A Phase Ib/II in Patients With Acute Ischemic Stroke

NCT02963376 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 205529
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (2)

• NIHSS Assessment

  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.

• Modified Rankin Scale (mRS)

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

Study Arms (6)

0.05 mL/kg DDFPe

ACTIVE COMPARATOR

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.

Drug: 0.05 mL/kg DDFPe

0.05 mL/kg Placebo

PLACEBO COMPARATOR

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.

Drug: 0.05 mL/kg Placebo

0.10 mL/kg DDFPe

ACTIVE COMPARATOR

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.

Drug: 0.10 mL/kg DDFPe

0.10 mL/kg Placebo

PLACEBO COMPARATOR

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.

Drug: 0.10 mL/kg Placebo

0.17 mL/kg DDFPe

ACTIVE COMPARATOR

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.

Drug: 0.17 mL/kg DDFPe

0.17 mL/kg Placebo

PLACEBO COMPARATOR

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.

Drug: 0.17 mL/kg Placebo

Interventions

0.05 mL/kg DDFPe DRUG

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).

Also known as: Dodecafluoropentane emulsion (DDFPe), NanO2TM

0.05 mL/kg DDFPe

0.05 mL/kg Placebo DRUG

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).

0.05 mL/kg Placebo

0.10 mL/kg DDFPe DRUG

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).

Also known as: Dodecafluoropentane emulsion (DDFPe), NanO2TM

0.10 mL/kg DDFPe

0.10 mL/kg Placebo DRUG

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).

0.10 mL/kg Placebo

0.17 mL/kg DDFPe DRUG

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).

Also known as: Dodecafluoropentane emulsion (DDFPe), NanO2TM

0.17 mL/kg DDFPe

0.17 mL/kg Placebo DRUG

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).

0.17 mL/kg Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NuvOx LLC: lead
• University of Arkansas: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• 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.

  PMID: 31349978 RESULT

Related Links

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

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

Limitations of the current study primarily concern the exploratory aim toward efficacy, which was greatly underpowered for any purpose other than designing the next study. As with any phase I trial, the small number of cases may only demonstrate side effects and complications that are common.

Results Point of Contact

• Title: Evan Unger, MD
• Organization: NuvOx Pharma

eunger@nuvoxpharma.com

520-624-6688

Study Officials

• William Culp, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

• Sanjeeva Onteddu, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 15, 2016
• Study Start: February 1, 2017
• Primary Completion: July 9, 2018
• Study Completion: July 9, 2018
• Last Updated: September 24, 2021
• Results First Posted: September 24, 2021

Record last verified: 2021-08

Locations

US (1)