JXR MEDI MIRS myAirvo3 High Flow Nasal Therapy

Parallel-group, prospective, randomized, controlled phase III trial of home High flow Nasal Therapy (HFNT) via myAirvo 3 plus usual COPD medical care vs. usual COPD medical care, for at least 1 year and up to two years in 642 GOLD Grade D, Stages II-IV patients with moderate to very severe COPD at risk for moderate and severe exacerbations with a prior history of severe exacerbation requiring hospitalization within the past 6 weeks.

Objectives:

Primary Objective: To determine if Hfnt delivered by myAirvo 3 increases the time to first moderate exacerbation orsevere exacerbation or all-cause mortality in patients with moderate to very severe COPD

Secondary Objectives:

To determine if HFNT delivered by myAirvo 3

1. increases the time to first severe exacerbation

2. increases the time to first exacerbation (moderate or severe)

3. reduces severe exacerbation frequency

4. reduces moderate and severe exacerbation frequency

5. reduces hospitalization duration

6. improves quality of life

7. reduces dyspnea

8. reduces PCO2

9. is safe and well tolerated

10. determine if any of the objectives are related to duration of daily HFNT use

11. Assess cost effectiveness of HFNT use

Exploratory objectives:

Develop objective definitions of exacerbations of differing levels of severity based on myAirvo 3 device or electronic diary collected measures of heart rate, respiratory rate, oxygen saturation, and dyspnea measured by modified visual analog score.

Endpoints: Primary Endpoint: The time to first moderate or severe exacerbation or all-cause mortality.

Primary Safety Endpoint: All data on adverse events, including reported to be not, possibly, probably, or definitely related to the use of myAirvo 3 device.

Secondary Endpoints:

• Rate of severe exacerbation, rate of moderate and severe exacerbations,

• Time to moderate exacerbation, time to severe exacerbation, time to moderate or severe exacerbation

• Hospitalization durations, from per visit data

• Quality of life by St George's Respiratory Questionnaire and SF-12

• Dyspnea, calculated mMRC and TDI over time

• Hours of daily HFNT use

• Impact of hours of daily HFNT use on any outcome

• PCO2

• Assess patient phenotype most likely to benefit from HFNT.

• Assess cost effectiveness of HFNT use

Exploratory endpoints:

• Development of objective definitions of exacerbations of differing levels of severity based on myAirvo 3 device or electronic diary collected measures of heart rate, respiratory rate, oxygen saturation, and dyspnea measured by modified visual analog score.

• HFNT settings (flow rate and temperature)

To be eligible to participate in this study, an individual must meet all the following

Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged 30 years or greater

4. FEV1/FVC of < 70% and an FEV1 of < 80% (GOLD stages II * IV, Grade E) • Spirometry performed during the screening visit will be used to confirm GOLD stage. A prior spirometric test within the past 6 months can be substituted if available.

5. MRC ≥ 2 or CAT ≥ 10

6. Former smokers or current smokers and never-smokers are eligible for study inclusion • Current smokers must refrain from smoking when using supplemental oxygen or the myAirvo-3 device

7. History of a severe COPD exacerbation requiring hospitalization in the previous six weeks

8. COPD in a stable state after hospitalization defined as:

   • Clinically stable condition and have had no parenteral therapy for 24 hours.

   • Inhaled bronchodilators are required less than four-hourly.

   • Oxygen delivery has ceased for 24 hours (unless home oxygen is indicated).

   • If previously able, the patient is ambulating safely and independently, and performing activities of daily living.

   • The patient can eat and sleep without significant episodes of dyspnea.

   • The patient or caregiver understands and can administer medications.

   • Follow-up and home care arrangements (e.g., home oxygen, homecare, Meals on Wheels, community nurse, allied health, GP, specialist) have been completed.

9. Willing to adhere to the daily use of the myAirvo 3 regimen for at least 8 hours each day preferably at night following being shown and using the device

10. Willing to record daily symptoms and pulse oximetry and heart rate on daily basis

11. For females of reproductive potential: use of highly effective contraception for at

least 1 month prior to screening and agreement to use such a method during study

participation

Highly effective contraception is defined as:

• A tubal ligation:

• An approved hormonal contraceptive such as oral contraceptives, emergency contraception used as directed, patches, implants, injections, rings or intrauterine devices

1. Able to read and communicate in English

2. Have a home environment suitable for myAirvo 3 use.

3. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study

duration * refraining from smoking while receiving supplemental oxygen or the

myAirvo-3 device

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation

In this study:

1. Current self-reported chronic use of positive airway pressure (PAP) therapy; continuous positive airway pressure (CPAP), or non-invasive positive pressure ventilation (NPPV)

2. A STOPBang Questionnaire score > 5*

3. Pregnancy or lactation

4. Treatment with another investigational drug or other intervention within the previous 30 days

5. Life expectancy less than 12 months due to COPD or other comorbid condition.

6. Recent upper airway surgery (within the previous month)

7. Recent head or neck trauma (within the previous month)

8. Inability to tolerate nasal prongs

9. Requirement of oxygen greater than 15 L/min

   • subjects with a STOPBang questionnaire score of > 5 may be eligible if a recent sleep study (within the previous 3 months) shows the absence of obstructive sleep apnea or the subject has, or is at risk of OSA, but refuses to use an OSA device and all other eligibility criteria are met.