NanO2 for Large Vessel Occlusion Stroke

Ischemic Stroke Clinical Trial

— PROVEN  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05389748
• Other study ID #: PROVEN-P2
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: April 1, 2023
• Est. completion date: September 1, 2025

Study information

• Verified date: May 2022
• Source: NuvOx LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: September 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

Other:
• Placebo
Subjects with large vessel occlusion stroke eligible for mechanical thrombectomy are randomized to placebo in association with standard of care

Biological:
• dodecafluoropentane emulsion (DDFPe)
Subjects with large vessel occlusion stroke eligible for mechanical thrombectomy are randomized to DDFPe in association with standard of care

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
NuvOx LLC	Stanford University, University of Arkansas, Washington Regional Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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