Innovative Therapies 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: Immunosuppressants, Chemotherapy

Disqualifiers: Pregnancy, Severe COPD, Active cancer, 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: 91

Duration: Varies (until hospital discharge)

600 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive therapy or have recently taken investigational drugs, you may not be eligible. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Bevacizumab for treating Acute Respiratory Distress Syndrome?

Bevacizumab has been shown to be effective in treating various cancers by targeting VEGF, a protein that helps tumors grow by forming new blood vessels. This mechanism might also help in conditions like Acute Respiratory Distress Syndrome, where controlling blood vessel growth and inflammation could be beneficial. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Bevacizumab, used in cancer treatment, has been linked to serious side effects like stroke, heart attack, and bleeding in the lungs. It also carries a risk of gastrointestinal perforation, which is a serious condition where a hole forms in the stomach or intestines. ^{6 7 8 9 10}

How is the drug Bevacizumab unique in treating Acute Respiratory Distress Syndrome?

Bevacizumab is unique because it targets vascular endothelial growth factor (VEGF), which is involved in the formation of new blood vessels, and this mechanism is different from traditional treatments for conditions like lung cancer. This approach may offer a novel way to manage Acute Respiratory Distress Syndrome by potentially reducing inflammation and fluid buildup in the lungs. ^{11 12 13 14 15}

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. Participants will be randomized to receive either a placebo or one of the active treatments. This record describes the default procedures and analyses for all cohorts. Each specific cohort may have additional eligibility requirements, safety and efficacy procedures, or endpoints, which will be described in the corresponding intervention-specific records on clinicaltrials.gov listed below in the detailed description.

Eligibility Criteria

Adults diagnosed with ARDS who can consent and follow the study rules. They must fit the Berlin definition of ARDS, may be on noninvasive ventilation, and agree not to join other studies until Day 90. Participants of childbearing potential must use certain contraception methods.

Inclusion Criteria

Participant (or their Legally Authorized Representative (LAR)) provides informed consent and agrees to comply with protocol requirements

Participant of childbearing potential must agree to either abstinence or use at least one primary form of contraception, not including hormonal contraception, from the time of screening through Day 28. Additional cohort-specific requirements may apply

Participant agrees to not participate in another investigational interventional study while participating in this study (i.e., through Day 90)

Exclusion Criteria

Participant has a known allergy to any study medication or any of its excipients

Participant is known to be pregnant, nursing, or with a positive (urine and/or serum test) pregnancy test

Participant is anticipated to be transferred to another hospital which is not a study site within 72 hours

Timeline

Screening

Participants are screened for eligibility to participate in the trial

<24 hours

1 visit (in-person)

Treatment

Participants receive investigational product or placebo from Day 1 through discharge from the hospital

Varies (until hospital discharge)

Daily monitoring (in-hospital)

Follow-up

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

Approximately 12 weeks

Regular assessments through Day 90

Treatment Details

Interventions

• Bevacizumab
• Paridiprubart
• Vilobelimab

Trial Overview This Phase 2 trial tests if vilobelimab, paridiprubart, or bevacizumab can safely treat ARDS compared to a placebo. Patients are randomly assigned to either an active treatment or placebo in a double-blinded manner so neither they nor the researchers know which one they're getting.

Participant Groups

Group I: Cohort C: bevacizumab Experimental Treatment 1 Intervention

Group II: Cohort B: paridiprubart Experimental Treatment 1 Intervention

Group III: Cohort A: vilobelimab Experimental Treatment 1 Intervention

Group IV: Cohort A: placebo Placebo Group 1 Intervention

Group V: Cohort C: placebo Placebo Group 1 Intervention

Group VI: Cohort B: 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

Edesa Biotech Inc.

Industry Sponsor

Trials

6

Recruited

2,100+

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

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)

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Findings from Research

Ramucirumab, a fully humanized monoclonal antibody targeting the vascular endothelial growth factor receptor-2, shows promise as a novel antiangiogenic treatment for various cancers, including gastrointestinal, breast, lung, and genitourinary tumors.

The REGARD trial was the first phase III study to demonstrate the efficacy of ramucirumab as a single agent in advanced cancer, with ongoing trials further exploring its effectiveness both alone and in combination with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. Aprile, G., Bonotto, M., Ongaro, E., et al.[2023]

In a phase 3 trial involving 1343 patients with high-risk melanoma, bevacizumab did not significantly improve overall survival compared to observation, with a hazard ratio of 0.97, indicating similar mortality rates between the two groups.

However, patients receiving bevacizumab experienced a better disease-free interval, suggesting it may help delay recurrence, although it also led to a higher incidence of serious side effects, particularly grade 3 hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study. Corrie, PG., Marshall, A., Dunn, JA., et al.[2022]

The combination of bevacizumab and atezolizumab in patients with metastatic non-small cell lung cancer (NSCLC) showed a significant increase in disease control rate (DCR) from 35.7% after atezolizumab alone to 87.5% after adding bevacizumab, indicating enhanced treatment efficacy.

The treatment was well-tolerated, with only 25% of patients experiencing treatment-related adverse events, all of which were mild (grade 1 or 2), suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab Plus Atezolizumab After Progression on Atezolizumab Monotherapy in Pretreated Patients With NSCLC: An Open-Label, Two-Stage, Phase 2 Trial. Lee, J., Koh, J., Kim, HK., et al.[2022]

Bevacizumab, an anti-VEGF monoclonal antibody, has been shown to significantly improve survival in patients with metastatic colorectal cancer when used in combination with chemotherapy, based on large Phase III clinical trials.

The treatment is generally well tolerated, although it can cause side effects such as hypertension and arterial thromboembolic events, and its effectiveness in the adjuvant setting is currently being studied in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in the treatment of metastatic colorectal cancer. Caprioni, F., Fornarini, G.[2015]

Ramucirumab is a fully human monoclonal antibody that specifically inhibits VEGF receptor-2, which plays a key role in cancer-related blood vessel changes, making it a promising candidate for treating solid tumors.

Phase I clinical trials have demonstrated that ramucirumab is safe across various doses and has shown early signs of effectiveness, including stable disease and partial responses in multiple tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab (IMC-1121B): a novel attack on angiogenesis. Spratlin, JL., Mulder, KE., Mackey, JR.[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]

Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) are at an increased risk of severe pulmonary hemorrhage (PH) when treated with bevacizumab, especially if they have squamous histology or a history of significant hemoptysis, indicating these patients should not receive this treatment.

While certain factors like major blood vessel infiltration may suggest a higher risk of PH, there are no reliable clinical or radiological predictors for severe PH in patients treated with bevacizumab, highlighting the need for careful individual risk assessments before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting and managing the risk of pulmonary haemorrhage in patients with NSCLC treated with bevacizumab: a consensus report from a panel of experts. Reck, M., Barlesi, F., Crinò, L., et al.[2023]

Aflibercept, used in cancer treatment, was found to increase the risk of fatal adverse events (FAEs) in patients, with an overall incidence of 5.1% among 3,060 patients analyzed from ten clinical trials.

The most common causes of FAEs linked to aflibercept were infections (38.8%), hemorrhage (5.9%), and gastrointestinal perforation (5.9%), indicating that while aflibercept is effective, careful monitoring for these serious side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related mortality with aflibercept in cancer patients: a meta-analysis. Qi, WX., Tang, LN., Shen, Z., et al.[2021]

In a study of 48 patients with advanced non-squamous non-small cell lung cancer and pre-existing interstitial lung disease, the addition of bevacizumab (Bev) to chemotherapy significantly reduced the incidence of acute exacerbation of interstitial lung disease (AE-ILD) to 0%, compared to 22.6% in those not receiving Bev.

Patients receiving Bev also experienced a longer median progression-free survival of 8.0 months compared to 4.3 months in the non-Bev group, suggesting that Bev not only helps reduce AE-ILD risk but may also improve overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effect of bevacizumab on chemotherapy-related acute exacerbation of interstitial lung disease in patients with advanced non-squamous non-small cell lung cancer. Hamada, S., Ichiyasu, H., Ikeda, T., et al.[2020]

In a systematic review of 12,294 patients across 17 trials, bevacizumab was found to significantly increase the risk of gastrointestinal perforation, with an incidence rate of 0.9% and a relative risk of 2.14 compared to control treatments.

The risk of gastrointestinal perforation varied based on the dose of bevacizumab and the type of cancer, with the highest risks observed in patients with colorectal carcinoma (relative risk 3.10) and renal cell cancer (relative risk 5.67).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Hapani, S., Chu, D., Wu, S.[2022]

Bevacizumab is the first approved drug targeting vascular endothelial growth factor (VEGF) for metastatic colorectal cancer and is being tested in phase III trials for other cancers, including earlier-stage diseases.

Research is exploring ways to enhance the effectiveness of bevacizumab, such as combining it with other targeted therapies and optimizing dosing schedules, while also investigating its mechanisms of action through noninvasive imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions in vascular endothelial growth factor-targeted therapy for metastatic colorectal cancer. Grothey, A.[2015]

Ramucirumab, a monoclonal antibody targeting VEGFR2, has demonstrated effectiveness as a second-line treatment for patients with advanced gastric and colorectal cancers, based on evidence from trials like REGARD and RAINBOW.

The ongoing studies are exploring the use of ramucirumab in various gastrointestinal cancers, indicating its potential to change treatment approaches in these malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab for the treatment of gastric cancers, colorectal adenocarcinomas, and other gastrointestinal malignancies. Aprile, G., Ferrari, L., Cremolini, C., et al.[2023]

Intravitreal injection of ranibizumab in 38 eyes of 19 premature infants with aggressive posterior retinopathy of prematurity (AP-ROP) resulted in significant regression of retinopathy and allowed for continued development of retinal vessels, with 24 eyes showing complete regression.

No infections or complications were reported in any of the infants, indicating that ranibizumab is a safe and effective treatment for AP-ROP, although some cases may require additional laser photocoagulation for complete resolution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical study on intravitreous injection of ranibizumab for aggressive posterior retinopathy of prematurity]. Tian, R., Zhang, G., Tang, S., et al.[2018]

In a Phase I trial involving 11 patients with rectal cancer, the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy was found to be tolerable, with an acceptable toxicity profile at the recommended Phase II dose.

The treatment showed promising efficacy, with 6 patients demonstrating clinical responses, including 2 achieving a pathologic complete response, indicating potential effectiveness for further investigation in a Phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results. Czito, BG., Bendell, JC., Willett, CG., et al.[2018]

Adding bevacizumab to standard chemotherapy (carboplatin plus paclitaxel) for advanced nonsmall cell lung cancer (NSCLC) significantly improves response rates and prolongs time to disease progression, resulting in an overall survival extension of about 2.3 months.

While bevacizumab shows promise in enhancing treatment outcomes, it is associated with risks such as episodes of bleeding, particularly pulmonary hemorrhage, and its high cost may impact its cost-effectiveness despite limited treatment options for patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab: the evidence for its clinical potential in the treatment of nonsmall cell lung cancer. Haslam, S., Chrisp, P.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. [2023]

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

Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study. [2022]

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

Bevacizumab Plus Atezolizumab After Progression on Atezolizumab Monotherapy in Pretreated Patients With NSCLC: An Open-Label, Two-Stage, Phase 2 Trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in the treatment of metastatic colorectal cancer. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Ramucirumab (IMC-1121B): a novel attack on angiogenesis. [2023]

6. Cyprus pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Predicting and managing the risk of pulmonary haemorrhage in patients with NSCLC treated with bevacizumab: a consensus report from a panel of experts. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Treatment-related mortality with aflibercept in cancer patients: a meta-analysis. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Protective effect of bevacizumab on chemotherapy-related acute exacerbation of interstitial lung disease in patients with advanced non-squamous non-small cell lung cancer. [2020]

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

Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. [2022]

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

Future directions in vascular endothelial growth factor-targeted therapy for metastatic colorectal cancer. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Ramucirumab for the treatment of gastric cancers, colorectal adenocarcinomas, and other gastrointestinal malignancies. [2023]

13. China pubmed.ncbi.nlm.nih.gov

[The clinical study on intravitreous injection of ranibizumab for aggressive posterior retinopathy of prematurity]. [2018]

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

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results. [2018]

15. New Zealand pubmed.ncbi.nlm.nih.gov

Bevacizumab: the evidence for its clinical potential in the treatment of nonsmall cell lung cancer. [2021]