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A Phase Ib/II in Patients With Acute Ischemic Stroke

Primary Purpose

Ischemic Stroke

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

0.05 mL/kg DDFPe

0.05 mL/kg Placebo

0.10 mL/kg DDFPe

0.10 mL/kg Placebo

0.17 mL/kg DDFPe

0.17 mL/kg Placebo

About this trial

This is an interventional treatment trial for Ischemic Stroke

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ages 18-80 years
Diagnosis of AIS
Body weight ≥ 45 kg
NIHSS between 2 and 20
Patient or legal authorized representative (LAR) must be willing and able to understand the study and provide written informed consent

Exclusion Criteria:

Currently pregnant or breastfeeding

History of significantly impaired renal or hepatic function
Hemorrhage or hemorrhagic stroke on CT scan
Prior stroke, intracranial surgery, or major head trauma within three months prior to enrollment
Pre-stroke modified Rankin Scale (mRS) ≥ 2
Myocardial infarction within six (6) months prior to enrollment
Unstable angina, New York Heart Association (NYHA) Class II or greater congestive heart failure
Uncontrolled hypertension (SBP > 180 and/or diastolic blood pressure (DBP) > 110 mmHg)
Known long QT syndrome or QTc > 450 milliseconds (ms) in males and > 470 ms in females
Uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six (6) months (except atrial fibrillation)
Clinically significant chronic obstructive pulmonary disease (COPD) or other pulmonary condition that is not controlled by medication or requires oxygen frequently or continuously
Pneumonia, bronchitis, or other acute respiratory disease
Current anticoagulant therapy except for antiplatelet therapy (aspirin, NSAIDs) and prophylactic doses of low molecular weight heparin to prevent deep vein thrombosis. Note: tPA administered as part of subjects' therapy for AIS is allowed.
History of allergic reaction attributed to compounds of similar chemical composition to DDFPe (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

Sites / Locations

University of Arkansas for Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

0.05 mL/kg DDFPe

0.05 mL/kg Placebo

0.10 mL/kg DDFPe

0.10 mL/kg Placebo

0.17 mL/kg DDFPe

0.17 mL/kg Placebo

Arm Description

This study is a randomized, placebo controlled, blinded escalating dose study designed to determine the maximum tolerated dose to intravenous administration of DDFPe. At each of the three dose levels 0.10, 0.17 mL/kg) six subjects will receive DDFPe and two will receive placebo.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of DDFPe Evaluated by Number of Dose Limiting Toxicities

The primary objective of this study is to establish the Maximum Tolerated Dose (MTD) of DDFPe given intravenously at intervals of 90 ± 10 minutes x 3 doses within 12 hours after subjects have had a documented Acute Ischemic Stroke (AIS). The algorithm for determining the MTD is based on the number of subjects who experience a Dose Limiting Toxicity (DLT) in each cohort, as defined in the clinical protocol. If three or more subjects who received DDFPe in an 8 subject cohort experience a DLT, the MTD will be determined to have been exceeded and further enrollment in the cohort as well as dose escalation will stop.

Secondary Outcome Measures

NIHSS Assessment

The NIH Stroke Scale (NIHSS) is an assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The NIHSS is a 15-item neurologic examination. Ratings for each item are scored on a 3- to 5-point scale with 0 as normal. Scores range from 0 to 42, with higher scores indicating greater severity.

Modified Rankin Scale (mRS)

The modified Rankin Scale is a measure of the degree of disability in patients who have had a stroke with 0 being no symptoms at all to 6 being death. Thus, a higher score indicates greater severity.

Full Information

NCT ID

NCT02963376

First Posted

November 10, 2016

Last Updated

August 30, 2021

Sponsor

NuvOx LLC

Collaborators

University of Arkansas

1. Study Identification

Unique Protocol Identification Number

NCT02963376

Brief Title

A Phase Ib/II in Patients With Acute Ischemic Stroke

Official Title

A Phase Ib/II Dose-finding Study of DDFPe in Patients With Acute Ischemic Stroke

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

February 1, 2017 (Actual)

Primary Completion Date

July 9, 2018 (Actual)

Study Completion Date

July 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NuvOx LLC

Collaborators

University of Arkansas

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Stroke is the fifth leading cause of death in the United States and is the leading cause of long term disability. Distinct geographic disparities in stroke mortality, with highest rates in the southeast United States including Arkansas, are known as the "stroke belt." There the average stroke mortality is ≈20% to 40% higher than the rest of the nation. Stroke is the leading cause of serious long-term disability. Between 2012 and 2030, disability and medical costs related to stroke are projected to triple, from $71.6 billion to $184.1 billion, with the majority of the projected increase in costs arising from those 65 to 79 years of age. There are two main forms of stroke, ischemic and hemorrhagic. An ischemic stroke occurs in 85% of cases and is caused by cerebral vessel occlusion, obstructing blood flow to a portion of the brain. Currently, the only approved therapies for acute ischemic stroke are IV tissue plasminogen activator (tPA), a thrombolytic agent that clears the thrombus within the blood vessel, or intra-arterial catheter thrombectomy. Despite the availability of therapy, it reaches only approximately 7% of ischemic stroke victims in the United States5. Delay beyond the effective time window for therapy is a common reason for failure. To reduce the devastating impact of stroke on individuals and society, the investigators continue to seek ways to improve functional recovery and limit ischemic damage in stroke patients. The potential neuroprotective agent, dodecafluoropentane emulsion (DDFPe) has recently shown strong positive effects in pre-clinical animal models of acute ischemic stroke6-11. Other perfluorocarbons have been tested in humans as potential neuroprotectants and blood substitutes yet none have been successful.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

0.05 mL/kg DDFPe

Arm Type

Active Comparator

Arm Description

Arm Title

0.05 mL/kg Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

0.10 mL/kg DDFPe

Arm Type

Active Comparator

Arm Description

Arm Title

0.10 mL/kg Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

0.17 mL/kg DDFPe

Arm Type

Active Comparator

Arm Description

Arm Title

0.17 mL/kg Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

0.05 mL/kg DDFPe

Other Intervention Name(s)

Dodecafluoropentane emulsion (DDFPe), NanO2TM

Intervention Description

Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.05 mL/kg based on patient body weight in kilograms (kg).

Intervention Type

Drug

Intervention Name(s)

0.05 mL/kg Placebo

Intervention Description

Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.05 mL/kg is based on patient body weight in kilograms (kg).

Intervention Type

Drug

Intervention Name(s)

0.10 mL/kg DDFPe

Other Intervention Name(s)

Dodecafluoropentane emulsion (DDFPe), NanO2TM

Intervention Description

Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.10 mL/kg based on patient body weight in kilograms (kg).

Intervention Type

Drug

Intervention Name(s)

0.10 mL/kg Placebo

Intervention Description

Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.10 mL/kg is based on patient body weight in kilograms (kg).

Intervention Type

Drug

Intervention Name(s)

0.17 mL/kg DDFPe

Other Intervention Name(s)

Dodecafluoropentane emulsion (DDFPe), NanO2TM

Intervention Description

Prior to injection, DDFPe will be prepared by pharmacy staff. DDFPe will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. DDFPe dosage volume in cc for 0.17 mL/kg based on patient body weight in kilograms (kg).

Intervention Type

Drug

Intervention Name(s)

0.17 mL/kg Placebo

Intervention Description

Prior to injection, the placebo will be prepared by pharmacy staff. The placebo will be administered based on weight at designated doses. Each dose will be prepared on the day of administration and infused directly into the patient using a slow i.v push. The i.v. push shall be 5-10 minutes in duration. The placebo dosage volume in cc for 0.17 mL/kg is based on patient body weight in kilograms (kg).

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) of DDFPe Evaluated by Number of Dose Limiting Toxicities

Description

Time Frame

12 hours after subjects have had a documented Acute Ischemic Stroke (AIS)

Secondary Outcome Measure Information:

Title

NIHSS Assessment

Description

Time Frame

NIHSS scores were recorded at outside hospitals when appropriate and also at the study center as inside baseline NIHSS score. Repeat NIHSS scores were recorded at 2, 3.5, and 7.5 hours after drug injection and on discharge.

Title

Modified Rankin Scale (mRS)

Description

The modified Rankin Scale is a measure of the degree of disability in patients who have had a stroke with 0 being no symptoms at all to 6 being death. Thus, a higher score indicates greater severity.

Time Frame

mRS values were obtained on Day 7 or Day of Discharge, Day 30 and Day 90.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ages 18-80 years Diagnosis of AIS Body weight ≥ 45 kg NIHSS between 2 and 20 Patient or legal authorized representative (LAR) must be willing and able to understand the study and provide written informed consent Exclusion Criteria: Currently pregnant or breastfeeding History of significantly impaired renal or hepatic function Hemorrhage or hemorrhagic stroke on CT scan Prior stroke, intracranial surgery, or major head trauma within three months prior to enrollment Pre-stroke modified Rankin Scale (mRS) ≥ 2 Myocardial infarction within six (6) months prior to enrollment Unstable angina, New York Heart Association (NYHA) Class II or greater congestive heart failure Uncontrolled hypertension (SBP > 180 and/or diastolic blood pressure (DBP) > 110 mmHg) Known long QT syndrome or QTc > 450 milliseconds (ms) in males and > 470 ms in females Uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six (6) months (except atrial fibrillation) Clinically significant chronic obstructive pulmonary disease (COPD) or other pulmonary condition that is not controlled by medication or requires oxygen frequently or continuously Pneumonia, bronchitis, or other acute respiratory disease Current anticoagulant therapy except for antiplatelet therapy (aspirin, NSAIDs) and prophylactic doses of low molecular weight heparin to prevent deep vein thrombosis. Note: tPA administered as part of subjects' therapy for AIS is allowed. History of allergic reaction attributed to compounds of similar chemical composition to DDFPe (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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William Culp, MD

Organizational Affiliation

University of Arkansas

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Sanjeeva Onteddu, MD

Organizational Affiliation

University of Arkansas

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Arkansas for Medical Sciences

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31349978

Citation

Culp WC, Onteddu SS, Brown A, Nalleballe K, Sharma R, Skinner RD, Witt T, Roberson PK, Marsh JD. Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial. J Vasc Interv Radiol. 2019 Aug;30(8):1244-1250.e1. doi: 10.1016/j.jvir.2019.04.020.

Results Reference

result

Links:

URL

https://pubmed.ncbi.nlm.nih.gov/31349978/

Description

Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial

Learn more about this trial

A Phase Ib/II in Patients With Acute Ischemic Stroke

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