NanO2 for Large Vessel Occlusion Stroke (PROVEN)

Phase IIb to Restore Oxygen in Large Vessel Occlusion Patients En Route for MT Using NanO2

A two stage phase 2 study with an interim analysis to provide evidence that subjects provided with early administration of NanO2 who are located at small rural spoke hospitals and identified with large vessel occlusion ischemic strokes as well as viable penumbra prior to transfer to larger hub hospitals and who continue dosing NanO2 until revascularization is achieved by intravenous alteplase and/or mechanical thrombectomy, will experience stroke recovery by shifting ischemic brain tissue to normal tissue pO2 environments.

Study Overview

• Status: Not yet recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Other: Placebo; Biological: dodecafluoropentane emulsion (DDFPe)

Detailed Description

Recent stroke studies have shown that subjects with Large Vessel Occlusion (LVO) ischemic stroke have rapid infarct growth. The investigators hypothesize that early administration of NanO2 in subjects with LVO ischemic stroke will maintain the viability of tissue in the penumbra until revascularization is achieved with intravenous alteplase and/or mechanical thrombectomy (MT).

The rationale for administering the dose evaluated is:

1. The dose level is within the levels already tested in animals and humans.5-13 Volunteers received two IV bolus doses of 0.35 mL/kg of activated NanO2TM 24 hours apart and brain cancer subjects received daily doses of up to 0.17 mL/kg of inactivated NanO2TM.18
2. A completed trial of NanO2TM in acute ischemic stroke at the University of Arkansas had the high dose cohort receive three doses of NanO2 (0.17 mL/kg) 90 minutes apart and demonstrated safety at this dose.
3. Therapeutic reduction in stroke damage has been observed at dose levels of 0.1 mL/kg in rabbits.5-9,12 Since drug effects tend to correlate with body surface area/weight, one would predict that a dose of approximately 0.03 mL/kg should be effective in humans compared to rabbits.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18 to 90 years old, male or female
• Diagnosis of LVO ischemic stroke
• Pre-stroke mRS ≤ 2
• NIHSS ≥ 6
• Eligible for mechanical thrombectomy per local criteria
• Subject or LAR must be willing and able to understand the study and provide written informed consent
• Women of childbearing potential or men with child-bearing potential partners (unless vasectomized) must agree to use a highly effective method of birth control from study entry until 4 months after completing study therapy. Should a study participant or their partner become pregnant or suspect a pregnancy they should inform the treating study physician immediately

Exclusion Criteria:

• > 12 hours since onset of stroke symptoms
• Currently pregnant or breastfeeding
• History of significantly impaired renal or hepatic function
• Severe hemorrhage or severe hemorrhagic stroke on CT scan. Mild or moderate changes of Fisher Grade 1 or 2 subarachnoid hemorrhage are allowed as are hemorrhagic transformation changes of Grade HI-1 and HI-224,25
• Unable to undergo a contrast brain perfusion scan with either MRI or CT
• Pre-stroke mRS > 2 (See Appendix 3)
• Unstable angina, NYHA Class II or greater congestive heart failure
• Uncontrolled hypertension (Systolic BP ≥ 200 and/or Diastolic BP ≤ 120 mmHg)
• Uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six (6) months (except atrial fibrillation)
• Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
• History of allergic reaction attributed to compounds of similar chemical composition to NanO2TM (see Investigator's Brochure).
• Subject has received any investigational drug within thirty (30) days prior to enrollment into the study
• Inability to comply with the study procedures
• History or evidence of any other clinically significant condition that, in the opinion of the investigator, might pose a safety risk to subjects or interfere with study procedures, evaluation, or completion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo which appears the same as the treatment to investigators, clinicians and subjects.	Other: Placebo; Subjects with large vessel occlusion stroke eligible for mechanical thrombectomy are randomized to placebo in association with standard of care
ACTIVE_COMPARATOR: NanO2; A milky white intravenous injectable emulsion	Biological: dodecafluoropentane emulsion (DDFPe); Subjects with large vessel occlusion stroke eligible for mechanical thrombectomy are randomized to DDFPe in association with standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National Institutes of Health Stroke Scale and Modified Rankin Scale	Both are established and accepted measures of stroke. NIHSS has a scale from 0 to 42 and mRS has a scale from 0 to 6. In both cases, a lower score represents less brain damage.	2 years

Collaborators and Investigators

• Sponsor: NuvOx LLC
• Collaborators: Stanford University; University of Arkansas; Washington Regional Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2023
• Primary Completion (ANTICIPATED): April 1, 2025
• Study Completion (ANTICIPATED): September 1, 2025

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (ACTUAL): May 25, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: mechanical thrombectomy; perfusion; penumbra; large vessel occlusion stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: PROVEN-P2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No