Voxelotor for Improving Oxygen Saturation in Adults (Voxelotor)

A Phase 2b Open-Label, Single Arm Study to Evaluate the Efficacy of Voxelotor for Improving Oxygen Saturation and Reducing Ventilatory Support Requirements in Adult Patients With New or Increased Oxygen Requirement

The purpose of the study is to evaluate the efficacy of voxelotor for increasing oxygen saturation in 20 patients with hypoxemia. Specifically, the SpO2/FiO2 ratio will be compared before and after voxelotor use at rest and during exercise (ambulatory patients only).

The primary study objective is to evaluate the efficacy of voxelotor for increasing oxygen saturation in patients with hypoxic hypoxemia as a result of end-stage lung disease or acute lung injury.

The secondary objective is to evaluate the efficacy of voxelotor on allowing de-escalation of supplemental oxygen support.

Study Overview

• Status: Terminated
• Conditions: Acute Lung Injury; End Stage Lung Disease
• Intervention / Treatment: Drug: Voxelotor

Detailed Description

Purpose of the study: Primary study objective is to evaluate the efficacy of voxelotor for increasing oxygen saturation in patients with hypoxic hypoxemia as a result of end-stage lung disease or acute lung injury.

Design and Procedures: The day after obtaining written informed consent, 20 patients will receive 500 mg of voxelotor two times a day (for a total daily dose of 1000 mg per day) for 5 days This dose may increase to a total maximum daily dose of 1500 mg (500 mg three times a day) if subject tolerates initial dose as determined by Principal Investigator (PI).

Physiological data at screening, baseline, study day 1 - 5, and up to two days post voxelotor administration will be recorded from standard of care with the only exception being SpO2/FiO2 (S/F) ratio measurements, which will be obtained at the same intervals but by the qualified and delegated study staff or medical team through the use of an FiO2 weaning maneuver.

Study subjects will be asked to rate their dyspnea symptoms daily to record their perceived shortness of breath.

Blood samples will be collected the day prior to voxelotor administration, on study days 1 - 5, and on the 2 wash-out days following voxelotor administration.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Oxygen dependency due to an end-staged lung disease (pre-lung transplant population) or ALI/acute lung injury (for example but not limited to primary allograft dysfunction, infectious pneumonia, aspiration, non-cardiogenic pulmonary edema). ALI will be defined as per Berlin criteria with a P/F ratio <100 denoting severe ARDS, <200 denoting moderate and <300 mild ARDS. ALI and mild ARDS are considered synonymous. In the event of inability to obtain arterial blood gas analysis to calculate a P/F ratio, we will consider a range of patients requiring standard nasal cannulae flowing at 6l/min to maintain SaO2 >90% as ALI, and Salter High -Flow nasal cannulae at 12-15l/min in order to maintain SaO2>85% as severe ARDS.
• At least 48 hours of stable, increased oxygen requirement or ventilatory support prior to the start of drug administration if consented.

Exclusion Criteria:

• Minors (<18 years)
• Pre-existing congestive cardiac failure (NYHA III or IV)
• Medically significant, non-revascularized coronary artery disease
• Inability to obtain informed consent from LAR
• Pregnancy
• Incarcerated individual.
• Failure of another vital organ.
• Severe hepatic impairment (Childs-Pugh C) or liver enzymes > 4x upper limit of normal (ULN) at screening.
• Unstable acute kidney injury/rising creatinine.
• Chronic neuromuscular disease requiring mechanical ventilation
• Not anticipated to survive >48 hours
• Limited therapeutic goals (do not resuscitate, etc.)
• History of Pulmonary Embolism (PE)
• Requires treatment with Fluconazole or other moderate and strong CYP3A4 inhibitors listed in section 5.6
• A patient with active bleeding complications requiring more than 1 unit of blood transfusion per day, as the PK and PD of Voxelotor in the setting of blood loss and blood transfusion is unknown.
• Participated in another clinical trial of an investigational drug (or medical device) within 30 days or 5-half-lives, whichever is longer, prior to consent, or is currently participating in another trial of an investigational or marketed drug (or medical device)
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
• Any condition or concomitant medication that confounds the ability to interpret data from the study or safely use Voxelotor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Voxelotor Arm; 500 mg of Voxelotor two times a day (for a total daily dose of 1000 mg per day) for 5 days. This dose may increase to a total maximum daily dose of 1500 mg (500 mg three times a day), if subject tolerates the initial dose as determined by study doctor.	Drug: Voxelotor; 500 mg of voxelotor will be administered two times a day (for a total daily dose of 1000 mg per day) for 5 days. This dose may increase to a total maximum daily dose of 1500 mg (500 mg three times a day) if subject tolerates initial dose as determined by Principal Investigator (PI).; Other Names: Oxbryta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SpO2/FiO2 (S/F) Ratio From Baseline to 2 Days After Initiation of Voxelotor Treatment	SpO2 (oxygen saturation) is the percentage of oxygen in the blood. The fraction of inspired oxygen (FiO2) is the concentration of oxygen a person inhales.	baseline to 2 days after initiation of voxelotor treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SpO2/FiO2 (S/F) Ratio From Baseline to 5 Days After Initiation of Voxelotor Treatment	SpO2 (oxygen saturation) is the percentage of oxygen in the blood. The fraction of inspired oxygen (FiO2) is the concentration of oxygen a person inhales.	baseline to 5 days after initiation of voxelotor treatment

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Ian Welsby, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2022
• Primary Completion (Actual): June 28, 2023
• Study Completion (Actual): July 4, 2023

Study Registration Dates

• First Submitted: March 11, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 21, 2022

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: June 28, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Wounds and Injuries; Thoracic Injuries; Lung Diseases; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: Pro00109353

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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