MN4000 for Treatment of CF and MND Patients in the Home Setting

A Pilot Study to Evaluate the Use of the MN4000 for Treatment of Cystic Fibrosis (CF) and Motor Neuron Disease (MND) Patients in the Home Setting

The study was a non-randomized open label pilot study. It was an observational design conducted at one (1) site in the US. All enrolled subjects received treatment with the MN4000. This pilot study evaluated subject satisfaction with the therapy and adherence to the therapy during the 90-day treatment period, and also collected clinical outcome data. Outcomes were assessed before, during and after the MN4000 treatment period.

The study was a non-randomized open label pilot study. It was an observational design conducted at one (1) site in the US. All enrolled subjects received treatment with the MN4000. This pilot study evaluated subject satisfaction with the therapy and adherence to the therapy during the 90-day treatment period, and also collected clinical outcome data. Outcomes were assessed before, during and after the MN4000 treatment period. The study did not include a control group. This pilot study was designed to provide initial information that could inform decisions for future larger-scale studies. Ten (10) patients total were enrolled from CF and NMD clinics. Eligible subjects were adult patients who were able to perform MN4000 therapy using a mouthpiece and who met all inclusion and none of the exclusion criteria. All patients received therapy with the MN4000 following the labeled instructions for the device. The MN4000 is an airway clearance and lung expansion therapy device that has been cleared to market by the FDA as The MetaNeb® System for Homecare environment, for clearance of pulmonary secretions and for treatment or prevention of pulmonary atelectasis. It is a Class II device, cleared to market on March 17, 2016 under premarket notification 510(k) K151689 as The MetaNeb® 4 System with application for homecare environment. It is commercially marketed as the MN4000. The device consists of a pneumatic compressor and an air pulse generator that delivers CHFO and CPEP to; facilitate clearance of mucous from the lungs; provide lung expansion therapy and; enhance delivery of aerosol therapy. This "triple" mode device can provide aerosol therapy while alternating between CPEP for lung expansion and CHFO for airway clearance. Supplemental oxygen therapy may also be delivered when used with compressed oxygen. The MN4000 has three therapy modes: CHFO (Continuous High Frequency Oscillation) - delivers aerosol therapy while providing oscillating pressure pulses to the airway CPEP (Continuous Positive Expiratory Pressure) - delivers aerosol therapy while providing continuous positive pressure to help hold open and expand the airways Aerosol - for delivery of aerosol only. In this mode, CHFO and CPEP are not available After assessing baseline status, therapy with the MN4000 was introduced and incorporated into the daily home respiratory care treatment regimen for all patients. Other airway clearance and/or lung expansion therapies were not to be performed during the three-month study period. The treatment regimen for other respiratory care modalities (e.g. aerosolized medications) was that which was prescribed by the patient's health care team in the routine standard care of each patient. During the three-month follow-up period, adherence to the daily prescribed therapy regimen was assessed. Subjects/caregivers were asked to provide adherence information for each day during the 90-day study period. Documentation of efficacy and safety Variables was completed by study staff at the time of occurrence, from review of the patient's medical records and from scores and rankings for questionnaires.

Patients with CF and MND who required regular home airway clearance therapy were enrolled to use the Metaneb device in the home setting. The MN4000 is an airway clearance and lung expansion therapy device that has been cleared to market by the FDA as The MetaNeb® System for Homecare environment, for clearance of pulmonary secretions and for treatment or prevention of pulmonary atelectasis. It is a Class II device, cleared to market on March 17, 2016 under premarket notification 510(k) K151689 as The MetaNeb® 4 System with application for homecare environment.

Patients who required regular home airway clearance therapy were enrolled in the study and were prescribed therapy with the MN4000. Adherence to the prescribed therapy regimen and patient/caregiver satisfaction with the therapy was assessed. Pulmonary function, was assessed for each subject at baseline, after 1 month and after 3 months of home therapy. Results from the therapy period was compared to the baseline period, during which the subject received their regular airway clearance regimen. Airway Clearance Satisfaction surveys were conducted at baseline, after 1 month, and after 3 months of therapy. Results from the MN4000 therapy period were compared to the baseline period, during which the subject received their regular regimen

The primary efficacy variable was patient and/or caregiver satisfaction with therapy, as evaluated using a Therapy Use Rating Scale questionnaire. The Therapy Use Rating Scale is an assessment of patient/caregiver satisfaction with the therapy and their subjective assessment of the benefit of the therapy. This was assessed by a 5 point likert scale assessing effectiveness, ease of use and likelihood to continue therapy with 5 representing positive responses and 1, negative.

Evidenced by feedback on adherence to therapy. Use of the MN4000 was evaluated, collecting daily treatment usage information from study subjects and/or caregivers to determine the level of adherence to the prescribed therapy regimen. A self reporting tool has been developed for the study assessing adherence to duration of individual prescribed treatment time and overall study duration.

MND patients only. MND patients only. The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) is an instrument for evaluating the functional status of patients with Amyotrophic Lateral Sclerosis. It can be used to monitor functional change in a patient over time. It contains 10 distinct measures: Speech Salivation Swallowing Handwriting Cutting food and handling utensils (with or without gastrostomy) Dressing and hygiene turning in bed and adjusting bed clothes Walking Breathing Climbing stairs These 10 parameters are scored on a scale of 0-4, based on the patients' ability to perform tasks. The minimum score is 0 and maximum 40.The higher the score the more function is retained.

CF patients only. The Cystic Fibrosis Questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF) > or = 14 years, consisting of 44 items on 12 generic and disease-specific scales. It offers 5 distinct 4-point Likert scales (e.g., always/often/ sometime/never). Scores for each HRQoL domain; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health.

Hospitalization and/or antibiotics for respiratory infection or complication. Exacerbations of pulmonary disease were defined as respiratory infections that resulted in requirement for hospitalization and/or antibiotics to treat the respiratory infection or complication. Hospitalizations that are part of routine care (e.g. hospital admissions for annual "tune-up") or antibiotics that are part of the regular treatment regimen were not documented as exacerbations. Occurence of exarcerbation related hospitalization OR the necessity of a prescription for antibiotics qualify as worsening disease.

FEV1: The forced expiratory volume-one second is the total volume of air a patient exhales in the first second during maximal effort. Normal range is >80%. Decreasing percentage is associated with worsening / Severe disease

The functional vital capacity is the total volume of air a patient exhales for the total duration of the test during maximal effort. Normal range is >80%. Decreasing percentage is associated with worsening / Severe disease

The percentage of the FVC expired in one second Results are given in both raw data (litres, litres per second) and % predicted-the test result as a percent of the "predicted values" for the patients of similar characteristics. Results over 80% are considered normal.

Slow Vital Capacity displays the volume of gas measured on a complete expiration after a maximal inspiration without forced or rapid effort. Useful measurement when FVC is reduced and airway obstruction is present. educed SVC is associated with worsening respiratory disease

SpO2 stands for peripheral capillary oxygen saturation, an estimate of the amount of oxygen in the blood. Low SPO2 is associated with worsening respiratory function.

Maximal inspiratory pressure (MIP) is a measure of the strength of inspiratory muscles, primarily the diaphragm, and allows for the assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. Reduction in MIP is asociated with worsening neuromuscular status and poor ability to cough.

The Peak Cough Flow is the maximum air flow generated during a cough. Decreasing air flow generated is associated with weakening neuromuscular status and associated poor cough impulse

Inclusion Criteria: Documented diagnosis of CF or MND Age > 18 years Signed informed consent Exclusion Criteria: Requirement for continuous mechanical ventilation Anticipated requirement for hospitalization within the next three months History of pneumothorax within past 6 months History of hemoptysis requiring embolization within past 12 months Inability to perform MN4000 therapy using a mouthpiece (e.g. inability to create adequate mouth seal) Inability to perform MN4000 therapy as directed Inability or unwillingness to complete study visits or provide follow-up data as required by the study protocol