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NCT06701656PHASE2Recruiting

JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort C: Bevacizumab

PPD Development, LP

Start Date

10/28/2025

Completion Date

9/1/2028

Summary

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.

Detailed Description

This is a master protocol for a Phase 2 platform clinical trial to evaluate host-directed therapeutic candidates (i.e., investigational product, IP) for the treatment of hospitalized participants diagnosed with ARDS. The safety and efficacy of each IP will be studied within its own cohort (IP versus Placebo). All patients will continue to receive standard treatments for ARDS as per the investigator. An individual participant will complete the study in approximately 90 days. The study will include a screening period (\<24 hours from providing informed consent to treatment), in-hospital treatment period with IP/placebo starting on Day 1 through discharge from the hospital, and a follow-up period after discharge from the hospital through the end of study (Day 90 + 2 weeks). Outcome data will be assembled for each patient over time (such as ventilatory status, oxygenation, and survival). Functional status using the WHO Ordinal scale and Karnofsky scale will be collected. Resource utilization will be calculated (length of stay in a critical care setting, days intubated, and survival). All participants will undergo a series of physical exams, laboratory assessments/biomarker collections, ECG, Chest X-ray or CT scan, and questionnaires through Day 90. Exploratory biomarkers will be evaluated over time to facilitate clinical learning. This record only includes information relevant to the bevacizumab cohort.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: The following inclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073. * ARDS Severity of mild, moderate or severe, based on PaO2/FiO2 or SpO2/FiO2 assessment at the time of randomization. Exclusion Criteria: The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073. * Participant has a known allergy or hypersensitivity to the active substance/excipients, or Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies * Participant with established cirrhosis and a modified Child-Pugh Score of 7 or greater * Participant was dialysis-dependent prior to hospitalization. Participant must have a urine dipstick for proteinuria \< 2+ * The hospitalized participant has a history or currently experiencing the following: 1. Participant must not have an international normalized ratio (INR) \>1.5 and/or aPTT \>1.5 × upper limit of normal (ULN) within 7 days prior to initiation of study treatment for participants not receiving anticoagulation. For participants on full dose oral or parenteral anticoagulants for therapeutic purposes the INR and/or activated partial thromboplastin time (aPTT) must be within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the participant on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. 2. Participant with recent serious hemorrhage or history of recent hemoptysis \> 2 episodes (defined as ≥2.5 mL of bright red blood per episode) within 1 month of screening. 3. Participant with inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg). Antihypertensive therapy is permitted to achieve these parameters. 4. Participant with a history of hypertensive crisis or hypertensive encephalopathy. 5. Participant with a history of Grade ≥ 4 venous thromboembolisms. 6. Participant with significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 3 months of study drug treatment. 7. Participant with history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or active gastrointestinal bleeding within 6 months of study drug treatment. 8. Participant with serious, non-healing wound, active ulcer, or untreated bone fracture. 9. Participant with history or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (ie, in the absence of therapeutic anticoagulation). 10. Participant with clinically significant cardiovascular disease including cerebrovascular accident or myocardial infarction within previous 6 months, unstable angina, congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication. 11. Participant with a platelet count of \<75×109/L. 12. Participant with current or recent (\<10 days prior to initiation of study treatment) use of aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day). 13. Participant is receiving a direct anticoagulant (DOAC) such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) without the availability of a reversal agent at the site. 14. Participant is receiving a DOAC such as betrixaban (Bevyxxa®) and edoxaban (Lixiana®) for which there is no approved reversal agent. 15. Participant has urine dipstick for proteinuria ≥ 2+

Interventions

DRUG

Cohort C: bevacizumab

DRUG

Cohort C: placebo

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Conditions

Acute Respiratory Distress Syndrome (ARDS)ARDSARDS (Acute Respiratory Distress Syndrome)Acute Respiratory Distress Syndrome

Locations

University of Alabama Hospital

Birmingham, Alabama 35233-1932

United States

Community Regional Medical Center

Fresno, California 93721-1324

United States

Long Beach Memorial Medical Center

Long Beach, California 90806-1701

United States

University of California Irvine Medical Center

Orange, California 92868-3201

United States

University of California Davis Medical Center - Pulmonary Medicine

Sacramento, California 95816-4300

United States

Stanford Medical Center

Stanford, California 94305-2200

United States

Denver Health Hospital and Authority

Denver, Colorado 80204-4532

United States

MedStar Washington Hospital Center

Washington D.C., District of Columbia 20010-3017

United States

Nova Clinical Research

Bradenton, Florida 34209-4617

United States

North Florida / South Georgia Veterans Health System

Gainesville, Florida 32608-1135

United States

Sarasota Memorial Hospital

Sarasota, Florida 34239

United States

St. Luke's Boise Medical Center

Boise, Idaho 83712-6241

United States

Northshore University Healthsystem Research Institute

Evanston, Illinois 60201-1700

United States

OSF Saint Francis Medical Center-

Peoria, Illinois 61637-0001

United States

Tufts Medical Center

Boston, Massachusetts 02111

United States

Lahey Hospital and Medical Center

Burlington, Massachusetts 01805-0001

United States

University of Michigan Hospital

Ann Arbor, Michigan 48109-5000

United States

Henry Ford Health Hospital

Detroit, Michigan 48202-2608

United States

Mayo Clinic

Rochester, Minnesota 55905-0001

United States

Renown Institute for Heart & Vascular Health

Reno, Nevada 89502-1576

United States

Robert Wood Johnson Medical School

New Brunswick, New Jersey 08901-1928

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065-6007

United States

Weill Cornell Medical College

New York, New York 10065-8722

United States

Montefiore Hospital - Moses Campus

The Bronx, New York 10467

United States

Westchester Medical Center

Valhalla, New York 10595-1530

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599-0001

United States

Durham VA Medical Center

Durham, North Carolina 27705-3875

United States

Duke Lung Transplant Clinic - Clinic 2F/2G - PPDS

Durham, North Carolina 27710-4000

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106-1716

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Mercy Health - St. Vincent Medical Center

Toledo, Ohio 43608-2603

United States

The University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104-3609

United States

Oregon Health and Science University

Portland, Oregon 97239-3011

United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina 29425-8908

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232-0004

United States

Baylor All Saints Medical Center

Fort Worth, Texas 76104-4110

United States

Baylor St Luke's Medical Center

Houston, Texas 77030-4202

United States

Houston Methodist Hospital

Houston, Texas 77030

United States

Intermountain Medical Center

Murray, Utah 84107-5701

United States

University of Virginia Health System

Charlottesville, Virginia 22908-0816

United States

Swedish Medical Center

Seattle, Washington 98122-4379

United States