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Voxelotor for Improving Oxygen Saturation in Adults (Voxelotor)

Primary Purpose

Acute Lung Injury, End Stage Lung Disease

Status

Suspended

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Voxelotor

About this trial

This is an interventional treatment trial for Acute Lung Injury

Eligibility Criteria

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

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.

Sites / Locations

Duke University Health System

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Voxelotor Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in S/F ratio from baseline to 2 days after initiation of voxelotor treatment

Median S/F value on baseline along with median S/F value on Day 2 after voxelotor treatment initiation will be used for ratio.

Secondary Outcome Measures

Change in S/F ratio from baseline to 5 days after initiation of voxelotor treatment

Median S/F value on baseline along with median S/F value on Day 5 after voxelotor treatment initiation will be used for ratio.

Full Information

NCT ID

NCT05289570

First Posted

March 11, 2022

Last Updated

October 6, 2023

Sponsor

Duke University

1. Study Identification

Unique Protocol Identification Number

NCT05289570

Brief Title

Voxelotor for Improving Oxygen Saturation in Adults

Acronym

Voxelotor

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Suspended

Why Stopped

Pending Protocol amendment, enrollment is on hold. There are no active subjects currently.

Study Start Date

May 3, 2022 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Duke University

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

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.

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.

6. Conditions and Keywords

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

Acute Lung Injury, End Stage Lung Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Voxelotor Arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Voxelotor

Other Intervention Name(s)

Oxbryta®

Intervention Description

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).

Primary Outcome Measure Information:

Title

Change in S/F ratio from baseline to 2 days after initiation of voxelotor treatment

Description

Median S/F value on baseline along with median S/F value on Day 2 after voxelotor treatment initiation will be used for ratio.

Time Frame

baseline to 2 days after initiation of voxelotor treatment

Secondary Outcome Measure Information:

Title

Change in S/F ratio from baseline to 5 days after initiation of voxelotor treatment

Description

Median S/F value on baseline along with median S/F value on Day 5 after voxelotor treatment initiation will be used for ratio.

Time Frame

baseline to 5 days after initiation of voxelotor treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ian Welsby

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke University Health System

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Voxelotor for Improving Oxygen Saturation in Adults

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