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

Purpose

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.

Conditions

  • Acute Respiratory Distress Syndrome (ARDS)
  • ARDS
  • ARDS (Acute Respiratory Distress Syndrome)
  • Acute Respiratory Distress Syndrome

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
The overall 2-step randomization scheme will be implemented. - Randomization Level 1 will be open-label, assigning an eligible patient to one of the available treatment cohorts. - Randomization Level 2 will be double-blinded and will randomize participants at a 1:1 ratio to receive either IP or placebo within a specific cohort. Thus, the PPD blinded team, site blinded staff members, and participants/legal authorized representative will be considered blinded to study treatment assignment (either IP or placebo) throughout the course of the study. To preserve the integrity of the study blind, an unblinded pharmacist at each site will be responsible for the reconstitution and dispensation of all study drugs and placebos and will endeavor to ensure that there are no observable differences between the treatment groups (IP or placebo) when dispensing the study materials.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort C: bevacizumab
  • Drug: Cohort C: bevacizumab
    Administered as a single IV dose of 500 mg on Day 1
Placebo Comparator
Cohort C: placebo
  • Drug: Cohort C: placebo
    Administered as a single IV dose of placebo on Day 1

Recruiting Locations

Community Regional Medical Center
Fresno 5350937, California 5332921 93721-1324

Long Beach Memorial Medical Center
Long Beach 5367929, California 5332921 90806-1701

University of California Irvine Medical Center
Orange 5379513, California 5332921 92868-3201

University of California Davis Medical Center - Pulmonary Medicine
Sacramento 5389489, California 5332921 95816-4300

Denver Health Hospital and Authority
Denver 5419384, Colorado 5417618 80204-4532

MedStar Washington Hospital Center
Washington D.C. 4140963, District of Columbia 4138106 20010-3017

Nova Clinical Research
Bradenton 4148708, Florida 4155751 34209-4617

North Florida / South Georgia Veterans Health System
Gainesville 4156404, Florida 4155751 32608-1135

Sarasota Memorial Hospital
Sarasota 4172131, Florida 4155751 34239

St. Luke's Boise Medical Center
Boise 5586437, Idaho 5596512 83712-6241

OSF Saint Francis Medical Center-
Peoria 4905687, Illinois 4896861 61637-0001

Lahey Hospital and Medical Center
Burlington 4931737, Massachusetts 6254926 01805-0001

University of Michigan Hospital
Ann Arbor 4984247, Michigan 5001836 48109-5000

Henry Ford Health Hospital
Detroit 4990729, Michigan 5001836 48202-2608

Mayo Clinic
Rochester 5043473, Minnesota 5037779 55905-0001

Robert Wood Johnson Medical School
New Brunswick 5101717, New Jersey 5101760 08901-1928

Montefiore Hospital - Moses Campus
The Bronx 5110266, New York 5128638 10467

University of North Carolina at Chapel Hill
Chapel Hill 4460162, North Carolina 4482348 27599-0001

Durham VA Medical Center
Durham 4464368, North Carolina 4482348 27705-3875

Mercy Health - St. Vincent Medical Center
Toledo 5174035, Ohio 5165418 43608-2603

The University of Oklahoma Health Sciences Center
Oklahoma City 4544349, Oklahoma 4544379 73104-3609

Oregon Health and Science University
Portland 5746545, Oregon 5744337 97239-3011

Medical University of South Carolina (MUSC)
Charleston 4574324, South Carolina 4597040 29425-8908

Vanderbilt University Medical Center
Nashville 4644585, Tennessee 4662168 37232-0004

Baylor All Saints Medical Center
Fort Worth 4691930, Texas 4736286 76104-4110

Intermountain Medical Center
Murray 5778755, Utah 5549030 84107-5701

Swedish Medical Center
Seattle 5809844, Washington 5815135 98122-4379

More Details

NCT ID
NCT06701656
Status
Recruiting
Sponsor
PPD Development, LP

Study Contact

Just Breathe Trial Team
Please email
crgjustbreathealerts.sm@thermofisher.com

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.