated with antiangiogenic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implication of bevacizumab in fatal arterial thromboembolic incidents. Grivas, AA., Trafalis, DT., Athanassiou, AE.[2015]

Bevacizumab, an angiogenesis inhibitor, is associated with serious and potentially life-threatening toxicities, including hemorrhage, gastrointestinal perforation, and hypertension, necessitating early recognition and management.

Patients with preexisting conditions such as hypertension or cardiovascular disease are at higher risk for these toxicities, highlighting the need for careful monitoring and tailored management strategies in oncology practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intricacies of bevacizumab-induced toxicities and their management. Gressett, SM., Shah, SR.[2022]

Bevacizumab, when combined with chemotherapy, significantly improves clinical outcomes and delays disease progression in patients with advanced non-squamous non-small-cell lung cancer (NSCLC), as demonstrated in pivotal phase III trials involving large patient populations.

The safety profile of bevacizumab is well-characterized, with manageable adverse events such as hypertension and bleeding, and the overall incidence of serious side effects is similar to that of placebo, indicating it can be safely administered in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging safety data for bevacizumab in advanced non-small-cell lung cancer. Hirsh, V.[2015]

In an in vitro study using A549 lung cells, exposure to acid significantly suppressed cell proliferation and VEGF production for at least 48 hours, indicating that acid can harm lung cells.

The addition of exogenous VEGF restored cell proliferation, and this effect was blocked by anti-VEGF antibodies, suggesting that VEGF plays a protective role in lung cell recovery after acid injury by interacting with its receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells. Ohwada, A., Yoshioka, Y., Iwabuchi, K., et al.[2020]

In a study using 80 male BALB/c mice, it was found that inhaling lipopolysaccharide (LPS) increased levels of vascular endothelial growth factor (VEGF), which is linked to lung injury in acute respiratory distress syndrome (ARDS).

Treatment with anti-VEGF using soluble fms-like tyrosine kinase-1 (sFlt-1) effectively reduced lung injury and helped maintain the normal structure and function of the respiratory membrane, suggesting it could be a promising therapeutic approach for ARDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor increased the permeability of respiratory barrier in acute respiratory distress syndrome model in mice. Zhang, Z., Wu, Z., Xu, Y., et al.[2022]

In human lung tissue, both VEGFR1 and VEGFR2 showed significant up-regulation in later stages of acute respiratory distress syndrome (ARDS), suggesting their potential role in lung injury recovery.

Neuropilin-1 (NRP-1) was down-regulated in early ARDS but normalized in later stages, indicating a complex temporal regulation of VEGF bioactivity that may contribute to the protective mechanisms in lung injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome. Medford, AR., Ibrahim, NB., Millar, AB.[2023]

Vascular endothelial growth factor (VEGF) is a key player in the development of acute respiratory distress syndrome (ARDS) due to its role in increasing vascular permeability and disrupting the integrity of the alveolar capillary membrane.

Understanding VEGF biology could provide insights into its potential role in both maintaining normal lung function and contributing to lung injury, highlighting its importance in ARDS pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor in acute lung injury and acute respiratory distress syndrome. Barratt, S., Medford, AR., Millar, AB.[2020]

In a randomized trial involving 49 adults with COVID-19-associated ARDS, the drug FX06 did not significantly reduce vascular leakage compared to placebo, as measured by the extravascular lung-water index over 7 days.

While adverse event rates were similar between the FX06 and placebo groups, a higher incidence of ventilator-associated pneumonia was observed in the FX06 group, suggesting potential safety concerns that need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial. Guérin, E., Belin, L., Franchineau, G., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Understanding and managing the possible adverse effects associated with bevacizumab. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A pharmacovigilance study of adverse event profiles and haemorrhagic safety of bevacizumab based on the FAERS database. [2023]

3. Cyprus pubmed.ncbi.nlm.nih.gov

Implication of bevacizumab in fatal arterial thromboembolic incidents. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Intricacies of bevacizumab-induced toxicities and their management. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Emerging safety data for bevacizumab in advanced non-small-cell lung cancer. [2015]

6. England pubmed.ncbi.nlm.nih.gov

VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells. [2020]

7. France pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor increased the permeability of respiratory barrier in acute respiratory distress syndrome model in mice. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor in acute lung injury and acute respiratory distress syndrome. [2020]

10. England pubmed.ncbi.nlm.nih.gov

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial. [2023]