Afrezza® INHALE-1 Study in Pediatrics

Study Overview
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Brief Summary
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INHALE-1 is a Phase 3, open-label, randomized clinical study evaluating the efficacy and safety of Afrezza in combination with a basal insulin (i.e., the Afrezza group) versus insulin aspart, insulin lispro or insulin glulisine in combination with a basal insulin (i.e., the Rapid-acting Insulin Analog [RAA] injection group) in pediatric subjects with type 1 or type 2 diabetes mellitus. Following 26 weeks of randomized treatment (i.e., Afrezza or RAA injection combined with a basal insulin), all subjects will enter a treatment extension where subjects will receive Afrezza until Week 52. The purpose of the treatment extension is to assess safety and efficacy with continued use of Afrezza. Pediatric subjects ≥4 and <18 years of age will be enrolled in this study. Subjects will be randomly assigned in a 1:1 ratio to either the Afrezza group or the RAA injection group. The study is composed of: Up to 5-week screening/run-in period 26 week randomized treatment period 26-week treatment extension 4-week follow-up period

Official Title
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INHALE-1: A 26-week Primary Treatment Phase, With 26-week Extension, Open-label, Randomized Clinical Trial Evaluating the Efficacy and Safety of Afrezza® Versus Rapid-acting Insulin Analog Injections, Both in Combination With a Basal Insulin, in Pediatric Subjects With Type 1 or Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Biological: Afrezza
* Biological: Rapid-acting Insulin Analog
* Biological: Basal Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Assent from the pediatric subject, as appropriate, and fully informed consent from the parent(s) or legal guardian, as required by both state and federal laws and the local Institutional Review Board (IRB) Subjects ≥4 and <18 years of age Clinical diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) per the Investigator and have been using insulin for at least 6 months for T1DM, or at least 3 months for T2DM Treatment with basal-bolus insulin therapy delivered by multiple daily injections for at least 2 weeks Bolus insulins are restricted to the RAAs insulin lispro, insulin aspart or insulin glulisine, including biosimilar products Basal insulins are restricted to insulin glargine, insulin degludec or insulin detemir, including biosimilar products Access to stable WiFi connection HbA1c ≥7.0% and ≤11% Average prandial dose of insulin ≥2 units per meal Utilized CGM for ≥70% of the time over a consecutive 14-day period preceding randomization Exclusion Criteria: History of recent blood transfusions (within previous 3 months), hemoglobinopathies, or any other conditions that affect HbA1c measurements Recent history of asthma (defined as using any medications to treat within the last year), any other clinically important pulmonary disease (e.g., cystic fibrosis or bronchopulmonary dysplasia), or significant congenital or acquired cardiopulmonary disease History of serious complications of diabetes (e.g., active proliferative retinopathy or symptomatic autonomic neuropathy), or likely need for specific treatment for diabetic retinopathy (laser photocoagulation, vitrectomy, other) in the next year FEV1 and FEV1/forced vital capacity (FVC) ≤80% of predicted Global Lung Function Initiative (GLI) value Inability to achieve an acceptable FEV1 and FVC reading for subjects ≥8 years of age would make the subject ineligible For subjects <8 years of age who are unable to achieve an acceptable FVC reading, FEV1 only may be assessed; inability to achieve an acceptable FEV1 would make the subject ineligible Respiratory tract infection within 14 days before screening (subject may return 14 days after resolution of symptoms for rescreening) Inability or unwillingness to perform study procedures Exposure to any investigational product(s), including drugs or devices, in the past 30 days Any disease other than diabetes or exposure to any medication that, in the judgment of the Investigator, may impact glucose metabolism and current or anticipated acute uses of glucocorticoids or weight loss medications, with the exception of metformin and/or GLP-1 agonists (if GLP-1 agonists used for at least the 3 months prior to enrollment) in subjects with T2DM Use of antiadrenergic drugs (e.g., clonidine) Any concurrent illness (other than diabetes mellitus) not controlled by a stable therapeutic regimen Current uncontrolled eating disorder (e.g., anorexia or bulimia nervosa) Current drug or alcohol abuse or a history of drug or alcohol abuse that, in the opinion of the Investigator or the Sponsor, would make the subject an unsuitable candidate for participation in the study Smoking (includes cigarettes, cigars, pipes, marijuana, and vaping devices) for the preceding 6 months and/or positive urine cotinine test Female subject who is pregnant, breast-feeding, intends to become pregnant, or is of child-bearing potential, sexually active and not using adequate contraceptive methods as required by local regulation or practice An event of severe hypoglycemia, as judged by the Investigator, within the last 90 days prior to screening An episode of DKA requiring hospitalization within the last 90 days prior to screening

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afrezza (Technosphere Insulin) + Basal Insulin<br>Individualized dose of Afrezza (Technosphere Insulin) for each patient before each meal (breakfast, lunch, and dinner) for 26 weeks. Individualized basal insulin (insulin degludec, insulin glargine or insulin detemir) for each patient. | Biological: Afrezza<br>* Pharmaceutical form: powder Route of administration: inhalation<br>* Other names: Technosphere Insulin;Biological: Basal Insulin<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: Levemir®;|
| Active Comparator: RAA Injection + Basal Insulin<br>Individualized dose of RAA injection (insulin aspart, insulin lispro or insulin glulisine) for each patient for 26 weeks. Individualized basal insulin (insulin degludec, insulin glargine or insulin detemir) for each patient. | Biological: Rapid-acting Insulin Analog<br>* Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous<br>* Other names: Apidra®;Biological: Basal Insulin<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: Levemir®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change in HbA1c from baseline to Week 26, for noninferiority assessment | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) | Change in FPG from baseline to Week 26, for superiority assessment | 26 weeks | 
| Event rate of pooled level 2 and level 3 hypoglycemia | Event rate of pooled level 2 and level 3 hypoglycemia (SMBG < 54 mg/dL and/or severe hypoglycemic events reported on the adverse event CRF) during the 26 -week randomized treatment period, for superiority assessment. | 26 weeks | 
| Change in HbA1c | Change in HbA1c from baseline to Week 26, for superiority assessment | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Insulin, Inhaled, Afrezza, Technosphere, Pediatric